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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.05 - LIBRETTO-431: Selpercatinib in Treatment-Naïve Patients with RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC). (ID 807)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Selpercatinib (LOXO-292) is a highly selective and potent inhibitor of RET signaling. In the LIBRETTO-001 Phase I/II trial, selpercatinib treatment resulted in a 64% objective response rate (ORR) (95% confidence interval [CI]: 54-73%) in the registration dataset (n=105) of patients with RET+ NSCLC who previously received platinum-based chemotherapy and an 85% ORR (95% CI: 70-94%) in treatment-naïve patients with RET+ NSCLC (n=39). Although the duration of response (DOR) and progression free-survival (PFS) were not yet mature in treatment-naïve patients, in patients who previously received chemotherapy, the median DOR was 18 months (95% CI: 12-not estimable [NE]), median PFS was 17.5 months (95% CI: 12-NE), and CNS ORR per RECIST 1.1 was 91% (95% CI: 59-100%) (n=10/11). The most common adverse reactions included dry mouth (39%), diarrhea (37%), hypertension (35%), and fatigue (35%). The majority of adverse reactions were Grade 1 or Grade 2. The most common lab abnormality was increased alanine aminotransferase (ALT) (51%)/aspartate transaminase (AST) (45%). A total of 5% of patients discontinued due to an adverse reaction.

      The LIBRETTO-431 trial, is a global, open-label, randomized, controlled, Phase 3 trial evaluating selpercatinib vs platinum-based and pemetrexed treatment +/- pembrolizumab in treatment-naïve patients with locally advanced or metastatic RET+ non-squamous NSCLC (NCT04194944).

      Methods

      Patients will be randomized to receive selpercatinib 160 mg BID in 3-week cycles (Arm A) or pemetrexed (500 mg/m2 IV) in 3-week cycles plus investigator’s choice of carboplatin (AUC 5) or cisplatin (75 mg/m2 IV) for 4 cycles (Arm B). For patients in Arm B, at the investigator’s discretion, pembrolizumab (200 mg IV) may also be given for up to 35 cycles and patients may receive maintenance pemetrexed +/- pembrolizumab. Crossover to selpercatinib is allowed for Arm B patients who have disease progression. Treatment will be discontinued for progressive disease, unacceptable toxicity, decision to withdraw or death. Stratification factors include geography: East Asian versus non-East Asian, brain metastases: presence versus absence, and intended treatment if randomized to Arm B: +/- pembrolizumab. RET status may be determined in tumor (by PCR or NGS) or in blood (by NGS) using a qualified local test or a Lilly-enabled regional test. Key eligibility criteria include age ≥18 years; treatment-naïve; non-squamous Stage IIIB-IIIC not suitable for surgery/radiation therapy or Stage IV NSCLC; measurable disease by RECIST 1.1; ECOG performance status 0-2. Key exclusion criteria include presence of other known oncogenic drivers and symptomatic central nervous system metastases. Tumor assessments will be performed until progressive disease, the start of a new anticancer treatment, death or study completion. The co-primary endpoint, PFS by independent review in intent-to-treat (ITT) patients with pembrolizumab (if assigned to control), will act as a gatekeeper to the co-primary endpoint PFS by independent review in the ITT population. Secondary endpoints include investigator assessed PFS, ORR/DOR, intracranial ORR/DOR, overall survival, time to deterioration in pulmonary symptoms, progression after the next line of therapy, RET fusion status: local versus central, and safety/tolerability. The study was initiated in March 2020 and enrollment is ongoing.

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      FP14.11 - Icotinib versus Chemotherapy as Adjuvant Treatment for Stage II–IIIA EGFR-Mutant NSCLC (EVIDENCE): A Randomized, Open-Label, Phase 3 Study (ID 3605)

      00:00 - 00:00  |  Presenting Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Recent studies have shown significant benefits of EGFR tyrosine kinase inhibitors in the adjuvant setting for patients with EGFR-mutant stage IB–IIIA resected NSCLC. This study aimed to compare the efficacy and safety of icotinib with standard chemotherapy in adjuvant setting in patients with EGFR mutant stage II-IIIA NSCLC.

      Methods

      In this randomized, open-label, phase 3 study, eligible patients aged 18-70 years who had completely resected (R0), stage II-IIIA EGFR-mutant NSCLC (in-frame deletion in exon 19 or Leu858Arg point mutation in exon 21) were randomly assigned, in a 1:1 ratio, to receive either adjuvant icotinib (125 mg thrice daily administered orally for 2 years) or four-cycle chemotherapy (cisplatin plus vinorelbine, or cisplatin plus pemetrexed for non-squamous carcinoma). Patients were stratified by clinical stage (II vs IIIA), EGFR mutation type (exon 19 vs 21), and resection methods (lobectomy vs pneumonectomy). The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety.

      Results

      A total of 365 patients were screened, and 322 patients (161 for each arm) were enrolled from 29 centers across China between June 2015 and July 2019. Thirty-nine patients had major protocol violations and were excluded, leaving 283 patients in full analysis set (151 in icotinib arm and 132 in chemotherapy arm, respectively). 53% and 47% of patients had an EGFR mutation of 19 Del and 21 L858R, respectively. At the data cutoff (March 31, 2020) for the pre-specified interim analysis, 98 out of 196 (50%) events were recorded with a median follow-up of 24.9 months (95% CI, 22.1 to 28.8). In full analysis population, the median DFS (mDFS) was 47.0 months (95% CI, 36.44 to not reached) in the icotinib group and 22.1 months (95% CI, 16.8 to 30.4) in the chemotherapy group (stratified hazard ratio=0.36; 95% CI, 0.24 to 0.55; P < 0.0001). Analyses of DFS based on stratification criteria and vital demographic and prognostic factors showed consistent benefits of icotinib treatment across subgroups. The 3-year DFS was 63.9% in the icotinib group and 32.5% in the chemotherapy group. It is immature to perform OS analysis with14 (9.3%) patients in the icotinib group and 14 (10.6%) patients in the chemotherapy group died, respectively. Adverse events of grade 3 or 4 were observed in 10.9% of the patients in the icotinib group and 61.2% in the chemotherapy group. Treatment-related serious adverse events occurred in 2 (1.3%) patients in the icotinib group and 19 (13.7%) patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in each group.

      Conclusion

      Adjuvant icotinib significantly improved DFS in patients with EGFR mutant stage II-IIIA NSCLC compared with standard chemotherapy and demonstrated a better tolerability profile. Icotinib can provide a new treatment option for stage II-IIIA NSCLC patients with activating EGFR mutation.

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    IS15 - Industry Symposium Sponsored by Amoy: Lung Cancer Biomarker Panel Testing (ID 292)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS15.04 - Large Scale Real World Study on Rare Actionable Targets in Chinese NSCLC (ID 4373)

      13:00 - 14:00  |  Presenting Author(s): Caicun Zhou

      • Abstract

      Abstract not provided

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    JICC01 - Joint IASLC-CAALC-CSCO Session: The Truth and Myth of Oral Anti-VEGFR Inhibitors for Advance NSCLC (ID 276)

    • Event: WCLC 2020
    • Type: Workshop
    • Track: N.A.
    • Presentations: 2
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      JICC01.04 - Chair (ID 4263)

      07:00 - 09:00  |  Presenting Author(s): Caicun Zhou

      • Abstract

      Abstract not provided

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      JICC01.11 - Icotinib versus Chemotherapy as Adjuvant Treatment for Stage II–IIIA EGFR-Mutant NSCLC (EVIDENCE): A Randomized, Open-Label, Phase 3 Study (ID 4275)

      07:00 - 09:00  |  Presenting Author(s): Caicun Zhou

      • Abstract

      Introduction
      Recent studies have shown significant benefits of EGFR tyrosine kinase inhibitors in the adjuvant setting for patients with EGFR-mutant stage IB–IIIA resected NSCLC. This study aimed to compare the efficacy and safety of icotinib with standard chemotherapy in adjuvant setting in patients with EGFR mutant stage II-IIIA NSCLC. Methods
      In this randomized, open-label, phase 3 study, eligible patients aged 18-70 years who had completely resected (R0), stage II-IIIA EGFR-mutant NSCLC (in-frame deletion in exon 19 or Leu858Arg point mutation in exon 21) were randomly assigned, in a 1:1 ratio, to receive either adjuvant icotinib (125 mg thrice daily administered orally for 2 years) or four-cycle chemotherapy (cisplatin plus vinorelbine, or cisplatin plus pemetrexed for non-squamous carcinoma). Patients were stratified by clinical stage (II vs IIIA), EGFR mutation type (exon 19 vs 21), and resection methods (lobectomy vs pneumonectomy). The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. Results
      A total of 365 patients were screened, and 322 patients (161 for each arm) were enrolled from 29 centers across China between June 2015 and July 2019. Thirty-nine patients had major protocol violations and were excluded, leaving 283 patients in full analysis set (151 in icotinib arm and 132 in chemotherapy arm, respectively). 53% and 47% of patients had an EGFR mutation of 19 Del and 21 L858R, respectively. At the data cutoff (March 31, 2020) for the pre-specified interim analysis, 98 out of 196 (50%) events were recorded with a median follow-up of 24.9 months (95% CI, 22.1 to 28.8). In full analysis population, the median DFS (mDFS) was 47.0 months (95% CI, 36.44 to not reached) in the icotinib group and 22.1 months (95% CI, 16.8 to 30.4) in the chemotherapy group (stratified hazard ratio=0.36; 95% CI, 0.24 to 0.55; P < 0.0001). Analyses of DFS based on stratification criteria and vital demographic and prognostic factors showed consistent benefits of icotinib treatment across subgroups. The 3-year DFS was 63.9% in the icotinib group and 32.5% in the chemotherapy group. It is immature to perform OS analysis with14 (9.3%) patients in the icotinib group and 14 (10.6%) patients in the chemotherapy group died, respectively. Adverse events of grade 3 or 4 were observed in 10.9% of the patients in the icotinib group and 61.2% in the chemotherapy group. Treatment-related serious adverse events occurred in 2 (1.3%) patients in the icotinib group and 19 (13.7%) patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in each group. Conclusion
      Adjuvant icotinib significantly improved DFS in patients with EGFR mutant stage II-IIIA NSCLC compared with standard chemotherapy and demonstrated a better tolerability profile. Icotinib can provide a new treatment option for stage II-IIIA NSCLC patients with activating EGFR mutation.

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    MA01 - Novel Systemic Treatment in NSCLC (ID 102)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
    • Presentations: 1
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      MA01.04 - A Randomized Study Comparing Cisplatin/Paclitaxel Liposome vs Cisplatin/Gemcitabine in Chemonaive, Advanced Squamous NSCLC (ID 1225)

      11:45 - 12:45  |  Presenting Author(s): Caicun Zhou

      • Abstract

      Introduction

      Platinum-based chemotherapy is still the backbone of advanced squamous non–small-cell lung cancer (NSCLC). Paclitaxel (PTX) liposome is the only PTX liposomal formulation on the market for the treatment of lung, ovarian and breast cancer since 2006 in China. The purpose of this study was to compare the clinical efficacy and safety between PTX liposome/cisplatin and gemcitabine/cisplatin as first-line treatment of patients with staged IIIB/IV squamous NSCLC.

      Methods

      Eligible patients with chemo naive, advanced, squamous NSCLC were randomized to receive PTX liposome (175 mg/m2, on day 1) and cisplatin (75 mg/m2 on day 1, LP group) or gemcitabine (1,000 mg//m2, on day 1 and 8) and cisplatin (75 mg/m2 on day 1, GP group) intravenously, every 3 weeks for 4-6 cycles. Primary end point of the study was progression-free survival(PFS).

      Results

      A total of 540 patients from 34 centers of China were enrolled. Median age: 64.5 years; male/ female: 497(93.1%)/37(/6.9%); stage IIIB/IV: 177(33.1%)/357(66.9%) and ECOG PS 0/1: 87(16.3%)/447(83.7%). After a median follow-up of 15.4 months, PFS and overall survival were not different between LP and GP groups (median PFS 5.2 vs. 5.5 months, hazard ratio [HR] 1.03, P=0.5762; median OS 14.6 vs 12.5 months, HR 0.83, P=0.2147). Overall response rate was comparable between the 2 groups, 41.8% in LP group vs 45.9% in GP group. The most common adverse events (AEs) in the both groups were anemia, neutropenia, leukopenia and thrombocytopenia. AEs of grade 3 or higher occurred in 68.3% of the patients in the LP group and in 66.5% of the patients in the GP group. Grade 3 or higher anemia (31.2%, 84/269 vs. 14.3%, 38/265, P<0.0001) and thrombocytopenia (14.1%, 38/269 vs. 1.5%, 4/265, P<0.0001) were more frequent in the GP group, whereas grade 3 or higher neutropenia (35.5%, 94/265 vs. 28.3%, 76/269, P=0.0781) and leukopenia (23.4%, 62/265 vs. 19.0%, 51/269, P=0.2438) were more frequent in the LP group. Discontinuation of treatment due to AEs was more frequent in the GP group than in LP group (26.4% vs. 10.9%, P<0.0001).

      Conclusion

      The chemo-regimens, LP and GP produce comparable efficacy in terms of ORR, PFS and OS as 1st line therapy of advanced squamous NSCLC. But, LP is well tolerated and results in less frequent of anemia and thrombocytopenia and lower discontinuation of treatment in Chinese patients. So, LP is one of standard 1st line chemotherapy for advanced squamous NSCLC patients. (ClinicalTrials.gov number, NCT02996214)

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    MA13 - Tumor Biology: Focus on EGFR Mutation, DNA Repair and Tumor Microenvironment (ID 214)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
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      MA13.06 - Deciphering the Characterization of Tumor Microenvironment in EGFR-Mutated Non-Small Cell Lung Cancer (ID 3816)

      16:45 - 17:45  |  Author(s): Caicun Zhou

      • Abstract

      Introduction

      Anti-PD-1(L1) therapies appear to be less efficacious in NSCLC patients whose tumors have EGFR activating mutations, but the underlying mechanism is poorly understood.

      Methods

      An established computational approach (CIBERSORT) to gene expression profiles of 402 lung adenocarcinoma from TCGA database was applied to infer the proportions of 22 subsets of immune cells in EGFR mutated and wild-type tissue samples. Primary NSCLC resections and peripheral blood of advanced NSCLC patients with determined EGFR status were collected and analyzed the subtypes of immune cells and T cell function via flow cytometry. Pre-treatment and one-cycle of immunotherapy plasma levels of 10 cytokines were measured using Meso Scale Discovery (MSD) in patients treated with immunotherapy. Association between EGFR signaling pathway and IL-10 mRNA expression was analyzed via PCR and western blotting. In vitro re-stimulation model of human CD8+T cells isolated from peripheral blood was used to analyze the impact of different dose of IL-10 on T cells.

      Results

      EGFR-WT tumors were associated with higher proportions of CD8+T (p<0.001) cells and activated memory CD4+ T cells (p<0.001).Transcriptome profiling revealed that lymphocyte activation or functions markers were highly expressed in EGFR-WT tumor. In primary NSCLC resections, EGFR-MUT tumors had lower proportion of CD8+Ki67+T cells (p=0.003). Functional or activated subsets of CD8+T cells, such as CD38+HLA-DR+ and GranzymeB+Ki67+ were also significantly less infiltrated in EGFR-MUT tumors (p=0.016, p=0.013, respectively).CD39, which was recently reported as a novel marker to distinguish bystander TILs (CD39-CD8+) was highly expressed in EGFR-MUT tumors (p=0.012). Similarly, treatment-naïve advanced EGFR-WT patients also had higher percentage of CD8+T cells expressing CD39 in peripheral blood. In addition, CD8+CD39+T cells subset was associated with higher level of Ki67, GranzymeB+Ki67+, PD-1+Ki67+and CD38+HLA-DR+ compared with CD39-T cells. Intratumoral level of IFN-γ, IL-10, IL-1 β, IL-4 was significantly lower in EGFR-MUT tumors compared with WT tumors. To further investigate the role of CD8+T cells expression CD39 and 4 differentially expressing cytokines, we also obtained PBMC from advanced NSCLC patients who received anti-PD1 treatment. Only IL-10 and CD39 were associated with immunotherapy response. In vitro study, 7 tumor cell lines were cocultured with CD8+T cells isolated from healthy donors. CD39+expressing CD8+T cells were significantly increased in the presence of EGFR-WT cell lines than EGFR-MUT cell lines. Also, higher IL-10 was associated with increased proliferation, cytotoxicity of T cells and CD39 expression in dose-dependent manner. To investigate the association of EGFR signaling and IL-10 expression, we added gefitinib in EGFR mutated cell lines and EGF in EGFR-WT cell lines. IL-10 mRNA expression was significantly increased after blocking EGFR signaling pathway and decreased after reactivation of EGFR pathway.

      Conclusion

      Poor response to anti-PD-1 treatment in EGFR patients could be attributed to:1) non-inflammed TME with lower percentage of activated or functional T cell subsets; 2) the abundance of CD39– CD8+ T cells in EGFR-mutated patients. Additional IL-10 could possibly reinvigorate CD8+CD39+T cells to potential anti-PD1 efficacy in EGFR-mutated patients.

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    OA04 - New Data from Rare EGFR Alterations (ID 223)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
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      OA04.03 - Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations (ID 3186)

      11:45 - 12:45  |  Presenting Author(s): Caicun Zhou

      • Abstract

      Introduction

      Mobocertinib is a potent first-in-class tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (EGFRex20ins) mutations. We report first results from the EXCLAIM extension cohort of a phase 1/2 study (NCT02716116) and results in patients with EGFRex20ins-mutant NSCLC who received prior platinum-based therapy from the dose-escalation/expansion parts of the study and the EXCLAIM extension cohort.

      Methods

      This 3-part, open-label, multicenter study included dose-escalation/expansion cohorts and the EXCLAIM extension cohort. Data are presented for all patients treated in EXCLAIM (N=96) and for platinum-pretreated patients from the dose-escalation/expansion cohorts (n=28) and from EXCLAIM (n=86); all received mobocertinib 160 mg orally QD. Enrolled patients had locally advanced/metastatic EGFRex20ins NSCLC, ECOG performance status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease. The primary endpoint is confirmed ORR assessed by IRC per RECIST v1.1.

      Results

      In EXCLAIM, 96 patients were enrolled and treated; median age, 59 years [range: 27–80]; female, 65%; Asian, 69%; ≥2 prior systemic anticancer lines, 49% (range: 1–4). Median time on treatment was 6.5 months (range: 0–14). Confirmed ORR was 23% (22/96; 95% CI: 15%–33%) per IRC and 32% (95% CI: 23%–43%) per investigator; median DoR (Kaplan-Meier estimates) was not mature; median PFS was 7.3 months. See Table. In the analysis of platinum-pretreated patients (n=114), median age, 60 years [range: 27–84]; female, 66%; Asian, 60%; ≥2 prior systemic anticancer lines, 59% (range: 1–7). Median time on treatment was 7 months (range: 0–31); 38 patients (33%) remained on treatment as of 29-May-2020. Confirmed ORR was 26% (30/114; 95% CI: 19%–35%) per IRC and 35% (40/114; 26%–45%) per investigator. Median PFS was 7.3 months: 12-month PFS rate was 33% (95% CI: 21%–47%). Responses were observed among all prespecified subgroups, including Asian/non-Asian patients and those with/without baseline stable brain metastases. The most common treatment-related adverse events (TRAEs; ≥30%): diarrhea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%), and vomiting (30%); grade ≥3 TRAEs (≥5%): diarrhea (22%), anemia (5%), and dyspnea (5%). Nineteen patients (17%) discontinued due to AEs, most commonly diarrhea (4%) and nausea (4%). The safety profile observed in EXCLAIM was largely consistent with that observed in the platinum-pretreated population.

      table for submission.jpg

      Conclusion

      Mobocertinib demonstrated clinically meaningful benefit in previously treated patients with NSCLC and EGFRex20ins mutations, with a manageable safety profile.

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    P01 - Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics (ID 227)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Antibody Drug Conjugates, Novel Therapeutics and Cytotoxics
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P01.10 - Patients Experienced Pseudoprogression to Anti-PD-1/PD-L1 Inhibitor Have Better Response Than Those Without in Lung Cancer (ID 1774)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract

      Introduction

      Pseudoprogression present to be an atypical pattern of response for anti-PD-1/PD-L1 immunotherapy (IO) in lung cancer. It happens uncommon and we have limited knowledge about it.

      Methods

      Lung cancer patients treated with anti-PD-1/PD-L1 from May 2016 to October 2019 in Shanghai Pulmonary Hospital were retrospectively reviewed. Pseudoprogression was defined as progression from baseline and followed by response from peak. We analyzed incidence, time course, clinical characteristics, treatment and outcomes. Propensity Score Matching (PSM) was applied to adjust for potential confounding factors. Progression-free survival (PFS) was estimated with Kaplan-Meier method.

      Results

      Totally, 15 out of 449 pts were identified with pseudoprogression and one patient received re-biopsy for the pseudoprogressive lesion. All patients were male with a median age of 64 (range: 52-76), most (86.7%) were ever smokers,had histologic subtype of adenocarcinoma(n=8), squamous(n=5),NSCLC-NOS(n=1) and SCLC(n=1), and had stage IIIc (n=1), stage IV (n=14). Two pts were found with EGFR mutation (1with 19Del and 1 with G719X) and 1 pt was identified with KRAS mutation. The IO used were pembrolizumab (n=5), Atezolizumab(n=1) and domestic PD-1 inhibitors (SHR1210 n=3, BGB-A317 n=2, IBI308 n=2 and JS001 n=2). Eight pts treated with single agent, 5 with combination of chemotherapy, and 3 with combination of anti-angiogenesis. Three pts were used as first line, 8 as second line and 4 as third line. Pseudoprogression occurred at a median time of 9 weeks (range: 2-46), 13/15 of cases happened within six month, one in nine month and one in twelve month. Among them, 13 pts had enlarged primary lung lesions and 2 patients had enlarged bilateral pulmonary nodules, no pts had enlargement of distant metastatic lesions. The overall response rate is 40%, and disease control rate was 100%. After adjustment for pts’ age, gender, treatment line, combining therapy type with the PSM method, we found PFS is significantly longer in pseudoprogression cohorts than control cohorts: 9.6 month (95% CI:0-22.5) vs 4.2 month (95% CI:3.4-5.0), P=0.02. One SCLC patient received rebiopsy at the time of pesudoprogression showed obvious lymphocyte infiltration and no cancer cells.

      Conclusion

      Patients who experienced pseudoprogression with IO have obviously longer PFS than those without. Further studies in larger cohort are needed to confirm this finding.

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      P01.13 - Anti-PD1 Inhibitors Combined With Anti-Angiogenesis Showed Superior Efficacy in Control of Malignant Pleural Effusion for NSCLC (ID 2063)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract

      Introduction

      Malignant pleural effusion (MPE) is closely associated with patients' quality of life, and is not easy to control by chemotherapy and targeted therapy. This study aim to investigate efficacy of control of MPE in the era of immunotherapy (IO) and compare control rate with different treatment strategies.

      Methods

      NSCLC patients treated with anti-PD1 from May 2016 to October 2019 in Shanghai Pulmonary Hospital were retrospectively reviewed. MPE was defined as finding malignant cells in pleural fluid. Pleural effusion control rate (PECR) was defined as the percentage of patients whose MPE without re-accumulation for 8 weeks. Chi-Square test was used for comparing categorical variables. Kaplan Meier method was applied to compared progression-free survival (PFS).

      Results

      53 out of 449 patients with MPE were enrolled. Baseline characteristics were: men:67.9%; median age:63(33-76 years); ECOG PS 0-1:92.5%; ever smokers:67.9%; adenocarcinoma: 83% and 26.4% patients received 1st line treatment. Among them, 15 patients treated with anti-PD1 monotherapy, 8 pts with combination of multiple kinase inhibitor Apatinib, 30 pts with combination of chemotherapy (21 with pemetrexed/ platinum, 5 with nab-Paclitaxel, 3 with Docetaxel and 1 with Gemcitabine plus cisplatin). Overall response rate (ORR) and disease control rate (DCR) for targeted lesion were 18.9% and 75.5% respectively. PECR was 67.9% for MPE. At last follow-up, 40 patients experienced disease progression and 50% patients got re-accumulation of MPE. The PECR of Apatinib-combining group was higher than chemotherapy-combining group: 100% vs 66.7% (p=0.08), also higher than monotherapy group: 100% vs 53.3% (p=0.05). The difference is not statistically different due to small sample size. But the PECR in Apatinib-combining group is obviously higher than non Apatinib-combining group: 100% vs 62.2%, p=0.04. The PFS was 10.6 month (95%CI 3.64-17.56) versus 3.6 (95%CI 1.74-5.46) separately, p=0.01.

      Conclusion

      The combination of anti-PD1 with Apatinib demonstrates superior efficacy in controlling MPE for NSCLC patients. Large prospective studies are needed to confirm this finding.

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    P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 3
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P47.02 - CCL19 Associates with Inferior Prognosis in Patients with SCLC Through Promoting Invasion and Metastasis (ID 1739)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Small cell lung cancer(SCLC) is a systemic disease and majority have metastasis at the initial diagnosis. Therefore, better understanding of the molecular mechanisms underlying SCLC metastasis may potentially improve clinical outcome.

      Methods

      RNA-seq was used to identify the differential gene expression between primary SCLC lesions and paired metastatic lymph nodes. Function assays and Western blotting were carried out to investigate the mechanism of CCL19 promote metastasis. Co-incubation and flow cytometry used to detect the impact of CCL19 on CD8+T cells function. Plasma CCL19 was detected by ELISA. Kaplan–Meier was used to perform survival analysis in patients.

      Results

      Four chemokines(CCL19,CCL21,CCL8,CCR1) had significantly different expression between primary SCLC lesion and metastatic LN. CCL19 was chose for further investigation because its mRNA expression was significantly higher in four SCLC cell lines(H446, H69, H82, H196) than normal bronchial epithelial cell line(Beas-2b) when compared with other three chemokines. CCL19 silencing significantly inhibited SCLC cell migration, invasion, proliferation and angiogenesis abilities. Mechanistically, we identified CCL19 promoted SCLC metastasis by MAPK-ERK signaling pathways. Furthermore, tumor-derived CCL19 biologically inhibited the function of CD8+ T cells with lower percentage of CD8+Ki67+ and CD8+GZMB+ T cells, whereas percentage of CD8+PD1+ T cells increased. Moreover, plasma higher CCL19 concentration was associated with late lymph node metastasis(Training cohort p=0.044, Validation cohort p=0.020) and shorter overall survival(Training cohort p=0.040, Validation cohort p=0.047) in SCLC patients.figure1.jpgfigure2.jpg

      Conclusion

      CCL19 promoted tumor progression and metastasis through MAPK/ERK signaling pathways and inhibited the function of CD8+ T cells. Its expression was associated with metastasis and poor prognosis in patients with SCLC, suggesting CCL19 might be served as a potential target for SCLC.

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      P47.07 - Exploration of Aberrant Methylation Patterns in the Chemotherapy Insensitivity of Small Cell Lung Cancer (ID 3234)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Epigenetic alterations of specific genes are closely related to chemotherapeutic efficacy in various cancers. However, few comprehensive profiles of differentially methylated genes (DMGs) in small cell lung cancer (SCLC) were available.

      Methods

      In the study, Methylated DNA immunoprecipitation sequencing and RNA sequencing was employed to clinical small cell lung cancer (SCLC) patients. Then, we verified the therapeutic predictive effects of differentially methylated genes (DMGs) in 62 SCLC cell lines.

      Results

      Of 4552 DMGs which were selected (fold change ≥ 2, p<0.01) between chemo-sensitive and chemo-insensitive group, coding genes constituted the largest percentage (3873/4551, 85.08%), followed by lncRNAs (479/4551, 10.52%) and miRNAs (162/4552, 3.56%). Further, both two groups demonstrated two methylation peaks near transcription start site and transcription end site. Two lncRNA-miRNA-mRNA networks which based on genes that showed opposite results in genetic expression and epigenetic modifications suggested the extensive genome connection between chemotherapy efficacy-related non-coding RNAs (ncRNAs) and mRNAs (Figure 1). Combing four DMGs, including hsa-miR-34a, LINC00461, LINC01018, and LINC01484 could effectively predict first-line chemotherapy response in SCLC, indicating that they might play vital roles in SCLC chemotherapy insensitivity (Figure 2).

      figure 1.pngfigure2.png

      Conclusion

      In SCLC, multiple efficacy-related ncRNAs and mRNAs were modified by methylation. In addition, DMGs identified in our research might be served as predictors for chemotherapy effect and promising therapeutic targets to reverse drugs-insensitivity in SCLC. Further comprehensive studies of these findings are worthy of expecting.

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      P47.13 - Galectin-9, A Novel Prognostic Factor in Small Cell Lung Cancer (ID 1232)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      For small cell lung cancer (SCLC) therapy, immunotherapy might have unique advantages to some extent. Galectin-9 (Gal-9) palys an important role in anti-tumor immunity, while little is known of its function in SCLC.

      Methods

      By mean of immunohistochemistry (IHC), we tested the expression level of Gal-9 and other immune markers on both tumor cells and tumor-infiltrating lymphocytes (TILs) in 102 surgical-resected early stage SCLC clinical samples. On the basis of statistical analysis and machine learning results, the Gal-9-based immune risk score model was constructed and its predictive performance was evaluated. Then, we thoroughly explored the effects of Gal-9 and immune risk score on SCLC immune microenvironment and immune infiltration in different cohorts and platforms.

      Results

      In the SCLC cohort for IHC, the expression level of Gal-9 on TILs was statistically correlated with the levels of PD-1 (p=0.001), PD-L1 (p<0.001), CD3 (p<0.001), CD4 (p<0.001), CD8 (p<0.001), and FOXP3 (p=0.047). High Gal-9 protein expression on TILs indicated better recurrence-free survival (Figure 1;p=0.009). The immune risk score model which consisted of Gal-9 on TILs, CD4, and PD-L1 on TILs was established and validated so as to differentiate high- or low-risk SCLC patients. The prognostic predictive performance of immune risk score model was better than single immune biomarker (AUC 0.671 vs. 0.621-0.644). High Gal-9-related enrichment pathways in SCLC were enriched in immune system diseases and rheumatic disease. Furthermore, we found that SCLC patients with low immune risk score presented higher fractions of activated memory CD4 T cells than it of the high immune risk score cohort (Figure 2; p=0.048).

      1.png

      figure 2.png

      Conclusion

      Gal-9 is markedly related to tumor immune microenvironment and immune infiltration in SCLC. This study emphasized the predictive value and promising clinical applications of Gal-9 in SCLC.

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    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P76.07 - Metformin Enhances the Efficacy of EGFR-TKIs in Advanced Non-Small Cell Lung Cancer Patients With Type 2 Diabetes Mellitus (ID 897)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Lung cancer remains the leading cause of cancer-related mortality around the world. Despite epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) therapy have shown remarkable clinical efficacy in non-small cell lung cancer (NSCLC) patients, resistance is almost inevitable and is still a major obstacle. Studies have suggested that the prolonged use of metformin, a common oral anti-diabetes agent, also an IGF-1R inhibitor, is associated with survival benefits among NSCLC Type 2 diabetes mellitus (T2DM) patients. However, the clinical efficacy of metformin and EGFR-TKIs in combination, especially third-generation TKIs, on NSCLC patients with T790M mutation has not been well validated. Therefore, we retrospectively reviewed the effect of metformin use on the clinical efficacy of EGFR-TKIs in NSCLC patients with T2DM, and we also carried out in vitro experiment to demonstrate the effects of metformin in EGFR-TKI resistant cell lines in aspect of proliferation and apoptosis.

      Methods

      We retrospectively reviewed clinicopathological characteristics and response of NSCLC patients with type 2 diabetes mellitus (T2DM) who received EGFR-TKIs treatment. Therapeutic outcome including objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) of first-line EGFR-TKIs and second-line osimertinib were compare between patients received metformin and other anti-diabetes drugs. In addition, the effect of metformin on gefitinib-resistant cell line PC9R and osimertinib-resistant cell line PC9R/OR was examined in vitro using Cell Counting Kit-8, and apoptosis analysis, the IC 50, apoptosis rate and combination index (CI) was calculated.

      Results

      In fist-line EGFR-TKIs treatment, ORR in metformin use group was significantly higher (85.7% vs. 47.4%, p=0.001). The PFS1 and OS1 in metformin use group were significantly longer (21.6 months vs. 9.2 months, p =0.000; 48.4 months vs. 36.6 months, p =0.049). Further analysis revealed that metformin obviously prolonged the median PFS2 of osimertinib treatment among patients who progressed to prior line EGFR-TKIs with T790M. In vitro analysis, metformin showed synergistic interaction both with gefitinib in PC9R (CI=0.77) and with osimertinib in PC9R/OR (CI=0.77) in proliferation inhibition analysis. Metformin can also augment apoptosis effect of these TKI-resistant cells to EGFR-TKIs in vitro (p<0.05).

      figure 1.png

      Conclusion

      The results of our study suggest metformin use could be beneficial to NSCLC patients with T2DM treated with either first-line EGFR-TKIs or second-line osimertinib treatment.

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      P76.11 - Patients With Short PFS to EGFR-TKIs Predicted Better Response to Subsequent Anti-PD-1/PD-L1 Based Immunotherapy in EGFR Mutated NSCLC (ID 1032)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Several studies and meta-analysis have confirmed that non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) sensitive mutation can’t benefit from anti-PD1/PD-L1 monotherapy. Our previous study confirmed that anti-PD1/PD-L1 with chemotherapy have survival benefit in EGFR-TKI resistant patients. While which subgroup of EGFR mutated patients could benefit from anti-PD1/PD-L1 based treatment is not clear.

      Methods

      Advanced NSCLC patients harboring EGFR sensitive mutations (19DEL/L858R) after resistant to EGFR-TKIs and received anti-PD1/PD-L1 based treatment any lines were retrospectively analyzed from January 2016 to June 2019. Clinical characteristics, progress-free-survival (PFS), objective response rate (ORR) and treatment-related side effects were recorded for all patients.

      Results

      Fifty-eight patients with EGFR sensitive mutation treated with PD-1/PD-L1 based treatment were enrolled. The median age was 58.8 years old. Male accounted for 56.9%. 84.5% were never smoker, 48.3% were 19DEL and 51.7% were L858R. 93.1% were stage IV. Among them, 43.1% of patients received ICIs in second line. Most of them (52/58, 89.7%) received combination treatment including 48 of them combined with chemotherapy and 4 of them combined with antiangiogenic therapy. The median PFS of previous EGFR-TKIs treatment (TKI-PFS) and anti-PD-1/PD-L1 based immunotherapy (IO-PFS) was 10.4 months and 5.5 months respectively. Correlation analysis showed that the TKI-PFS had an obvious negative relevance with the corresponding IO-PFS. Then we divided patients into long and short group with TKI-PFS cutoff at 10 months. Uni- and multivariate analysis demonstrated that TKI-PFS less than 10 months was independently associated with better clinical outcomes from subsequent immunotherapy. Kaplan-Meier analysis showed that patients with TKI-PFS < 10 months had a significantly longer IO-PFS than those ≥ 10 months, with median IO-PFS of 15.1 versus 3.8 months respectively (HR, 0.27, p=0.003). The ORR of immunotherapy was 31.8% in short TKI-PFS group and 10% in long TKI-PFS group (p=0.04). Subgroup analysis of IO-PFS showed a high consistency with the overall study, as no matter with age < 65 years old, male, no smoker, ECOG PS0-1, EGFR 19DEL or L858R, treated with gefitinib or erlotinib, received immunotherapy in second line or third line and beyond, the results significantly favored patients with TKI-PFS < 10 months.

      figure1.jpg

      Conclusion

      The PFS of EGFR-TKIs is an independent predictive marker for subsequent IO combination treatment in EGFR mutated patients after resistant to EGFR-TKI. EGFR mutated NSCLC patients with short PFS to EGFR-TKIs conferred better response to following anti-PD-1/PD-L1 based immunotherapy. The underlying mechanism need to be further explored.

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    P77 - Immunotherapy (Phase II/III Trials) - Combining Different Immunotherapeutic Approaches (ID 254)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P77.03 - A Phase II Study of KN046 (Bispecific Anti-PD-L1/CTLA-4) in Patients (pts) with Metastatic Non-Small Cell Lung Cancer (NSCLC) (ID 1665)

      00:00 - 00:00  |  Presenting Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      KN046 is a novel bispecific antibody that blocks PD-L1 interaction with PD1 and CTLA-4 interaction with CD80/CD86. This multiple-cohort, single-arm phase II study evaluates preliminary safety and efficacy of KN046 in subjects with metastatic non-small cell lung cancer (NSCLC).

      Methods

      Eligible patients (pts) were advanced NSCLC without EGFR mutation or ALK fusions, progressed on 1st line platinum-based chemotherapy but not treated with any PD-(L)1 immune checkpoint inhibitor. All pts were given KN046 3 mg/kg (Cohort A) or 5 mg/kg (Cohort B) Q2W IV up to disease progression, intolerable toxicity, etc. Efficacy evaluation was performed by investigators per RECIST 1.1 every 8 weeks and safety and tolerability assessed per NCI-CTCAE v5.0.

      Results

      As of the July 27, 2020, 30 pts enrolled in Cohort A and 33 in Cohort B. Median age 59 years, male/female 51/12, PS 0/1 9/54, squamous NSCLC/Non-squamous NSCLC 23/40. ≥ Grade 3 treatment related treatment emergent adverse events (TRAEs) were seen in 21 (33.3%) pts, treatment related severe adverse events (SAE) 16 (25.4%) pts, immune related adverse events (irAEs) 34 (54.0%) pts, ≥ Grade 3 irAEs 11 (17.5%) pts. Common (≥ 10%) TRAEs were infusion related reaction (16, 25.4%), anemia (14, 22.2%), rash (13, 20.6%), hyperglycemia (12, 19.0%), abnormal hepatic function (10, 15.9%), hypothyroidism (10, 15.9%), alanine aminotransferase increased (8, 12.7%), asthenia (8, 12.7%), aspartate aminotransferase increased (7, 11.1%) and pruritus (7, 11.1%). Safety profile was comparable between two cohorts.

      As of cutoff date, 24 (37.5%) pts remained on the study treatment, and 39 (60.9%) pts discontinued treatment due to disease progression (n=27), AE (n=7), poor patient compliance (n=4) and one death. Median duration of drug exposure was 14 weeks (two to 56 weeks). ORR and DCR were 10.7% and 82.1%, 15.6% and 62.5% in cohort A and cohort B, respectively. Median PFS were 3.7 (2.9, 7.3), 3, 6 and 9-month PFS rate (95% CI) were 64.1% (49.4, 75.5), 36.6% (23.0, 50.4) and 34.2% (20.9, 47.9), 3, 6 and 9-month OS rate (95% CI) were 91.4% (80.5, 96.3), 86.9% (74.2, 93.6) and 81.0% (65.8, 89.9). In squamous NSCLC, median PFS was 7.3 (3.7, NE), 3, 6 and 9-month PFS rate (95% CI) was 80.0% (54.9, 92.0), 55.9% (27.0, 77.2) and 46.6% (19.0, 70.3), 3, 6 and 9-month OS rate (95% CI) were 100.0% (100.0,100.0), 88.2% (60.2, 96.9) and 88.2% (60.2, 96.9).

      Conclusion

      The bispecific antibody, KN046 was well tolerated and effective as 2nd line treatment of advanced NSCLC. KN046 showed promising PFS and OS benefit in squamous NSCLC.

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    P79 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Chemotherapy (ID 256)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P79.02 - Updated OS and Time to Second Progression with First-Line Camrelizumab Plus Chemo vs Chemo for Advanced Non-Squamous NSCLC (ID 1732)

      00:00 - 00:00  |  Presenting Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      At the pre-specified interim analysis of the CameL phase 3 study, camrelizumab plus chemo (carboplatin + pemetrexed) as first-line therapy significantly improved the PFS compared with chemo alone and showed acceptable safety profile in patients with advanced non-squamous NSCLC without sensitizing EGFR and ALK alterations (2019 WCLC OA04.03). Herein, we provide an update on OS and PFS2 (time to second progression) based on long-term follow-up.

      Methods

      Eligible patients were randomized 1:1 to receive 4 to 6 cycles of chemo with (n=205) or without (n=207) camrelizumab, followed by pemetrexed with or without camrelizumab as maintenance therapy. Crossover to camrelizumab monotherapy was permitted for patients in the chemo alone group who had radiological disease progression. Data on post-study anticancer therapy and outcomes were collected. PFS2 was defined as time from randomization to disease progression after the first disease progression event or death, whichever occurred first. There was no multiplicity adjustment, and nominal one-sided P values are presented. ClinicalTrials.gov number: NCT03134872.

      Results

      At data cutoff on February 25, 2020, the median follow-up duration was 19.3 months (IQR 9.8−23.7). 35 (17.1%) patients in the camrelizumab plus chemo group and 18 (8.7%) in the chemo alone group were still receiving the assigned first-line study treatment. Camrelizumab plus chemo prolonged median overall survival, as compared with chemo alone (27.9 months [95% CI 21.9−not reached] vs 20.5 months [95% CI 15.9−24.­­4]; HR 0.73 [95% CI 0.55−0.96]; P=0.0117). Second-line or later therapy was received by 98 (47.8%) patients in the camrelizumab plus chemo group and 135 (65.2%) patients in the chemo alone group. Median PFS2 was 18.9 months (95% CI 15.7−21.2) vs 12.5 months (95% CI 10.6−15.6) in patients who received vs did not receive first-line camrelizumab (HR 0.66 [95% CI 0.52−0.84]; P=0.0004). Benefits in OS and PFS2 with camrelizumab plus chemo were also found in patients with PD-L1 TPS ≥1% (Table). The safety profile was consistent with the previous report at interim analysis.

      Table.

      OS

      PFS2

      No. events/No. patients

      HR (95% CI)

      P value

      No. events/No. patients

      HR (95% CI)

      P value

      Camrelizumab plus chemo

      Chemo alone

      Camrelizumab plus chemo

      Chemo alone

      All patients (n=412)

      44.9%

      54.6%

      0.73 (0.55−0.96)

      0.0117

      60.0%

      71.5%

      0.66 (0.52−0.84)

      0.0004

      Patients with PD-L1 TPS ≥1% (n=255)

      38.4%

      49.6%

      0.70 (0.48−1.02)

      0.0318

      53.6%

      67.5%

      0.64 (0.46−0.88)

      0.0027

      Conclusion

      Camrelizumab plus carboplatin and pemetrexed as first-line therapy showed long-term benefit in OS and PFS2 compared with chemo alone in Chinese patients with advanced non-squamous NSCLC without EGFR and ALK alterations, despite 48.3% of patients in the chemo alone group receiving subsequent immunotherapy. No new safety signal was observed. This combination represents a potential standard first-line therapy for these patients.

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    P83 - Immunotherapy (Phase II/III Trials) - Immunotherapy Plus Targeted Therapy (ID 260)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 2
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P83.01 - Updated Survival and Biomarker Analysis of Camrelizumab and Apatinib in Previously Treated pts of Advanced Non-Squamous NSCLC (ID 1657)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Our previous report showed that camrelizumab combination with apatinib have showed promising results in previously chemotherapy-treated patients with advanced non-squamous NSCLC. We further report the updated survival data and biomarkers analysis here.

      Methods

      1.jpgWe conduct a multi-center single-arm phase 1b/II study investigating the safety and efficacy of camrelizumab and apatinib in previously treated patients with advanced NSCLC. This study included phase 1b apatinib dose escalation phase and phase II population expansion cohort. The primary endpoints were safety and ORR respectively. Patients of non-squamous NSCLC who received apatinib 250 mg orally once daily in combination with camrelizumab 200 mg intravenously on day 1 every 2 weeks were included into this analysis (NCT03083041). 22C3 array was used for PD-L1 immunohistochemistry and OseqTM-pan cancer panel (including 636 genes and 1.95Mb) was used for the genomic alternation testing.

      Results

      Between March 21, 2017 and October 11, 2018, 105 patients were enrolled, 91patients had PD-L1 expression testing and 46 had sufficient tissue for NGS. As the cutoff of Aug 15, 2019, one had a confirmed complete response, 28 had confirmed partial response, and 48 had stable disease, ORR was 30.9% (29/94, 95% CI, 21.7-41.2%) in the efficacy-evaluable population (n=94). Median progression-free survival was 5.7 months (95% CI, 4.5–8.8) and median overall survival was 19.2 months (95% CI, 11.2-24.5) in all patients. PD-L1 expression was positive in 25(27.4%) patients, median TMB is 9 mutations/Mb, while STK11 and KEAP1 mutation were found in 7 and 10 patients respectively. Patients with PD-L1 TPS>1% and high TMB could not predict higher ORR (36.0% vs 22.7%, P = 0.20; 29.2% vs 36.4%, p=0.564, respectively) or longer PFS (median 6.8 vs 5.1 months, P = 0.61; 7.8 vs 8.0 months, P = 0.98). Notably, patients with STK11/KEAP1 mutation had a numerically higher ORR (42.9% vs 28.1%, P =0.327), longer PFS (median 9.4 vs 5.3, P = 0. 592) and statistically significantly longer OS (median NR vs NR, P = 0. 047) than those of wild type. The most common treatment-related adverse events of grade 3 or higher were hypertension (18 [17.1%]), palmar-plantar erythrodysesthesia syndrome (14 [13.3%]), and increased gamma-glutamyltransferase (10 [9.5%]).

      Conclusion

      Combined camrelizumab and apatinib had promising antitumor activity and acceptable safety in previously treated patients with advanced non-squamous NSCLC, especially in these with STK11 or KEAP1 mutation, phase III trial is ongoing for further validation (NCT04203485).

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      P83.03 - Efficacy of Camrelizumab (SHR-1210) Plus Apatinib in Advanced NSCLC with EGFR Mutation (ID 1864)

      00:00 - 00:00  |  Author(s): Caicun Zhou

      • Abstract
      • Slides

      Introduction

      Treatment options are still limited for pts with advanced EGFR mutated NSCLC and resistant to EGFR-TKI. Here, we reported preliminary efficacy and safety of PD-1 camrelizumab (SHR-1210) plus apatinib in pts with EGFR mutation.

      Methods

      In this open-label, multi-center phase Ib/II study, pts aged 18-70 years, with EGFR mutation, and had disease progression on or after one line of platinum-based chemotherapy and at least one kind of EGFR-TKI were enrolled in dose escalation phase Ib and in dose expansion phase II. All pts received apatinib 250mg orally once daily plus camrelizumab 200mg every two weeks until disease progression or intolerable toxicity ( NCT03083041). Primary endpoint was objective response rate (ORR). Exploratory analyses of response and survival were conducted in pts classified by EGFR mutation types.

      Results

      Between Nov, 2017 and Jan, 2019, 40 NSCLC pts (3 in phase Ib and 37 in phase II) with EGFR mutation were enrolled. As the cutoff of December 15, 2019, the median follow-up was 10.8 months (range, 0.5-18.6). Four pts were still receiving treatment at the time of analysis. Among all 40 pts, 22 (55.0%) had EGFR 19 deletion (19del), 14 (35.0%) had L858R mutation, and 3 (7.5%) had EGFR 20 insertion (20ins). ORR was 20.0% (8/40, 95% CI, 9.1%-35.6%) and disease control rate (DCR) 62.5% (25/40, 95% CI, 45.8%-77.3%) in the whole population. Median duration of response was not reached (95% CI, 3.5-NR), median progression-free survival (mPFS) was 3.2 months (95% CI, 1.5-6.4m), and overall survival was not reached. Subgroup analysis showed that the ORR in pts with EGFR 20ins (n=3) or EGFR L858R(n=14) was higher than those with EGFR 19del (n=22) (33.3% vs. 21.4% vs. 13.6%, p=0.65). Similarly, longer mPFS was seen in pts with EGFR 20ins or L858R than in those with EGFR 19del (8.3m vs. 5.4m vs. 2.8m, p=0.94) . The most common treatment-related adverse events of grade 3 or higher were hypertension (7 [16.3%]), proteinuria (5 [11.6%]), palmar-plantar erythrodysesthesia syndrome (4 [9.3%]), and hypertriglyceridemia (3 [7.0%]).

      Table 1. Efficacy of camrelizumab and apatinib combination treatment in advanced NSCLC pts with EGFR mutation

      Pts

      ORR

      DCR

      mPFS (mos)

      mOS (mos)

      All pts

      40

      20.0%

      62.5%

      3.2

      NR

      EGFR 19del

      22

      13.6%

      59.1%

      2.8

      NR

      EGFR L858R

      14

      21.4%

      64.3%

      5.4

      NR

      EGFR 20ins

      3

      33.3%

      66.7%

      8.3

      NR

      Conclusion

      Camrelizumab plus apatinib showed a moderate benefit in pts with EGFR mutated NSCLC and showed better efficacy in pts with EGFR 20ins or L858R mutation sub-types, warrant further investigation.

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