Virtual Library

Start Your Search

Jianying Zhou



Author of

  • +

    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
    • +

      EP1.14-52 - Variants Distribution and Clinical Outcomes to Crizotinib According to Molecular Features in ALK-Rearranged NSCLCs (ID 2027)

      08:00 - 18:00  |  Presenting Author(s): Jianying Zhou

      • Abstract
      • Slides

      Background

      ALK rearrangements are important oncogenic drivers in non-small-cell lung cancer (NSCLC). Crizotinib, an oral tyrosine kinase inhibitor targeting ALK, MET, and ROS1 tyrosine kinases, showed marked antitumor activity in patients with ALK-positive NSCLC. However, clinical responses to crizotinib among different ALK variants are found to be heterogeneous. This study explored the correlation of molecular characteristics and clinical outcomes to crizotinib in ALK-positive patients.

      Method

      33 patients with advanced NSCLC whose formalin-fixed paraffin-embedded tissue samples profiled using 168-cancer-related gene panel were identified with ALK rearrangements. Clinical/molecular characteristics and clinical outcomes to crizotinib of these patients were collected.

      Result

      Of the 33 ALK-rearranged patients, four cases harbored concurrent oncogenic driver mutations of the other 7 well-established lung cancer-related genes (EGFR, ERBB2, ROS1, RET, BRAF, KRAS and MET), including three MET amplifications and one KRAS G12V. The most frequently occurring ALK fusion partner was EML4, detected in all the 33 patients. Nine cases harbored more than one ALK rearrangement in the same sample. Among different variants of EML4-ALK, variant 1 (E13:A20; n=14, 43%) occurred most frequently, followed by variant 3 (E6:A20; n=10, 30%) and variant 2 (E20:A20; n=5, 15%). After crizotinib treatment (n=33), survival analysis revealed that patients with concomitant TP53 displayed inferior trend in terms of PFS (9.5 vs 15.0 months, p=0.07) and OS (not reached vs not reached, p=0.07) than TP53-negative patients. In addition, patients harboring variant 1 displayed favorable trend of PFS and OS than those with other variants (PFS, 22.0 vs 10.0 months, p=0.14; OS, not reached vs 26.0 months, p=0.09), even these differences were not significantly due to limited cohort size.

      Conclusion

      This study illustrated the distribution pattern of ALK fusions in Chinese NSCLCs, and demonstrated the differential clinical outcomes of ALK-rearranged patients according to specific molecular features. This study might improve basic knowledge of the heterogeneous responses of ALK-positive patients to crizotinib and provide guidance for clinicians to design appropriate treatment on ALK-positive NSCLCs.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA09 - EGFR & MET (ID 128)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • +

      MA09.09 - Long-Term Outcomes to Tepotinib Plus Gefitinib in Patients with <i>EGFR</i>-Mutant NSCLC and MET Dysregulation: 18‑Month Follow-Up (Now Available) (ID 1783)

      15:15 - 16:45  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      In EGFR-mutant NSCLC, MET amplification may cause resistance to EGFR tyrosine kinase inhibitors (TKIs). In a Phase Ib/II study in EGFR TKI-resistant patients with EGFR-mutant MET+ NSCLC, progression-free survival (PFS) and objective response rate (ORR) after ≥6 months of follow-up were improved with tepotinib (a highly selective MET TKI) plus gefitinib, compared with chemotherapy, particularly in patients with MET amplification. Here we present data at ≥18 months of follow-up.

      Method

      Asian patients with advanced, EGFR+, T790M-, MET+ NSCLC with resistance to prior EGFR TKIs were randomized to receive oral tepotinib 500 mg/day+gefitinib 250 mg/day or ≤6 cycles of cisplatin/carboplatin+pemetrexed chemotherapy±pemetrexed maintenance until confirmed progression, unacceptable toxicity, or withdrawal. Primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, overall survival (OS) and safety. Subgroup analyses were preplanned in MET IHC3+ and MET amplification populations (NCT01982955).

      Result

      Low recruitment halted full enrolment with 55 of 156 planned patients enrolled.

      As of 12-Dec-2018, median (range) duration of treatment with tepotinib+gefitinib was 21.4 (4.6, 110.9) weeks, with 3 patients still receiving treatment; and with pemetrexed was 18.0 (3.0, 60.4) weeks. 15 patients (62.5%) received ≥4 cisplatin/carboplatin cycles.

      Better outcomes were reported with tepotinib+gefitinib vs chemotherapy (Table), particularly in patients with MET IHC3+ (PFS: HR 0.35 [90% CI 0.17–0.74], OS: 0.32 [0.14–0.75]) or MET amplification (PFS: HR 0.13 [90% CI 0.04–0.43], OS: 0.08 [0.01–0.51]).

      Drug-related grade ≥3 adverse events (AEs) occurred in 17 (54.8%) patients receiving tepotinib+gefitinib and 12 (52.2%) patients receiving chemotherapy. Any-cause AEs leading to discontinuation occurred in 3 (9.7%) patients receiving tepotinib+gefitinib and 1 (4.3%) receiving chemotherapy. Dose reductions due to AEs were reported in 5 (16.1%) vs 4 (17.4%) patients.

      Conclusion

      Tepotinib+gefitinib has durable antitumor activity in patients with EGFR-mutant NSCLC with MET IHC3+ or MET amplification, and was generally well tolerated. MET amplification will be further explored as a biomarker for tepotinib.

      Table: Summary of efficacy data

      Population

      Tepotinib + gefitinib

      Chemotherapy

      HR/OR
      (90% CI)

      Overall MET+*

      Patients, n

      31

      24

      mPFS, months (90% CI)

      4.9 (3.9, 6.9)

      4.4 (4.2, 6.8)

      0.67 (0.35, 1.28)

      mOS, months (90% CI)

      17.3 (12.1, 37.3)

      18.7 (15.9, 20.7)

      0.67 (0.33, 1.37)

      ORR, n (%) [90% CI]

      14 (45.2) [29.7, 61.3]

      8 (33.3) [17.8, 52.1]

      1.99 (0.56, 6.87)

      MET IHC3+

      Patients, n

      19

      15

      mPFS, months (90% CI)

      8.3 (4.1, 21.2)

      4.4 (4.1, 6.8)

      0.35 (0.17, 0.74)

      mOS, months (90% CI)

      37.3 (24.2, 37.3)

      17.9 (12.0, 20.7)

      0.32 (0.14, 0.78)

      ORR, n (%) [90% CI]

      13 (68.4) [47.0, 85.3]

      5 (33.3) [14.2, 57.7]

      4.33 (1.03, 18.33)

      MET amplification

      Patients, n

      12

      7

      mPFS, months (90% CI)

      21.2 (8.3, NE)

      4.2 (1.4, 7.0)

      0.13 (0.04, 0.43)

      mOS, months (90% CI)

      37.3 (NE, NE)

      13.1 (3.3, NE)

      0.08 (0.01, 0.51)

      ORR, n (%) [90% CI]

      8 (66.7) [39.1, 87.7]

      3 (42.9) [12.9, 77.5]

      2.67 (0.37, 19.56)

      CEP-7, centromere protein 7; CI, confidence interval; EGFR, epidermal growth factor receptor; GCN, gene copy number; HR, hazard ratio; IHC, immunohistochemistry; IRC, independent review committee; ITT, intention to treat; MET, mesenchymal-epithelial transition factor; NE, not estimable; OR, odds ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival

      All efficacy outcomes are investigator-assessed by RECIST v1.1.

      *IHC2+/IHC3+/gene amplification.

      MET amplification is defined as GCN ≥5 and/or MET/CEP-7 ratio ≥2. 17 of 19 patients with MET amplification have MET overexpression (IHC3+).

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA11 - Immunotherapy in Special Populations and Predictive Markers (ID 135)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Immuno-oncology
    • Presentations: 2
    • Now Available
    • +

      MA11.02 - KEYNOTE-042 China Study: First-Line Pembrolizumab vs Chemotherapy in Chinese Patients with Advanced NSCLC with PD-L1 TPS ≥1% (Now Available) (ID 1772)

      14:00 - 15:30  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      In the global, open-label KEYNOTE-042 study (NCT02220894), pembrolizumab significantly improved OS vs chemotherapy in PD-L1–positive locally advanced/metastatic NSCLC without targetable EGFR/ALK aberrations (HRs: TPS ≥50%, 0.69; ≥20%, 0.77; and ≥1%, 0.81). We present the very first results for Chinese patients enrolled in the KEYNOTE-042 global and China extension (NCT03850444) studies.

      Method

      The global and extension studies were designed identically. Patients were randomized 1:1 (stratified by ECOG PS 0/1, squamous/nonsquamous histology, and TPS ≥50%/1‒49%) to up to 35 cycles of pembrolizumab 200 mg Q3W or up to 6 cycles of paclitaxel/pemetrexed + carboplatin with optional pemetrexed maintenance (nonsquamous only). Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20%, and ≥1%. No alpha was allocated to the China extension analysis. Overall, ~350 patients from China will be enrolled including 140 patients with TPS ≥50%, to determine the OS effect of pembrolizumab and consistency across outcomes in Chinese patients.

      Result

      As of September 4, 2018, 262 Chinese patients with PD-L1–positive (TPS ≥1%) NSCLC were enrolled (global, n=92; China extension, n=170) and randomized to pembrolizumab (n=128) or chemotherapy (n=134). 146 patients (55.7%) had PD-L1 TPS ≥50%; 204 (77.9%) had PD-L1 TPS ≥20%. After median (range) follow-up of 11.3 (0.1‒23.2) months, 32 patients (25.0%) were still receiving pembrolizumab and 6 (4.8%) were receiving pemetrexed maintenance. Pembrolizumab improved OS vs chemotherapy in patients with PD-L1 TPS ≥50%, ≥20%, and ≥1% (Table). Among patients who received ≥1 dose of pembrolizumab (n=128) or chemotherapy (n=125), grade 3–5 drug-related AEs occurred in 17% vs 68%, respectively.

      Overall Survival

      n

      Median (95% CI), mo

      HR (95% CI)

      PD-L1 TPS ≥50%

      Pembrolizumab

      72

      20.0 (15.5–NR)

      0.62 (0.38–1.00)

      Chemotherapy

      74

      14.0 (10.0–17.9)

      PD-L1 TPS ≥20%

      Pembrolizumab

      101

      20.0 (17.4–NR)

      0.62 (0.41–0.95)

      Chemotherapy

      103

      13.7 (10.1–17.9)

      PD-L1 TPS ≥1%

      Pembrolizumab

      128

      20.0 (17.4–NR)

      0.65 (0.45–0.94)

      Chemotherapy

      134

      13.7 (10.1–17.9)

      PD-L1 TPS 1–49%a

      Pembrolizumab

      56

      19.9 (11.9–NR)

      0.69 (0.40–1.20)

      Chemotherapy

      60

      10.7 (8.3–20.9)

      NR, not reached. aExploratory analysis.

      Conclusion

      Pembrolizumab monotherapy improved OS with a favorable safety profile vs platinum-based chemotherapy as first-line therapy in Chinese patients with locally advanced/metastatic NSCLC without sensitizing EGFR/ALK aberrations and a PD-L1 TPS ≥1%. Findings are consistent with the global study primary endpoints, supporting first-line use of pembrolizumab for PD-L1–expressing advanced/metastatic NSCLC in China.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      MA11.06 - A PII Study of Toripalimab, a PD-1 mAb, in Combination with Chemotherapy in EGFR+ Advanced NSCLC Patients Failed to Prior EGFR TKI Therapies (Now Available) (ID 1160)

      14:00 - 15:30  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      EGFR TKI is the standard 1st line therapy for the patients (pts) with advanced NSCLC harboring EGFR mutations. While PD-1 checkpoint blockade has become an integral component of disease management for EGFR wild type NSCLC pts at various settings, platinum-based chemotherapy is still the standard of care for EGFR mutated NSCLC pts who progress after EGFR targeting therapy. Early attempts to combine EGFR TKI with checkpoint blockade had resulted in exacerbated immune related toxicity in the lung. Here we aimed to prospectively evaluate toripalimab, a humanized PD-1 mAb approved for 2nd line treatment of melanoma, in combination with chemotherapy to treat EGFR mutated NSCLC pts after failure of EGFR targeting therapy.

      Method

      This is a phase II, multicenter, open-label, single-arm study for pts with EGFR activating mutations who have failed prior EGFR-TKI therapies without T790M mutation or failed osimertinib treatment. Pts were treated with 240mg or 360mg fixed dose toripalimab once every 3 weeks in combination with carboplatin and pemetrexed for up to 6 cycles, followed by toripalimab plus pemetrexed maintenance therapy until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) at week 12 as assessed by investigator per RECIST v1.1 once every 6 weeks. Secondary endpoints were safety, ORR, DOR, DCR, TTR, PFS, OS, PK and immunogenicity.

      Result

      f14_2_1_3_pub.png

      Forty pts were enrolled from Apr 25, 2018 to March 22, 2019 with 52.5% female pts and a median age of 57.5. 57.5% pts harbored EGFR exon19 deletion while 42.5% pts had exon21 L858R mutation. Only 1 pt had T790M mutation who progressed after osimertinib treatment. In ITT population, 13 confirmed partial response (PR) and 22 stable disease (SD) were observed at week 12 for a 32.5% ORR. As of Jul 25 2019, among 40 pts, 20 confirmed PR and 15 SD were observed for a 50% ORR (95% CI, 33.8% to 66.2%) and an 87.5% DCR (95% CI, 73.2% to 95.8%). Median progression free survival (PFS) was 7.0 months, and median duration of response (DOR) was 7.0 months. Treatment emergent adverse events (TEAE) occurred in 39 (97.5%) of the pts, grade 3 or higher events occurred in 25 (62.5%) of pts including two deaths. Most common AE included leukopenia, neutropenia, thrombocytopenia, anemia, nausea, and loss of appetite. Treatment discontinuation due to AE occurred in 4 (10%) of the pts.

      Conclusion

      Anti-PD-1 mAb, toripalimab in combination with carboplatin and pemetrexed has shown a promising anti-tumor efficacy with a tolerable safety profile for advanced NSCLC patients with EGFR mutated who progressed after EGFR TKI therapies. Pts will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). A phase III registration study will be initiated in May 2019.

      (Clinical trial information: NCT03513666)

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MA14 - The Adequate MTarget Is Still the Issue (ID 140)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
    • +

      MA14.05 - A Randomized Phase III Trial of Fruquintinib Versus Placebo in Patients with Advanced Non-Small Cell Lung Cancer (FALUCA) (Now Available) (ID 1490)

      15:45 - 17:15  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      Fruquintinib, an orally active kinase inhibitor that selectively targets vascular endothelial growth factor (VEGF) receptor, demonstrated significant benefit in progression-free survival and disease control in a randomized Phase II study in patients with non-small-cell lung cancer (NSCLC) who had failed two lines of chemotherapy. This Phase III FALUCA trial is a randomized, double-blind, placebo-controlled, multicenter trial designed to confirm the efficacy in the same patient population (NCT02691299).

      Method

      From December 2015 to February 2018, 45 clinical centers across China participated in the trial. A total of 730 patients aged 18-75 with advanced NSCLC who had failed two lines of chemotherapy were screened and 527 who met the eligibility criteria were enrolled into the study. Patients were stratified based on epidermal growth factor receptor mutation status and prior use of VEGF inhibitor therapy, and were randomized in a 2:1 ratio to receive fruquintinib (n=354) or placebo (n=173) once daily in a 3 weeks on/1 week off 4-week cycle. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response. The final data cutoff was on September 21, 2018.

      Result

      Median OS was 8.94 months for fruquintinib and 10.38 months for placebo (hazard ratio, 1.02; 95% CI, 0.816 to 1.283; p=0.841). Median PFS was 3.68 months for fruquintinib comparing to 0.99 months for placebo, respectively (hazard ratio, 0.34; 95%CI, 0.279 to 0.425; p<0.001). The ORR and DCR were 13.8% and 66.7% for fruquintinib, compared with 0.6% and 24.9% for placebo (both p<0.001), respectively. The most frequent treatment-emergent adverse events with fruquintinib (≥grade 3) were hypertension (20.7%), hand-foot syndrome (11.0%), and proteinuria (1.4%). A sensitivity analysis revealed that median OS was significantly prolonged with fruquintinib compared with placebo in patients who received no subsequent systemic anti-tumor therapies (7.00 months versus 5.06 months ; hazard ratio, 0.64; 95%CI, 0.453 to 0.903; p=0.010).

      Conclusion

      The FALUCA trial failed to meet the primary end point of OS while confirming significant benefit in secondary end points including PFS, ORR and DCR. The safety profile of fruquintinib in this patient population was acceptable and consistent with that identified in the Phase II study. A post-hoc sensitivity analysis revealed that the anti-tumor therapies that patients received post disease progression probably contributed to the failure of this study on the primary end point.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • +

      OA02.03 - The Third Generation EGFR Inhibitor (EGFR-TKI) HS-10296 in Advanced NSCLC Patients with Resistance to First Generation EGFR-TKI (Now Available) (ID 766)

      10:30 - 12:00  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      HS-10296 is an oral, potent, high selective third generation EGFR tyrosine-kinase inhibitor (EGFR-TKI) for sensitizing mutations, and the EGFR Thr790Met (T790M) resistance mutation which has been demonstrated by phase I study. This phase II, open-label, multicenter single-arm study was designed to confirm the efficacy and safety of HS-10296 in a large population of non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, who had progressed after first generation EGFR-TKI treatment.

      Method

      Patients aged at least 18 years with centrally confirmed EGFR T790M-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC after first generation EGFR-TKI treatment received HS-10296 110 mg orally once daily until disease progression, or intolerable toxicity, or patient withdrawal. Patients with asymptomatic, stable brain metastases not requiring steroids were allowed to enroll. The primary endpoint was the objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1 every 6 weeks. Response endpoints (ORR and disease control rate [DCR]) were assessed in response analysis set. Secondary end points including progression-free survival (PFS), duration of response (DoR), depth of response (DepOR), overall survival (OS) and safety were evaluated in full analysis set. The final data cutoff was on Jan 5, 2019. The study is still ongoing.

      Result

      Totally, 244 patients (median age 60.8) entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients) between May 16, 2018 to Oct 23, 2018. 2 patients were excluded from the evaluable for response analysis set (n=242) due to absence of measurable disease at baseline by independent central review. At data cutoff, 182 (74.6%) patients remained on treatment. The median duration of follow-up was 4.7 months. 160 of 242 patients achieved confirmed partial responses by independent central review. The ORR was 66.1% (95% CI: 59.8-72.1). The DCR was 93.4% (95% CI: 89.5-96.2). The most common adverse reactions (≥ 10%) were blood creatine phosphokinase increased (43 [17.6%]), aspartate aminotransferase increased (29 [11.9%]), pruritus (28 [11.5%]), rash (28 [11.5%]) and alanine aminotransferase increased (26 [10.7%]). The most common all-causality grade 3 and 4 adverse events were blood creatine phosphokinase increased (14 [5.7%]) and hyponatraemia (4 [1.6%]). Serious adverse events were reported in 30 (12.3%) patients, of which 19 (7.8%) were investigator assessed as possibly treatment-related to HS-10296. Three deaths were due to adverse events; one was related to cardiopulmonary failure, other two events occurred after disease progression. There was no interstitial lung disease during study treatment.

      Conclusion

      HS-10296 has demonstrated good clinical benefit with minimal toxicity in patients with EGFR T790M-positive NSCLC patients who have progressed after first generation EGFR-TKI treatment. The Phase III study has already launched comparing HS-10296 with gefinitib in advanced NSCLC patients with EGFR sensitizing mutations. (The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    OA04 - Immuno Combinations and the Role of TMB (ID 126)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • +

      OA04.03 - A Randomized Phase 3 Study of Camrelizumab plus Chemotherapy as 1<sup>st</sup> Line Therapy for Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer (Now Available) (ID 1682)

      15:15 - 16:45  |  Author(s): Jianying Zhou

      • Abstract
      • Presentation
      • Slides

      Background

      Platinum-based chemotherapy remains 1st line therapy for advanced non-small cell lung cancer (NSCLC) without oncogenic drivers in China. Camrelizumab (SHR-1210, a potent anti‒PD-1 monoclonal antibody) has shown promising activity in multiple malignancies. Here, we report interim analysis results on efficacy and safety of camrelizumab plus carboplatin/pemetrexed as 1st line treatment in Chinese advanced/metastatic non-squamous NSCLC patients with negative oncogenic drivers.

      Method

      In this open-label, randomized, multicenter phase 3 study (SHR-1210-303), patients with advanced/metastatic, non-squamous NSCLC with negative EGFR or ALK were stratified by sex and smoking history (≥ 400/year versus ˂ 400/year) and were randomly assigned (1:1) to receive 4 to 6 cycles of carboplatin (AUC=5) plus pemetrexed (500 mg/m2) with or without camrelizumab (200 mg), followed by pemetrexed with or without camrelizumab as maintenance therapy up to disease progression or intolerable toxicity. Treatment was given every 3 weeks. Crossover to camrelizumab monotherapy was permitted for patients in the chemotherapy arm who had confirmed disease progression. The primary endpoint was PFS per blinded independent central review according to RECIST v1.1. Secondary endpoints included ORR, DCR, DoR and OS. Data of subgroup analysis will be reported. Clinical Trials.gov number: NCT03134872.

      Result

      Between May 12, 2017 and Jun 6, 2018, 419 patients were randomized, among whom 205 received camrelizumab plus chemotherapy and 207 received chemotherapy treatment. After a median follow-up of 11.9 months, median PFS was 11.3 months (95% CI 9.5‒not reached) in camrelizumab plus chemotherapy arm and 8.3 months (95% CI 6.0‒9.7) in chemotherapy arm (HR 0.61 [95% CI 0.46‒0.80], p=0.0002). ORR, DCR, DoR and OS with camrelizumab plus chemotherapy were superior to chemotherapy (Table 1). Grade 3/4 adverse events occurred in 66.8% of patients in camrelizumab plus chemotherapy arm and 51.2% of patients in chemotherapy arm. There were 5 treatment-related deaths in camrelizumab plus chemotherapy arm and 4 in chemotherapy arm.

      Table 1. Responses per blinded independent central review and overall survival in the total study population

      Camrelizumab plus chemotherapy

      (n=205)

      Chemotherapy alone

      (n=207)
      p-value
      Objective response rate 60.0% (53.0‒66.8) 39.1% (32.4‒46.1) p<0.0001
      Disease control rate 87.3% (82.0‒91.6) 74.4% (67.9‒80.2) p=0.0009
      Duration of response (months) 17.6 (11.6‒NR) 9.9 (8.5‒13.8) p=0.0356
      Overall survival (months) NR (17.1‒NR) 20.9 (14.2‒NR) p=0.0272
      Data are shown in % (95% CI) or median (95% CI). NR: not reached.

      Conclusion

      First-line camrelizumab plus chemotherapy shows substantial clinical benefit in patients with advanced/metastatic non-squamous NSCLC with negative EGFR or ALK in terms of PFS, ORR, and OS and acceptable safety profiles. The combination should become novel standard 1st line therapy for this population.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.01 - Advanced NSCLC (ID 158)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.01-106 - Clinical Features and Tumor Immune Microenvironment Related to Acquired Resistance to EGFR-TKI in NSCLC Patients with EGFR Mutation (ID 2343)

      09:45 - 18:00  |  Author(s): Jianying Zhou

      • Abstract

      Background

      First generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) provide significant clinical benefit in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutation. However, patients with initial response to EGFR-TKI ultimately develop acquired resistance to EGFR-TKI treatment, which approximately 50% resistant patients develop second EGFR T790M mutation. New treatment strategy for NSCLC patients harboring EGFR T790M mutation has been available. For those EGFR T790M negative patients, chemotherapy is currently the standard treatment. However, the efficacy of immunotherapy in EGFR T790M mutation NSCLC patients is unknown. Our study focused on the relationship between the clinical features and EGFR T790M mutation status, and the tumor immune microenvironment change before and after acquired resistance to EGFR-TKI in NSCLC patients with EGFR mutation.

      Method

      In this study, we retrospectively evaluated 89 patients with EGFR mutation who received first generation EGFR-TKIs treatment at the First Affiliated Hospital of Zhejiang University between February 2012 and July 2018. All patients were performed second biopsy after acquired resistance to EGFR-TKI. EGFR T790M mutation, epithelial-mesenchymal transition (EMT) and tumor-infiltrating CD4 and CD8 lymphocytes (TILs) in 13 patients with paired biopsy specimens before and after resistance to EGFR-TKI were measured by next generation sequencing (NGS) and immunohistochemistry analyses respectively.

      Result

      Among the 89 eligible patients, EGFR T790M mutation rate was 59.6% (53/89). EGFR T790M mutation was not related with age, gender, smoking status, tumor stage, performance status, but related to the initial EGFR mutation type (EGFR exon 19 deletion or exon 21 L858R mutation). Patients with EGFR exon 19 deletion had significantly higher T790M mutation rate than that with exon 21 L858R mutation (p=0.025). Interestingly, among 11 patients with family cancer history, 10 patients acquired T790M mutation. Furthermore, patients with T790M mutation had longer progression-free survival (PFS) compared to T790M-negative patients (75.5% vs 63.9%, P<0.05). In the small cohort of 13 patients, 6 patients developed EMT after acquired resistance. TILs according to the CD4+ and CD8+ lymphocyte density were not significantly changed in all 13 patients before and after acquired resistance.

      Conclusion

      Our findings indicate that patients with EGFR exon 19 deletion、longer PFS or family cancer history may have higher possibility to develop second EGFR T790M mutation after resistance to EGFR-TKI treatment. The incidence of EMT was higher than we expected, providing further research and clinical treatment ideas. There is no change in TILs after resistance to EGFR-TKI in patients with or without EGFR T790M mutation, but this need further study due to the limited samples in this study.

    • +

      P1.01-36 - Clinical Potential of Tissue Tumor Mutational Burden (tTMB) and Blood TMB (bTMB) as a Biomarker in Non-Small Cell Lung Cancer (ID 2045)

      09:45 - 18:00  |  Presenting Author(s): Jianying Zhou

      • Abstract
      • Slides

      Background

      Higher tissue TMB (tTMB) or blood TMB (bTMB) levels are associated with better response of immunotherapy in patients with non-small cell lung cancer (NSCLC). The clinical utility of bTMB and tTMB for clinical indications remain to be determined.

      Method

      Comprehensive genomic profiling were performed on 28 paired tissue and plasma samples using 520-gene panel, which has been validated to accurately reflect the actual tTMB and bTMB using in-house validation. The max allelic fraction (max.AF) of 5% in tissue and 0.5% in plasma were defined as the detection limit for TMB assessment, and samples with max.AF < 5% (n=1) in tissue and 0.5% in plasma (n=6) were excluded. Union-TMB represents the union of tTMB and bTMB, and union-TMB-class-10 denotes union-TMB of 10 is used as the cutoff for grouping.

      Result

      Correlation analysis revealed that bTMB and tTMB diaplayed significant consistency with each other (R2=0.953). Next, associations of clinical characteristics and TMB status were analyzed. Older patients were significantly associated with higher tTMB (p=0.009) than younger ones, but slightly correlated with TMB-max (p=0.055) and TMB-union (p=0.079). We also found that male patients more commonly had higher tTMB (p=0.001), bTMB (p=0.011), max-TMB (p<0.001), union-TMB (p<0.001) and union-TMB-class-10 (p=0.018) than female ones with statistical significance, while smokers usually had higher tTMB (p=0.003), max-TMB (p=0.011), union-TMB (p=0.004) and union-TMB-class-10 (p=0.044) than non-smokers. Next, the correlation between TMB and clinical response were investigated in 19 patients who received nivolumab treatment. We found patients who had partial response to nivolumab commonly had higher bTMB than those experienced stable disease or progression (p=0.076); patients with bTMB>=10 or bTMB>=16 achieved higher objective response rate (ORR) than that with bTMB<10 (42.9% vs 0.0%) or bTMB<16 (66.7% vs 10.0%); patients with squamous cell carcinoma achieved significantly favorable progression-free survival than those with adenocarcinoma (p=0.019).

      Conclusion

      We revealed that tTMB and bTMB were strongly correlated with each other for TMB assessment. Higher tTMB was strongly correlated with smokers and males compared with non-smokers and females. Higher bTMB predicted better response and ORR to nivolumab, indicating that bTMB could function as a biomarker for prognosis prediction. Prospective studies are necessary to investigate the clinical implications of tTMB and bTMB in a larger cohort of patients.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.04 - Immuno-oncology (ID 164)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
    • +

      P1.04-37 - Dioscin Elicits Anti-Tumor Immunity by Inhibiting Macrophages M2 Polarization via JNK and STAT3 Pathways in Lung Cancer (ID 3100)

      09:45 - 18:00  |  Author(s): Jianying Zhou

      • Abstract

      Background

      Tumor associated macrophage (TAM) is an important component in tumor microenvironment. Generally, TAM exhibits the function of M2-like macrophage, which is closely related to angiogenesis and tumor progression. Dioscin, a natural steroidal saponin, has shown its powerful anti-tumor activity recently. However, the mechanism of dioscin involved in immune-regulation is still obscure. Our study aimed to find the potentional anti-tumor role of dioscin in macrophages polarization regulation in lung cancer.

      Method

      Flow cytometry was used to analyze the percentage of M1 macrophages(CD86+F4/80+ or NOS2+F4/80+) and M2 macrophages(CD209+F4/80+ or CD206+F4/80+) with dioscin treatment in vivo and in vitro. Real-time quantitative PCR was used to detect the expression of Arg-1, CD206 and NOS2, IL-6 mRNA. The level of IL10 and IL-12 secreted by macrophages was also analyzed using flow cytometry. Phagocytosis was determined by the amount of fluorescence-labeled latex beads internalized by BMDMs with microscopy and Flow cytometry. JAK-STAT and MAPK signaling pathways were detected by Western-Blot method.

      Result

      We observed dioscin induced macrophages M2-to-M1 phenotype transition in vitro and inhibited IL-10 secretion. Meanwhile, the phagocytosis of macrophages was enhanced. In subcutaneous lung tumor models, dioscin inhibited the augmentation of M2 macrophage populations. Furthermore, dioscin down-regulated STAT3 and JNK signaling pathways in macrophages in vitro. Additionally, condition mediums from dioscin-pretreated macrophages inhibited the migration of 3LL cells and the tube-formation capacity of HUVEC cells.

      Conclusion

      Dioscin may act as a new anti-tumor agent by inhibiting TAMs via JNK and STAT3 pathways in lung cancer.