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Yun Fan



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    FP03 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) (ID 151)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP03.01 - Immune Microenvironment Features and Efficacy of PD-1/PD-L1 Blockade in Non-Small-Cell Lung Cancer Patients with EGFR or HER2 Exon 20 Insertions (ID 932)

      00:00 - 00:00  |  Presenting Author(s): Yun Fan

      • Abstract

      Introduction

      Insertions in exon 20 (Ex20ins) of EGFR and HER2 are relatively insensitive to first- and second-generation EGFR-tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC). This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with EGFR and HER2 Ex20ins.

      Methods

      Clinical characteristics, coexisting mutations, and outcomes to EGFR-TKIs and immune checkpoint blockade were reviewed for NSCLC patients with exon 20 mutations of EGFR or HER2. Data obtained included the molecular spectrum (extended genotyping for mutations in 324 cancer-related genes), as well as tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs).

      Results

      1.png1270 NSCLC patients were identified. Of these, 504 (39.7%) cases had EGFR mutations and 6.9% (35/504) of them had EGFR Ex20ins. Meanwhile, 21 (1.7%) cases with HER2 Ex20ins were detected. Comprehensive genomic profiling identified A767_V769dup variant (25.0%) was the most common type in tumors with EGFR Ex20ins. Co-occurring mutations were not uncommon including TP53 (45%), PIK3CA (20%), CDKN2A (10%), and EGFR amplification (20%). The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than for those with HER2 mutations (48.6% vs. 19.0%, P=0.027). High TMB and PD-L1 expression was independently associated with significantly poor prognosis (P=0.025, P=0.045; respectively) while there was no association between CD4+/CD8+ TILs and prognosis in EGFR or HER2 mutant NSCLC. Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins.4.png

      Conclusion

      NSCLC patients with EGFR/HER2 Ex20ins had similar genomic characteristics and distinct immune features when compared to common EGFR mutations. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the potential reason for the different responses to PD-1/PD-L1 blockage.

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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      FP14.12 - Quality of Life and Subgroup Analysis in a Phase 3 Randomized Study of Ensartinib vs Crizotinib in ALK–Positive NSCLC Patients: eXalt3. (ID 3852)

      00:00 - 00:00  |  Author(s): Yun Fan

      • Abstract

      Introduction

      Ensartinib (X-396) is a novel second-generation ALK tyrosine kinase inhibitor (TKI). In a phase 3 study interim analysis, ensartinib showed statistically significant improvement of median PFS over crizotinib in patients with ALK+ NSCLC who were ALK TKI naive or received up to one prior chemotherapy line, including higher efficacy against brain metastases. Ensartinib was well tolerated, with low grade rash, pruritus, edema, and transaminitis as the most frequent treatment-related AEs. Here we plan to present subgroups analyses and the quality of life outputs of the phase 3 eXalt3 study (NCT02767804).

      Methods

      Patients with locally tested ALK+ NSCLC (ITT population) were randomized 1:1 to ensartinib (225 mg QD orally) or crizotinib (250 mg BID orally). No crossover was allowed. Patients were stratified by prior chemotherapy, ECOG PS, brain metastases, and geographic region. The modified ITT (mITT) population was prespecified to include all centrally ALK+ patients by Abbott FISH test. The primary endpoint was blinded independent review committee (BIRC)–assessed progression-free survival (PFS; RECIST v.1.1). Secondary endpoints included overall survival (OS), overall response rate (ORR), and time to treatment failure (TTF) in the brain and patients reported outcomes (PRO). PRO data collection included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30). A linear mixed model for repeated measures was used to analyze change from baseline in the Global Health Status/Quality of Life subscale (GHS/QOL), with a change of greater than or equal to ten points deemed meaningful. Time to symptom deterioration will be presented.

      Results

      In total, 290 patients were randomized (ensartinib [n=143]; crizotinib [n=147]).Median age was 54.1 y, 26% of patients had prior chemotherapy, and 36% of patients had baseline CNS metastases (5% had prior brain radiotherapy). The mITT population included 247 patients (ensartinib [n=121]; crizotinib [n=126]). At the July 1, 2020, data cutoff, 139 BIRC-assessed PFS events (73%) occurred in the ITT population and 119 (63%) in the mITT population. Median PFS was 25.8 months with ensartinib vs 12.7 months with crizotinib (HR, 0.52; P=.0003 by log-rank test) with a median follow-up of 23.8 and 20.2 months in the ITT population. Median PFS was not reached with ensartinib vs 12.7 months with crizotinib in the mITT population (HR, 0.48; P=.0002 by log-rank test). New subgroup analyses in mITT for ensartinib showed a trend for higher efficacy by prior chemotherapy vs no chemotherapy (mPFS NR vs 25.8). Both global health status (GHS) as well as 5 functional and 9 symptom domains within EORTC QLQ-C30 had clinical meaningful improvement over time for ensartinib. Ensartinib delays the time to worsening of GHS with HR =0.83 (95% CI [0.57, 1.20]) vs crizotinib. Complete subgroup analyses (forest plot and multivariate analyisis) will be presented at the conference as well as OS updates. Comprehenive EORTC QLQ-C30 and Lung Cancer Symptom Scale scores will also be reported at the conference.

      Conclusion

      In ALK+ NSCLC patients ensartinib represents a new option in first-line setting. QOLs data support its favorable safety profile. Relevant subgroups analyses to evaluate its clinical impact will be presented at the meeting.

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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: 1
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      JICC01.14 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 4273)

      07:00 - 09:00  |  Author(s): Yun Fan

      • Abstract

      Introduction
      RET fusions have been reported as oncogenic drivers in 1% to 2% of non-small cell lung cancer (NSCLC) patients. Pralsetinib is a highly potent and selective RET kinase inhibitor targeting oncogenic RET alterations. A global phase I/II ARROW study (NCT03037385) has demonstrated broad and durable antitumor activity of pralsetinib in a variety of advanced RET-altered solid tumors. Here we present the efficacy and safety results from the phase II NSCLC extension group that enrolled patients from China sites. Methods
      RET fusion+ Chinese NSCLC patients previously treated with platinum-based chemotherapy were enrolled and dosed with pralsetinib 400 mg QD. The primary objectives were to assess the objective response rate (ORR) by blinded independent central review (BICR) per RECIST v1.1 and safety profile in Chinese patients. Results

      From Aug to Dec 2019, a total of 37 patients were enrolled; most (94.6%) of the patients had ECOG PS of 1 and about half (48.6%) had received ≥3 prior systemic regimens. As of the data cut-off (22 May 2020), 28 patients remained on study treatment and 9 discontinued from pralsetinib (4 due to disease progression and 3 due to adverse events). The median treatment duration was 6.1 (range: 0.9-9.4) months. In 32 evaluable patients who had measurable disease at baseline per BICR, the ORR was 56.3% (95% CI: 37.7, 73.6) (1 complete response [CR] and 17 partial responses [PR]); in addition, 2 patients achieved PR pending confirmation. Clinical benefit rate (defined as the rate of confirmed CR or PR, or stable disease lasting ≥ 16 weeks from the first dose) was 81.3% (95% CI: 63.6, 92.8). Disease control rate was 96.9% (95% CI: 83.8, 99.9), and tumor regression was observed in all 13 patients with stable disease. The median time to response was 1.9 (range: 1.7-5.5) months. Median duration of response (DOR) was not reached; 6-month DOR rate was 83.1% (95% CI: 61.5, 100). All 37 patients experienced at least one treatment emergent adverse event (TEAE). The most frequently reported TEAEs were aspartate aminotransferase increased (83.8%), neutrophil count decreased (70.3%), anaemia (67.6%), white blood cell count decreased (56.8%), and hypertension (51.4%). Grade ≥ 3 TEAEs occurred in 25 (67.6%) patients, with the most common being neutrophil count decreased (24.3%), anaemia (24.3%), hypertension (16.2%), hypophosphataemia (13.5%), platelet count decreased (10.8%) and hypokalaemia (10.8%). There were no pralsetinib related AEs leading to death.

      Conclusion

      This is the first pivotal study to show that pralsetinib has deep and durable antitumor activity, and is well-tolerated in a cohort of Chinese patients with RET fusion+ NSCLC previously treated with platinum-based chemotherapy. The data are consistent with previously reported data from the global population in the ARROW trial. Overall, pralsetinib demonstrated a favorable benefit-risk profile, potentially offering a transformative medicine to Chinese RET-fusion driven advanced NSCLC patients.

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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  |  Author(s): Yun Fan

      • 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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    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  |  Author(s): Yun Fan

      • Abstract

      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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    PS01 - Presidential Symposium (Japanese, Mandarin, Spanish Translation Available) (ID 143)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PS01.10 - Discussant (ID 4253)

      07:00 - 09:00  |  Presenting Author(s): Yun Fan

      • Abstract

      Abstract not provided

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    PS02 - Presidential Symposium (Re-Broadcast) (Japanese, Mandarin, Spanish Translation Available) (ID 275)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PS02.10 - Discussant (ID 4293)

      18:00 - 20:00  |  Presenting Author(s): Yun Fan

      • Abstract

      Abstract not provided