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Jianhua Chang



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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): Jianhua Chang

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

    • Event: WCLC 2020
    • Type: Posters
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P47.01 - Plasma Exosomal Long RNA in SCLC Diagnosis and Prognosis (ID 1080)

      00:00 - 00:00  |  Author(s): Jianhua Chang

      • Abstract
      • Slides

      Introduction

      Little research has focused on blood exosomal transcription profile in small cell lung cancer (SCLC). The aim of this study is to identify plasma exosomal specific transcriptional profile in SCLC and explore the application value of plasma exosomal long RNA (exLR) in SCLC diagnosis and prognosis.

      Methods

      This study included 81 healthy people and 40 SCLC patients receiving standard first-line chemotherapy with etoposide and carboplatin/cisplatin. The efficacy was evaluated by progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). 19 Patients who achieved complete response (CR) or partial response (PR) as best response during the first-line therapy and had not progressed within the following 90 days after the end of first-line therapy were defined as chemosensitive. 21 Patients who achieved stable disease (SD) as best response or received progressive disease during the first-line therapy or within the following 90 days after the end of first-line therapy were defined as chemoresistant. Baseline plasma samples were collected from 40 SCLC patients (17 patients’ samples after 2 courses were collected) and 81 healthy people. Plasma exosomes were isolated and purified; exosomal RNA were extracted for high-throughout sequencing analysis.

      Results

      We obtained plasma exLRs profiles in SCLC and healthy control group. Bioinformatics analysis found that exLRs were significantly different between the SCLC and the healthy control group; between the chemosensitive and the chemoresistant group; between the baseline samples and the paired samples after 2 courses (Fig A-C). The differently expressed genes were enriched in tumor-related signal pathways.

      For 40 SCLC patients receiving first-line chemotherapy, ORR was 65.0%, DCR was 90.0% and mPFS was 6.0 months (95% CI, 4.3-7.7 months)(Fig D). Multivariate analysis showed that baseline brain metastases and baseline bone metastases were independent predictors of poor PFS (Fig E-F); 223 genes were independent predictors of PFS.

      There were 10 genes (AC107954.1, H2AFZP2, CALB2, IFITM9P, GFPT2, PLA1A, CHST10, AC021231.2, SETP20, HILPDA) intersected in differentially expressed genes between the SCLC and the healthy control group, differentially expressed genes between the chemosensitive and the chemoresistant group and independent predictors of PFS (Fig G). These 10 genes were highly expressed in both the SCLC group and the chemoresistant group (Fig H-I), and their high expression were independent risk factors for poor PFS.

      fig  .jpg

      Conclusion

      This study firstly identified the plasma exLRs profiles in SCLC patients, verified the feasibility and value of identifying biomarkers based on exLRs profiles in SCLC diagnosis and prognosis.

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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): Jianhua Chang

      • 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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