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Qing Zhou



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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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      FP14.17 - Efficacy and Safety of Pralsetinib in Chinese Patients with Advanced RET Fusion+ Non-Small Cell Lung Cancer after Platinum-Based Chemotherapy (ID 2954)

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

      • Abstract
      • Slides

      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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    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  |  Presenting Author(s): Qing Zhou

      • 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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    P72 - Tumor Biology and Systems Biology - Basic and Translational Science - Tumor Microenvironment (ID 211)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Tumor Biology and Systems Biology - Basic and Translational Science
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P72.02 - Cellular Landscape of Tumor Immune Microenvironment and Genetic Signatures Identify Prognostic of LUAD (ID 736)

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

      • Abstract
      • Slides

      Introduction

      Tumour microenvironment (TME) has been recognized to support the initiation and progression of lung adenocarcinoma (LUAD). The innate and adaptive immune cells in the lung TME harbour both tumour-promoting and tumour-suppressing activities, which may also predict clinical outcome. Therefore we carried out a systematic analysis of cellular interactions in tumor immune microenvironment. And identify cell-intrinsic and cell-extrinsic pathways cell types and activation states that may serve as biomarkers of overall survival (OS).

      Methods

      Public gene-expression data and relevant clinical annotation were obtained from Gene-Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Three TME infiltration patterns were comprehensively analyzed in 442 LUAD patients using CIBERSORT algorithm and the LM22 gene signature. Based on the TME patterns, we build a model to calculate TMEscore based on gene set variation analysis via ssGSEA algorithm. Functional enrichment analysis were performed by GO and KEGG.

      Results

      Four datasets with available outcome data and clinical information in GEO and TCGA-LUAD were enrolled in our study. GSE72094 was used as the training cohort, while GSE11969, GSE26939, GSE31210 and TCGA-LUAD was used as validation cohorts. TME cell network established based on GSE72094 depicted a comprehensive landscape of tumor-immune cell interactions, cell lineages, and their correlation with OS (Fig. 1A, 1B). Three subgroups with distinct TME signature gene sets were obtained/identified based on unsupervised hierarchical clustering in 442 LUAD cases. OS in TME gene subgroup B was significantly longer than which in TME gene subgroup A and subgroup C. TME gene group B was associated immune activation (Fig. 1C). TMEscore was further constructed using principal component analysis algorithms. Lower TMEscore is significantly associated with better prognosis. Functional annotation analysis showed TMEscore had a positive correlation with cell cycle, DNA replication, homologous recombination, mismatch repair, nucleotide excision repair and DNA damage repair (Fig. 1D). The enriched pathways in subtype with lowest/low TMEscore involved bile_acid_metabolism, fatty_acid_metabolism and myogenesis. While high TMEscore subtype was characterized by significant enrichment of interferon_alpha_response, myc_targets and unfolded_protein_response pathway (Fig. 1E). TMEscore model was then validated on 525 patients from GEO datasets and 585 patients from TCGA-LUAD project and proved to be a valuable method for prognostic stratification of LUAD except for TNM stage(Fig. 1F).

      fig-1.png

      Conclusion

      Variability in the composition of the tumor immune microenvironment contributes to heterogeneity in OS. Deeper validation is in need to define the positive association between lower TMEscore and longer OS.

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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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      P76.60 - FLAIR: Phase II Study of Osimertinib plus Bevacizumab versus Osimertinib in Advanced NSCLC Patients with EGFR L858R Mutation (ID 3221)

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

      • Abstract
      • Slides

      Introduction

      The 3rd generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib monotherapy has been considered as the new standard of care for advanced EGFR mutated non-small-cell lung cancer (NSCLC) patients. However patients with L858R mutation have achieved lower efficacy of EGFR-TKIs than those with 19Del mutation, even with osimertinib. Herein to improve the efficacy of L858R population is still unmet medical needs. While CTONG1509 study has presented the addition of bevacizumab to 1st generation EGFR TKI erlotinib appears to significantly improve L858R patients’ progression free survival the combination of osimertinib and bevacizumab is worth deep exploration.

      Here we present the rationale and study design for the FLAIR trial, a multicenter, open label, randomized, phase II study.

      Methods

      Study entry will be limited to adults aged ≥ 18 years with primary recurrent or metastatic nonsquamous non-small-cell lung cancer with documented an EGFR exon 21 L858R mutation. Patients will be randomized 1:1 to receive osimertinib 80 mg once daily plus bevacizumab 15mg/kg every 3 weeks or osimertinib monotherapy 80 mg once daily until disease progression or unacceptable toxicity.

      The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of overall response (DoR), time to treatment failure (TTF), overall survival rate at 2 years, and safety and tolerability.

      In the HR assumption of 0.65, sample size of 90 patients is driven by the needs of 67% statistic power for the test at the significance level of 0.2, two sided, with the accrual period of 8 months and the longest follow-up of 32 months.

      The first analysis (primary analysis) data cut-off (DCO) point will be happened when 70% data maturity for PFS based on investigator assessment (according to RECIST 1.1) has been reached (depending on the actual event rate).

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      P76.78 - Evaluation of the Development of Brain Metastases in Patients Treated with Dacomitinib or Gefitinib from ARCHER 1050 Study (ID 3461)

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

      • Abstract
      • Slides

      Introduction

      Dacomitinib (Vizimpro®) is a competitive, irreversible, small-molecule inhibitor of epidermal growth factor receptor (EGFR). ARCHER 1050 is a multicenter, Phase 3 study conducted in patients with metastatic or recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R substitution mutations) with no prior therapy for metastatic disease. Dacomitinib significantly improved progression-free survival (PFS) and overall survival (OS) against gefitinib with hazard ratios of 0.59 (p<0.001) and 0.75 (p=0.0155), respectively. The present analysis evaluated the risk factors of development of brain metastases from ARCHER 1050, including treatment, baseline characteristics, and dacomitinib exposure.

      Methods

      CNS imaging was performed in ARCHER 1050 at baseline for all patients and on treatment for patients with clinically suspected brain metastases at the discretion of investigators. Brain lesion data were recorded based on investigator (INV) and independent radiologic central (IRC) reviews. Patients, excluding any history or evidence of brain or leptomeningeal metastases as per the protocol exclusion criteria, were randomized to receive dacomitinib (starting dose of 45 mg QD with allowance of dose reduction to 30 mg or 15 mg) or gefitinib (250 mg QD). Dacomitinib exposure was measured by population PK model-based trough concentrations, average concentrations, or AUC at the end of Cycle 1. Other baseline characteristics were evaluated for its potential association with on treatment development of brain metastases using logistic regression (glm() function).

      Results

      Based on INV review, no patients in the dacomitinib arm (n=227) presented with baseline brain metastases and 1 patient presented with baseline brain metastases in the gefitinib arm (n=225). After median follow up of 22.1 months, total of 4 (1.8%) patients developed brain metastases in the dacomitinib arm comparing to 14 (6.2%) in the gefitinib arm [odds ratio (OR): 0.27 (95% CI: 0.08, 0.77; p=0.0229)]. Of the 4 patients with developed brain metastases in the dacomitinib arm, 1 patient had no dose reduction and the other 3 patients had dose reduced to 30 mg QD. Similarly, by IRC review, no patients presented with brain metastases at baseline in dacomitinib arm while 4 patients in gefitinib arm were retrospectively found to have baseline brain metastases. According to IRC, only 1 (0.4%) patient in dacomitinib arm and 9 (4.0%) patients in gefitinib arm developed new brain lesions [OR: 0.11 (95% CI: 0.01, 0.57; p=0.0341)]. No other covariates (eg., smoking status, race, sex, baseline ECOG performance status, EGFR mutation type, and baseline brain metastases) were associated with development of new brain lesions. Dacomitinib exposure was explored as a covariate for the INV reported new brain lesions and was not found to be associated with development of brain metastases.

      Conclusion

      Dacomitinib is associated with a lower incidence of symptomatic CNS progression in the ARCHER 1050 study.

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    P85 - Targeted Therapy - Clinically Focused - MET (ID 262)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P85.02 - NGS could not Replace FISH Regarding to MET Amplification as an Optimal Biomarker (ID 1581)

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

      • Abstract
      • Slides

      Introduction

      MET amplification (MET amp) is known as an important mechanism of resistance to EGFR-TKIs in NSCLC. We investigated the association between survival benefits and MET status identified by different methods, to explore the appropriate biomarker to select patient for MET-TKIs treatment in advanced NSCLC.

      Methods

      Method: FISH (fluorescence in situ hybridization), IHC (immunohistochemistry) and NGS (next generation sequences) were performed prospectively from FFPE/liquid samples with NSCLC. MET amplification by FISH was defined as MET/CEP7 ratio>2 or CN(copy number )>6 and served as the standard reference for over-express by IHC and copy number gain (CNG) by NGS. Objective response (OR) and PFS were used to confirm optimal biomarker for MET inhibitor.

      Results

      We identified MET dysregulation of 37 NSCLC patients by FISH, IHC and NGS before MET-TKIs administration and assessing the survival benefits of 33 cases treated MET inhibitor. The consistence of FISH, IHC and NGS was only 54%. They are the different population. MET amplification identified by FISH proved the best predictive efficiency for survival benefits. The PR rate was 82% (18/22) and median PFS was 4.8 months in MET amp, compared to 1.0 months for cases with non-MET amp (P= 0.004). Both MET dysregulations identified by NGS or IHC failed to distinguish the significant survival difference in patients with MET-TKIs. Comparing with MET amplification by FISH, effective cases were more seen in patients with CNG > 4.0 or IHC score >290 . Based on these two cut-off values:CNG > 4.0 or IHC score >290 still did not predict efficacy of MET inhibitors, suggesting CNG by NGS had no significant associations with efficacy benefits.

      Conclusion

      Compared to MET amplification identified by FISH, CNG dysregulation by NGS or MET protein over-express by IHC could not serves as the predictive biomarker for MET inhibitors.

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    PL03 - Bench to Bedside (Immunology) (Japanese, Mandarin, Spanish Translation Available) (ID 142)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PL03.07 - Monitoring Disease Through Genomic/Immune Markers (ID 3915)

      18:00 - 20:00  |  Presenting Author(s): Qing Zhou

      • Abstract

      Abstract not provided