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Edurne Arriola Aperribay



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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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      FP14.05 - 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): Edurne Arriola Aperribay

      • 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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    MA12 - Controversies Old and New (ID 230)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
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      MA12.03 - Prognostic Value of Clinical Staging According to TNM in SCLC Patients; A Real-World SEER Database Analysis. (ID 1096)

      16:45 - 17:45  |  Presenting Author(s): Edurne Arriola Aperribay

      • Abstract
      • Slides

      Introduction

      Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with a rapid tumor growth and spreading. Little improvement has been made in this disease in the last 3 decades until the introduction of immunotherapy combinations in first line extensive stage SCLC (ES-SCLC). Platinum-etoposide combinations in this setting have shown a median overall survival (mOS) of approximately 8-10 months (mo) according to randomized clinical trials and metanalysis. The VALG staging system is broadly used and tumors are commonly classified according to their anatomical extension in limited or extended. However, the IASLC recommends the tumor, node, metastasis (TNM) staging classification, based on surgical series. We compared survival outcomes in real-life SCLC patients according to TNM staging to evaluate its prognostic value in this disease

      Methods

      We conducted a retrospective analysis in real-life patients included in the SEER database and diagnosed with SCLC between 2010-2015. Median OS and long-term survival (LTS) were analyzed according to clinical staging to assess TNM prognostic value in SCLC. Patients were stratified into TNM stages following the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual.

      Results

      Among the 26 221 patients included in this analysis, 50.7% were men and 55.7% were 65 years old or over. Eighty-two percent of the patients were Caucasian. After implementing the TNM classification system, 749 (2.9%) patients were registered in stage I, 735 (2.8%) in stage II, 6163 (23.5%) in stage III and 18 574 (70.8%) stage IV. The mOS for stages IA, IB, II, III and IV was 24 (20.5-27.5), 21 (17.84-24.16), 12 (1.4-20.6), 11 (10.6-13.4) and 6 (5.83-6.17) mo respectively. For these stages, the survival rate at 6 mo, 1, 2 and 5 years is shown in Table 1.

      Table 1. Survival rate at 6 months, 1, 2 or 5 years
      Survival rate Stage IA Stage IB Stage II Stage IIA Stage IIB Stage III Stage IIIA Stage IIIB Stage IV
      6 months 85.4% 79.6% 52.6% 82.1% 74.3% 64.4% 75.6% 73.7% 47.7%
      1 year 70.5% 67.5% 47.4%

      68.4%

      58.6% 47.3% 53.4% 50.4% 21.6%
      2 years 49.7% 44.4% 31.6% 44.8% 32.3% 25.8% 29.6% 25.0% 5.9%
      5 years 28.1% 25.1% N.A: 19.0% 15.6% 11.3% 13.6% 11.0% 1.6%

      Conclusion

      This real world-data analysis in SCLC patients shows the prognostic value of TNM staging and that there has been no improvement in mOS and LTS in this disease over the last years. It also corroborates the IASLC recommendation and emphasizes the importance of performing clinical staging according to TNM since it may sub-classify more precisely the limited stage disease.

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    OA01 - Established Drugs in Special Populations and New Drugs in Established Populations (ID 226)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Immunotherapy (Phase II/III Trials)
    • Presentations: 1
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      OA01.07 - A Phase II Study of the Oral Selective AXL Inhibitor Bemcentinib with Pembrolizumab in Patients with Advanced NSCLC (ID 3647)

      09:15 - 10:15  |  Author(s): Edurne Arriola Aperribay

      • Abstract
      • Presentation
      • Slides

      Introduction

      AXL is a mediator of resistance to immunotherapy and a negative prognostic factor for NSCLC. Bemcentinib (BGB324), a first-in-class, oral, selective and potent AXL kinase inhibitor, enhances checkpoint inhibitor (CPI) efficacy in pre-clinical models through tumor-immune mechanisms. Increasingly, the combination of doublet chemotherapy with checkpoint inhibitors (Chemo-CPI) is a commonly used option for advanced NSCLC, and recurrence following such first line therapy represents an area of great unmet need. BGBC008 addresses the unmet need for NSCLC patients who fail 1L SOC.

      Methods

      BGBC008 is a PhII single-arm, 2-stage study with bemcentinib (200mg/d) and pembrolizumab (200 mg/q3wk) for previously-treated Stage IV lung adenocarcinoma comprising 3 cohorts: chemotherapy-failed IO-naïve patients (post-Chemo), patients progressing on prior CPI therapy (post-CPI monotherapy) and platinum-doublet chemotherapy in combination with pembrolizumab (post-Chemo-CPI). Primary endpoint was ORR according to RECIST1.1 with pre-defined criteria to proceed from the first to second stage in each cohort. Secondary endpoints included DCR, PFS, OS and safety. Exploratory endpoints include biomarker analysis and correlation with clinical endpoints, including composite (tumor and immune cell) cAXL score, PD-L1 TPS, and genome-wide mutational and transcriptome analyses.

      Results

      As of August 2020, enrollment in the post-Chemo cohort and stage 1 of the post-CPI monotherapy cohort is completed. Results of the post-Chemo cohort (n=50) and post-CPI monotherapy stage 1 cohort (n=16) were previously presented. Stage 2 of the post-CPI monotherapy cohort and stage 1 of the post-Chemo-CPI cohort are currently recruiting into the study.

      In patients treated to date, common TEAEs (>25% of patients) for NSCLC patients receiving the bemcentinib + pembrolizumab combination were: increased ALT (29%; 10% G3+), AST (29%; 5% G3+), and diarrhoea (29%; 1% G3+). All cases of treatment-related transaminase increase were reversible and managed with concomitant administration of steroids and treatment interruption.

      Having previously demonstrated a very high clinical benefit rate in post-Chemo and post-CPI monotherapy (stage 1) in cAXL-positive patients (73% and 85%, respectively), and low probability of clinical benefit in cAXL-negative patients (40% and 0%, respectively) further focus on the predictive value of cAXL in second line patients following either CPI monotherapy or Chemo-CPI relapse will be reported, together with transcriptional analysis to identify gene based predictive signatures.

      Conclusion

      Overall, bemcentinib in combination with pembrolizumab was well-tolerated and shows promising clinical activity in relapsed lung cancer. The key unmet need population of second line patients refractory to CPI monotherapy or Chemo-CPI will be presented together with translational data. Clinical Trial Registration: NCT03184571

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    P48 - Small Cell Lung Cancer/NET - Chemo - IO (ID 236)

    • 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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      P48.04 - IMfirst; Phase IIIB Safety Study of Atezolizumab Plus Chemotherapy in a Real World Population of Untreated ES-SCLC (ID 1929)

      00:00 - 00:00  |  Author(s): Edurne Arriola Aperribay

      • Abstract
      • Slides

      Introduction

      The standard of care for first line extensive stage small cell lung cancer (ES-SCLC) has been platinum-based chemotherapy (C) for more than 2 decades. Carboplatin (CP)/cisplatin (CPT) plus etoposide (ET) have shown a median overall survival (mOS) of approximately 8-10 months (mo) according to randomized clinical trials and metanalysis. Real-world data show a mOS of 6 mo in stage IV disease and a 5 year survival rate under 2%, highlighting the need for more effective therapies. IMpower133, combining atezolizumab (anti–PD-L1) with CP plus ET, was the first clinical trial to show significant improvement over standard C with a good safety profile. The addition of atezolizumab to C resulted in significantly longer mOS and median progression free survival (mPFS), with a mOS of 12,3 mo (10.8, 15.9) for atezolizumab plus CP and ET and 10,3 mo (9.3, 11.3) with C alone, HR: 0.70 (0.54, 0.91). Also, the 18-month landmark OS increased a 13% in the atezolizumab plus CP/ET (34%) arm compared with the placebo plus CP/ET (21%) arm. As a result, the combination of atezolizumab plus C is considered a category 1 preferred option according to NCCN and SEOM Spanish guidelines.

      Given the high-unmet need for new therapies for ES-SCLC, it is of considerable interest to evaluate the safety of atezolizumab in a broader spectrum of SCLC patients that mimics more closely a real world clinical practice population.

      Methods

      IMfirst (ML41599) is a phase IIIB, open label, single arm, multicenter study rolled out in Spain (30 sites) designed for patients with untreated ES-SCLC. The primary objective is to assess the safety of atezolizumab in combination with C (CP or CPT), according to investigator´s choice (IC), plus ET. This clinical trial includes a population of ES-SCLC patients that would have been screened out from some of the previous studies. ECOG performance status 2, asymptomatic untreated brain metastases, underlying stable autoimmune diseases or HIV+ patients are eligible. Induction phase includes 4 or 6 cycles (IC) of atezolizumab (1200 mg IV on day 1) plus C, with 21 day cycles. Maintenance therapy with atezolizumab every 3 weeks continues until evidence of persistent radiographic disease progression, loss of clinical benefit, symptomatic deterioration or unacceptable toxicity. The primary endpoint includes incidence, nature, and severity of adverse events. Key secondary endpoints are mPFS assessed by the investigator, mOS, objective response rate, duration of response and quality of life. Exploratory endpoints include comprehensive genomic profiling. Foundation Medicine panels will be performed in archival or freshly obtained tumor tissues if available, and it is mandatory for blood samples collected at baseline and progression. Currently the enrollment is ongoing and 10 patients have been included. IMfirst study recruitment will be open until 150 patients are enrolled. EudraCT Number: 2019-002784-10.

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