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Koichi Goto



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    FP14 - Targeted Therapy - Clinically Focused (ID 252)

    • Event: WCLC 2020
    • Type: Posters (Featured)
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 2
    • 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  |  Presenting Author(s): Koichi Goto

      • 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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      FP14.10 - Efficacy and Safety of Selpercatinib (LOXO-292) in East Asian Patients with RET Fusion-Positive NSCLC (ID 1896)

      00:00 - 00:00  |  Author(s): Koichi Goto

      • Abstract
      • Slides

      Introduction

      Selpercatinib is a highly selective and potent, CNS-active, oral RET kinase inhibitor. Here we report the efficacy and safety analyses for the East Asian subgroup with RET fusion-positive NSCLC included in the Primary Analyses Set (PAS). Per regulatory authority agreement, the PAS was defined as the first 105 consecutively enrolled patients that had been previously treated with platinum-based chemotherapy.

      Methods

      Patients with RET fusion-positive NSCLC were enrolled to the global multicenter Phase 1/2 LIBRETTO-001 trial (NCT03157128), conducted in 89 sites across 16 countries, including 23 sites in 7 countries that enrolled patients who self-identified as Asian [Japan (12 patients), South Korea (11 patients), Singapore (5 patients), Hong Kong (5 patients), United States (5 patients), Australia (1 patient), and France (1 patient)]. Following the dose escalation Phase 1 portion, patients received the recommended Phase 2 dose of selpercatinib (160 mg orally, BID, 28-day cycles). The primary endpoint was independently-assessed objective response rate (ORR) per RECIST 1.1. Secondary endpoints included duration of response (DoR) and safety. The analyses reported herein examine the East Asian PAS patient subgroup using data from the 16-Dec-2019 cutoff date.

      Results

      A total of 40 East Asian patients included in the PAS were analyzed. Baseline demographics were: 60% female; median age 56 years (range: 35–80); 95% of patients with an ECOG performance status of 0 or 1. RET fusion partners included: KIF5B-RET (57.5%), CCDC6-RET (15.0%), NCOA4-RET (2.5%), other/unknown (25%). All patients received prior systemic therapy, including platinum-based chemotherapy (100% of patients), a multi-kinase inhibitor (52.5%), and anti-PD-1/PD-L1 therapy (57.5%). The median number of prior therapies was 3.0 (range 1–15). Independently-assessed ORR was 60.0% (95% CI=43.3–75.1, n=24/40). Median DoR was not reached at a median follow-up of 12 months. In the safety analysis of all East Asian patients with NSCLC dosed with selpercatinib (N=136), treatment-related adverse events (TRAEs) that occurred in ≥15% of patients were increased ALT/AST, dry mouth, hypertension, diarrhea, increased creatinine, QT prolongation, thrombocytopenia, peripheral edema, and rash. Only 1.5% (2 of 136) of East Asian patients discontinued selpercatinib due to TRAEs.

      Conclusion

      In this heavily pretreated population of East Asian patients with RET fusion-positive NSCLC, treatment with selpercatinib resulted in a marked and durable tumor response with a well-tolerated safety profile that was consistent with previously reported results from LIBRETTO-001. No new safety signals were identified.

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    IS04 - Industry Symposium Sponsored by Lilly Oncology: Implementing Precision Oncology in the Clinic: Diagnostic Challenges and Best Practices (ID 281)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 3
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      IS04.01 - Chair’s Welcome (ID 4320)

      13:00 - 14:00  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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      IS04.02 - Introduction to the Topic - A Brief Overview of the 15-Year Journey of Biomarker Driven Management of NSCLC (ID 4321)

      13:00 - 14:00  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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      IS04.07 - Symposium Close (ID 4326)

      13:00 - 14:00  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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    IS11 - Industry Symposium Sponsored by Amgen Oncology: Advancing the Next Frontier of Innovation in Lung Cancer Therapies (ID 288)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS11.03 - Current Unmet Need in KRAS G12C-Mutated NSCLC (ID 4357)

      13:00 - 14:00  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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    IS15 - Industry Symposium Sponsored by Amoy: Lung Cancer Biomarker Panel Testing (ID 292)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS15.03 - Biomarker Panel Testing: PCR Panel vs NGS Panel (ID 4372)

      13:00 - 14:00  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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    MA11 - Expanding Targetable Genetic Alterations in NSCLC (ID 251)

    • Event: WCLC 2020
    • Type: Mini Oral
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
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      MA11.02 - Chair (ID 4244)

      14:15 - 15:15  |  Presenting Author(s): Koichi Goto

      • Abstract

      Abstract not provided

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    OA04 - New Data from Rare EGFR Alterations (ID 223)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
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      OA04.04 - Amivantamab in Post-platinum EGFR Exon 20 Insertion Mutant Non-small Cell Lung Cancer (ID 3031)

      11:45 - 12:45  |  Author(s): Koichi Goto

      • Abstract

      Introduction

      Despite sharing similar tumor biology to other epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) tumors, no targeted therapies have been approved for NSCLC harboring EGFR Exon 20 insertion mutations (Exon20ins). The standard of care remains platinum-based chemotherapy for the front-line, with no clear subsequent options available. Amivantamab (JNJ-61186372) is a novel, fully human EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications, and has received FDA Breakthrough Therapy Designation for the treatment of patients with EGFR Exon20ins NSCLC after platinum-based chemotherapy. Here we present updated results on the Exon20ins cohort from the CHRYSALIS study (NCT02609776).

      Methods

      The dose escalation phase enrolled patients with advanced NSCLC to determine the recommended phase 2 dose (RP2D) of 1050 mg (1400 mg for ≥80 kg) amivantamab. The dose expansion phase assessed the safety and efficacy of amivantamab in patients with EGFR- and MET-mutant NSCLC treated at the RP2D. Disease response was assessed by the investigator per RECIST v1.1 and is presented for those patients with Exon20ins NSCLC who had progressed on prior platinum-based chemotherapy, were treated at the RP2D, and had at least 3 post-baseline disease assessments (18 weeks) or discontinued, progressed, or died prior to the 3rd assessment (the Post-Platinum Cohort). The data cutoff date was 8 Jun 2020.

      Results

      In the Post-Platinum Cohort (n=81), median age was 62 (42 – 84), 59% were women, 49% were Asian, median prior lines of therapy was 2 (1 – 7), and 53% were never-smokers. At a median follow-up of 6.5 months (1.1 – 29.3), investigator-assessed overall response rate (ORR) was 36% (29/81; 95% CI, 25 – 47), with all responders achieving partial response (PR). The clinical benefit rate (≥PR or stable disease ≥11 weeks) was 73% (59/81; 95% CI, 62 – 82). Responses were durable at a median of 6.8 months (95% CI, 5.0 – not reached) with ongoing responses in 18/29 (longest at 16+ months). Median progression-free survival was 8.3 months (95% CI, 5.5 – 12.7) and median overall survival was 22.8 months (95% CI, 14.0 – not reached).

      Among all phase 1 patients, across a variety of EGFR genomic alterations and lines of therapy, treated with amivantamab monotherapy at the RP2D (n=258), the most common adverse events (AEs) were rash (78%), infusion related reaction (IRR; 65%), and paronychia (40%). Additional EGFR-related AEs were stomatitis (19%), pruritus (19%), and diarrhea (11%). Grade ≥3 AEs were reported in 39% of patients; 14% were considered treatment-related, with rash (3%) and IRR (2%) being most frequent. No treatment-related deaths were reported. The incidence of treatment-related AEs leading to dose reduction and discontinuation was 10% and 3%, respectively.

      Conclusion

      Amivantamab treatment led to promising efficacy with durable responses in patients with EGFR Exon20ins NSCLC post-platinum doublet and continues to demonstrate a manageable safety profile in over 250 patients treated at the RP2D. A phase 3 study, PAPILLON, evaluating amivantamab in combination with chemotherapy in the front-line setting is in planning stages.

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    P15 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Novel Immunotherapeutics (Phase I) (ID 154)

    • Event: WCLC 2020
    • Type: Posters
    • 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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      P15.03 - A Phase 1/1b Study of Lazertinib as Monotherapy and in Combination with Amivantamab in Advanced EGFR-Mutated NSCLC (ID 1405)

      00:00 - 00:00  |  Presenting Author(s): Koichi Goto

      • Abstract
      • Slides

      Introduction

      The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has improved clinical outcomes for patients with EGFR-mutated non-small cell lung cancer (NSCLC); however, patients will inevitably progress due to acquired resistance mutations. Lazertinib is an oral, highly potent, mutant-selective, and irreversible EGFR TKI targeting both T790M and activating EGFR mutations while sparing wild type EGFR. Lazertinib has demonstrated efficacy against EGFR-mutated NSCLC in both systemic and central nervous system lesions due to its ability to cross the blood-brain barrier. Amivantamab (JNJ-61186372) is an EGFR-MET bispecific antibody with immune cell-directing activity that targets activating and resistance EGFR mutations and MET mutations and amplifications. The synergistic mechanisms of action of amivantamab, which targets the extracellular ligand binding domain, combined with lazertinib, which targets the intracellular active site, have the potential to more potently inhibit the EGFR pathway than either agent alone.

      Methods

      This is a phase 1/1b open-label, multicenter study in patients with advanced EGFR-mutated NSCLC (NCT04077463). The study was initially opened in 3 sites in Japan. Phase 1 dose escalation cohorts enrolled Japanese patients with metastatic or unresectable EGFR-mutated NSCLC who had progressed after available targeted therapies. Phase 1b combination cohorts assessed the safety and tolerability of lazertinib and amivantamab in increasing doses in Japanese patients. The phase 1b expansion cohort A will enroll patients who have progressed on prior treatment with both osimertinib and platinum-doublet chemotherapy, for treatment with the combination of lazertinib and amivantamab. The objective of phase 1 dose escalation cohorts is to confirm the recommended phase 2 dose (RP2D) and to evaluate the safety, tolerability, and pharmacokinetics of lazertinib as monotherapy (phase 1 dose escalation cohorts) and in combination with amivantamab (phase 1b combination cohorts) in Japanese patients. Phase 1b dose expansion cohort A is enrolling patients globally to further characterize the safety, tolerability, and preliminary antitumor activity of the combination of lazertinib with amivantamab at the global recommended phase 2 combination dose of 240 mg lazertinib orally daily and 1050 mg (1400 mg for patients ≥80 kg) amivantamab intravenously weekly for the first 28-day cycle and biweekly thereafter. The primary endpoints are frequency of dose limiting toxicity, overall response rate, duration of response, and clinical benefit rate based on investigator-assessed efficacy according to RECIST 1.1 criteria. Key secondary endpoints include adverse events as graded by NCI CTCAE criteria v4.03, pharmacokinetic parameters of lazertinib and amivantamab, progression-free survival, and overall survival.

      Results

      Fourteen Japanese patients have been enrolled in phase 1 dose escalation (n=11) and phase 1b combination (n=3) cohorts. No dose limiting toxicity has been observed, and the safety and tolerability of lazertinib monotherapy at the RP2D was confirmed in Japanese patients. Enrollment into phase 1b expansion cohort A is ongoing.

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    P75 - Immunotherapy (Phase II/III Trials) - Misc. Topics (ID 248)

    • 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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      P75.01 - Activity of Brigatinib in Alectinib-Resistant ALK-Positive NSCLC According to ALK Plasma Mutation Status From J-ALTA Trial (ID 3615)

      00:00 - 00:00  |  Author(s): Koichi Goto

      • Abstract
      • Slides

      Introduction

      Brigatinib is a selective and potent ALK tyrosine kinase inhibitor (TKI) with preclinical activity against wild-type ALK and a broad spectrum of ALK secondary mutants, known to confer clinical resistance to crizotinib, ceritinib, and alectinib. Brigatinib has shown promising efficacy in Japanese patients with ALK+ NSCLC previously treated with alectinib in a phase 2 trial (J-ALTA). As an exploratory correlative analysis, we examined the relationship of ALK mutation status with brigatinib treatment outcome by NGS analysis of cell free DNA (cfDNA) using plasma specimens at baseline prior to brigatinib treatment (baseline [BL]) in ALK+ NSCLC patients who progressed on alectinib or other ALK TKIs and enrolled in this study.

      Methods

      Plasma samples were analyzed using the PGDx elioTM plasma resolve (Personal Genome Diagnostics, Baltimore, MD, USA) to determine ALK kinase domain mutations and EML4-ALK fusion status. Brigatinib activity was defined by the confirmed objective response rate (ORR) (RECIST v1.1). Data are reported as of January 22, 2019 for J-ALTA trial.

      Results

      Of the 72 ALK+ NSCLC patients enrolled, evaluable plasma samples were obtained from 70 patients at BL; alectinib was the most recent ALK TKI (with or without prior crizotinib) in 51 patients. Of these, 30.0% (21/70) of patients had confirmed response to brigatinib, and 35.3% (18/51) of post-alectinib patients responded to brigatinib. Secondary ALK mutations were detected in plasma in 15.7% (11/70) of patients (10 post-alectinib and 1 post-ceritinib). ORR was confirmed in 45.5% (5/11) of these patients. Best responses in patients with secondary ALK mutations were: 5 confirmed partial responses (PRs); 4 stable disease (SD); 2 progressive disease (PD), including 1 confirmed PR and 2 SD in patients with ALK G1202R mutation at BL. No secondary ALK mutations were detected in 84.2% (59/70), ORR was confirmed in 27.1% (16/59) of these. Gene amplification was detected in only 1 patient (MYC gene amplification).

      BL EML4-ALK fusion was detected in 51.4% (36/70) of the post-ALK TKIs patients; 25.0% (9/36) of these had secondary ALK mutations. Post-BL samples were also collected from 49 patients at the end of brigatinib treatment. Secondary ALK mutations were detected in 7 patients: 1 with F1174L (also had G1202R at BL); 1 with E1210K (also had I1171S at BL); 5 with G1202R (2 not present at BL; 2 present at BL; 1 present at BL and S1206F also detected). MYC gene amplification was detected in 2 patients.

      Conclusion

      ALK fusions were detected in the plasma of over 50% of ALK+ NSCLC patients resistant to alectinib and/or other TKIs. Brigatinib demonstrated meaningful activity in ALK TKI-resistant patients regardless of the presence of secondary ALK mutations and EML4-ALK fusion status in plasma. Clinical trial information: NCT03410108.

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