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Masahiro Tsuboi



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    IS02 - Industry Symposium Sponsored by AstraZeneca: Evolving the Role of Immunotherapy in Lung Cancer: ES-SCLC and Unresectable Stage III NSCLC (ID 278)

    • Event: WCLC 2020
    • Type: Industry Symposium
    • Track:
    • Presentations: 1
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      IS02.01 - Opening Remarks (ID 4309)

      10:30 - 11:30  |  Presenting Author(s): Masahiro Tsuboi

      • Abstract

      Abstract not provided

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    OA06 - Updates on EGFR Targeted Perioperative Therapy and Precision Adjuvant Chemotherapy (ID 118)

    • Event: WCLC 2020
    • Type: Oral
    • Track: Early Stage/Localized Disease
    • Presentations: 2
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      OA06.03 - Patient-Reported Outcomes from ADAURA: Osimertinib as Adjuvant Therapy in Patients with Resected EGFR Mutated (EGFRm) NSCLC (ID 3505)

      16:45 - 17:45  |  Author(s): Masahiro Tsuboi

      • Abstract

      The abstract for this presentation is currently under embargo or has not been submitted.

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      OA06.04 - Postoperative Chemotherapy Use and Outcomes from ADAURA: Osimertinib as Adjuvant Therapy for Resected EGFR Mutated NSCLC (ID 3464)

      16:45 - 17:45  |  Author(s): Masahiro Tsuboi

      • Abstract

      The abstract for this presentation is currently under embargo or has not been submitted.

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    P03 - Early Stage/Localized Disease - Clinical Trials in Progress (ID 112)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Early Stage/Localized Disease
    • Presentations: 3
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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      P03.02 - Neoadjuvant Osimertinib with/without Chemotherapy vs Chemotherapy for EGFR Mutated Resectable NSCLC: NeoADAURA  (ID 3386)

      00:00 - 00:00  |  Presenting Author(s): Masahiro Tsuboi

      • Abstract

      Introduction

      Background

      Approximately 30% of patients with NSCLC present with resectable disease. Primary treatment for resectable NSCLC is curative surgery; patient prognosis following surgery alone remains poor. Neoadjuvant chemotherapy is recommended in resectable stage-III NSCLC, regardless of EGFR mutation status, and has demonstrated clinical benefit. However, improved treatment options for stage II/III are needed. Recent studies indicate that EGFR-TKI therapy could potentially achieve tumour size reduction and clearance of micrometastases in the neoadjuvant setting; treatment effect can be assessed in resected specimens. Osimertinib is a third-generation, CNS-active EGFR-TKI, with superior efficacy to comparator EGFR-TKI in treatment-naïve EGFR mutation-positive (EGFRm) advanced NSCLC. In the Phase III ADAURA study (NCT02511106), osimertinib showed statistically significant DFS improvement (hazard ratio: 0.20 [99.12% confidence interval 0.14, 0.30; p<0.001) in resected stage IBꟷIIIA EGFRm NSCLC following adjuvant chemotherapy, when indicated. A recent study (NCT03433469) found neoadjuvant osimertinib was well tolerated in patients with Stage IꟷIIIA NSCLC. Efficacy and tolerability of osimertinib in advanced and adjuvant settings support its investigation as neoadjuvant treatment in resectable disease. NeoADAURA (NCT04351555) is a Phase III, controlled, randomised study assessing efficacy and safety of osimertinib (with/without chemotherapy) versus chemotherapy plus placebo as neoadjuvant treatment in resectable stage IIꟷIIIB EGFRm NSCLC.

      Methods

      Trial Design

      Eligible patients: ≥18 years (≥20 years, Japan), ECOG PS 0/1, primary non-squamous stage IIꟷIIIB (IASLC Cancer Staging Manual v8) NSCLC and confirmed EGFRm (Ex19del/L858R), deemed completely resectable. Prior treatment with systemic anti-cancer therapy for NSCLC is not allowed. Approximately 351 patients will be randomised 1:1:1 (Figure) to receive platinum-based chemotherapy (pemetrexed 500 mg/m2 plus carboplatin AUC5 or cisplatin 75 mg/m2) plus placebo (Arm 1; double-blind), platinum-based chemotherapy plus osimertinib 80 mg once-daily (Arm 2; double-blind) or osimertinib 80 mg once-daily alone (Arm 3; open-label). Patients will be stratified by disease stage (II/III), race (non-Asian/Chinese/other Asian) and EGFR mutation (Ex19del/L858R).

      Following three cycles of chemotherapy (Arms 1 and 2) or nine weeks of osimertinib (Arm 3), patients will undergo complete surgical resection of primary NSCLC. Treatment with osimertinib or placebo may continue until surgery, unless unacceptable toxicity/withdrawn consent/other discontinuation criterion. Post-surgery, patients will receive optimal care (investigator-defined); this may include adjuvant osimertinib treatment for three years (maximum)/until disease recurrence or unmanageable toxicity.

      The primary endpoint is MPR, (≤10% residual cancer cells in surgical specimen post-surgery) centrally assessed. Secondary endpoints include pCR, EFS, downstaging, DFS, OS and safety. MPR and EFS will be tested using hierarchal testing procedure at MPR primary analysis.

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      P03.03 - MERMAID-1: A Phase III Study of Adjuvant Durvalumab plus Chemotherapy in Resected NSCLC Patients with MRD+ Post-Surgery (ID 3322)

      00:00 - 00:00  |  Author(s): Masahiro Tsuboi

      • Abstract

      Introduction

      30% of non-small-cell lung cancer (NSCLC) patients present with surgically resectable disease at diagnosis. To reduce disease recurrence, adjuvant chemotherapy is standard of care (SoC) for patients with completely (R0) resected stage II/III NSCLC. However, 5-year disease-free survival (DFS) rates remain low (~40%), with a 5-year absolute benefit of only 5.4% derived from chemotherapy (Pignon et al. JCO 2008;26:3552-9). Determining who will benefit from adjuvant chemotherapy remains challenging. Identifying minimal residual disease (MRD) through detection of circulating tumour (ct) DNA post-surgery could predict early disease recurrence. Durvalumab is a selective, high‑affinity, human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. In the phase III PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression following radical platinum-based concurrent chemoradiotherapy, durvalumab improved progression-free survival (PFS) and overall survival (OS), demonstrating its efficacy in situations of residual disease. Further, initial data from POSEIDON showed durvalumab plus chemotherapy prolongs PFS versus chemotherapy in first line treatment of metastatic NSCLC. In the adjuvant setting (i.e. following complete tumour resection), this regimen could provide additional DFS benefit versus chemotherapy alone. MRD assessment could facilitate earlier, more selective adjuvant therapy for MRD+ patients, allowing for treatment intensification for this potentially biologically distinct disease, while minimising overtreatment of MRD– patients. MERMAID‑1 will investigate the efficacy and safety of adjuvant durvalumab + SoC chemotherapy versus placebo + SoC chemotherapy in patients with completely resected stage II/III NSCLC, to assess the benefits of adjuvant therapy in patients with MRD+ status.

      Methods

      MERMAID-1 (NCT04385368) is a phase III, parallel-arm, placebo-controlled, double‑blind, multicentre study, conducted across 16 countries. Patients aged ≥18 years with histologically confirmed EGFR-/ALK- Wild-type, stage II/III NSCLC will enter the first screening period; a personalised MRD panel will be created. Before randomisation, and following assessment of MRD status post-surgery, patients will be further screened for full eligibility (no evidence of disease recurrence, WHO/ECOG performance status 0/1). Patients who have received prior adjuvant therapy or durvalumab, and those with mixed small cell and NSCLC histology or evidence of post-operative disease recurrence are ineligible. MRD status will be determined via ctDNA analysis of plasma samples, collected 3–4 weeks post-surgery, and based on personalised panels (comprised of ≤50 tumour-specific DNA variants) created by whole exome sequencing analysis of the patient’s resected tumour tissue. Approximately 332 patients will be randomised 1:1 (stratified by disease stage, MRD status, and PD-L1 expression) to durvalumab (1500 mg, intravenously) or placebo, plus concurrent SoC chemotherapy, once every three weeks (Q3W) for 12 weeks. Patients will continue with durvalumab monotherapy/placebo Q4W thereafter, until Week 48 or disease recurrence, whichever occurs first. Following a baseline radiological scan prior to randomisation, patients will be assessed Q12W until disease recurrence (per RECIST v1.1). The primary endpoint is DFS in the MRD+ analysis set (investigator-assessed). Secondary endpoints include DFS in the full analysis set (FAS; investigator-assessed); DFS in the MRD+ analysis set and FAS (blinded independent central review); OS in the MRD+ analysis set and FAS; and safety and tolerability, and patient-reported outcomes.

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      P03.05 - CANOPY-N: Neoadjuvant Canakinumab and Pembrolizumab in Patients With Surgically Resectable Non-Small Cell Lung Cancer (ID 2981)

      00:00 - 00:00  |  Author(s): Masahiro Tsuboi

      • Abstract

      Introduction

      Complete surgical resection is the standard treatment for patients with stage I-IIIA non-small cell lung cancer (NSCLC). 5-year survival rates range from 19-50%, with most patients dying from distant recurrence. Neoadjuvant or adjuvant chemotherapy improves overall survival by only 5% in patients with NSCLC, and new treatment options are needed. Preliminary data with PD-1 or PD-L1 inhibitors as neoadjuvant therapy has shown major pathologic responses (MPR) or pathologic complete responses (pCR) in patients with early stage NSCLC. CANTOS study demonstrated reduced incidence of NSCLC and decreased lung cancer-related mortality with canakinumab (an IL-1β inhibitor) versus placebo, in dose-dependent manner for patients with atherosclerosis. In preclinical NSCLC humanized models, treatment with canakinumab with or without an anti PD-1 inhibitor demonstrated anti-tumor activity. Combination of canakinumab and pembrolizumab is expected to enhance efficacy of PD-1 inhibition by inhibiting dysregulated inflammation in tumor microenvironment. Based on available evidence, CANOPY-N study was designed to evaluate effect of canakinumab and pembrolizumab as monotherapy or in combination as neoadjuvant treatment for patients with resectable NSCLC.

      Methods

      CANOPY-N (NCT03968419) is a phase II, randomized, open-label study evaluating effect of canakinumab or pembrolizumab monotherapy or in combination as neoadjuvant treatment in resectable NSCLC patients. Patients will be randomized (stratified by histology [squamous/non-squamous]) to receive a total of 2 doses of canakinumab alone or in combination with pembrolizumab or pembrolizumab with safety follow-up up to 130 days from last study drug dose (Figure 1). Patient eligibility criteria is listed in Table 1. Primary endpoint is to determine MPR rate (≤10% of residual viable tumor cells at time of surgery). Secondary endpoints include determination of overall response rate, MPR rate based on local review, surgical feasibility rates, anti-drug antibodies incidence and pharmacokinetic parameters. Surgery-related safety is one of the exploratory endpoints.

      Table 1: Eligibility Criteria

      Key Inclusion Criteria

      Key Exclusion Criteria

      Age ≥18 years

      Histologically confirmed stage IB–IIIA NSCLC

      Eastern Cooperative Oncology Group performance status 0 or 1

      Eligible for surgery, with a planned surgical resection in ~4–6 weeks from the first dose of study treatment

      Availability of archival (if obtained up to 5 months before 1 day of treatment) or new biopsy

      Unresectable or metastatic disease, including brain metastases

      History of severe hypersensitivity reactions to monoclonal antibodies

      Patients who received prior systemic therapy in the past 3 years before screening

      Clinically significant, uncontrolled cardiac disease and/or a recent cardiac event

      Major surgery within 4 weeks prior to randomization

      Figure 1: Study Design

      canopy-n study design.png

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    PL04 - A Vision for Clinical Trials in 2020 and Beyond (Japanese, Mandarin, Spanish Translation Available) (ID 145)

    • Event: WCLC 2020
    • Type: Plenary
    • Track: N.A.
    • Presentations: 1
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      PL04.08 - The Future of Clinical Trials - The Surgical Perspective (ID 3924)

      07:00 - 09:00  |  Presenting Author(s): Masahiro Tsuboi

      • Abstract

      Abstract not provided