507O - EXCLAIM-2: Phase III trial of first-line (1L) mobocertinib versus platinum-based chemotherapy in patients (pts) with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins)+ locally advanced/metastatic NSCLC

Background

Mobocertinib is approved for patients with EGFR ex20ins+ advanced NSCLC following failure of platinum-based chemotherapy, with a manageable safety profile. We report results from EXCLAIM-2 comparing 1L mobocertinib with platinum-based chemotherapy in EGFR ex20ins+ advanced/metastatic NSCLC.

Methods

This open-label, multicenter study (NCT04129502) randomized pts with untreated EGFR ex20ins+ locally advanced/metastatic NSCLC to (1:1) mobocertinib 160 mg PO daily or pemetrexed 500 mg/m² plus cisplatin 75 mg/m²/carboplatin AUC 5 IV every 3 weeks for 4 cycles followed by maintenance pemetrexed. Response was assessed per RECIST v1.1. The primary endpoint was progression-free survival (PFS) assessed by blinded independent review committee (BIRC), with a planned interim analysis (IA) after 184 events.

Results

A total of 354 pts were randomized (mobocertinib 179; chemotherapy 175). Baseline characteristics were balanced between arms. At IA (data cutoff April 4, 2023), BIRC-assessed median PFS was similar between arms (mobocertinib 9.59 mo; chemotherapy 9.63 mo), with BIRC PFS hazard ratio [HR]=1.038 and P=0.803. The study met prespecified futility criteria (BIRC PFS HR >1). BIRC confirmed objective response rates were (mobocertinib/chemotherapy) 32%/30%, confirmed disease control rates were 87%/80%, and median duration of response was 12 vs 8 mo. Grade ≥3 adverse events (AEs) occurred in 62%/53% of pts. Discontinuations due to death (3%/1%) or AEs (10%/14%) were similar between arms (additional safety in the table). Delay in time to deterioration of lung cancer symptoms per EORTC QLQ-LC13 was noted with mobocertinib.

Conclusions

At IA, mobocertinib efficacy was similar but not superior to 1L platinum-based chemotherapy. Safety profiles were similar to previous reports, with no new safety concerns identified. Table: 507O

EXCLAIM-2 safety summary

^a12 pts randomized to chemotherapy did not receive treatment.TEAE, treatment-emergent adverse events.

Clinical trial identification

NCT04129502, 10/16/2019.

Editorial acknowledgement

Professional medical writing assistance was provided by Lauren Gallagher, PhD, of Peloton Advantage, LLC, an OPEN Health company, and funded by Takeda Development Center Americas, Inc.

Legal entity responsible for the study

Takeda Development Center Americas, Inc.

Funding

This study was funded by Takeda Development Center Americas, Inc., Lexington, MA, USA.

Disclosure

P.A. Jänne: Financial Interests, Personal, Other, Consulting: Araxes Pharmaceuticals, ARIAD/Takeda, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Esai, Ignyta, Lilly, Loxo Oncology, Merrimack, Mirati Therapeutics, Pfizer, Roche, Novartis, Nuvalent, Voronoi, Daiichi Sankyo, Silicon Therapeutics, SFJ Pharmaceuticals, Biocartis, Allorion Therapeutics, Accutar Biotech, AbbVie; Financial Interests, Personal, Other, Research Support: Astellas, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Lilly, Puma Biotechnology; Financial Interests, Personal, Stocks or ownership: Gatekeeper, Loxo Oncology; Financial Interests, Personal, Royalties, owned patent on EGFR mutations licensed to LabCorp: Dana-Farber Cancer Institute. M.J. Hochmair: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Amgen, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Roche, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, Roche. S. Peters: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Daiichi Sankyo, Eli Lilly, Merck Serono, Merrimack, Morphotek, Pfizer, Roche, Tesaro; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Clovis Oncology, Daiichi Sankyo, Eli Lilly, Merck Serono, Merrimack, Morphotek, Pfizer, Roche, Tesaro. B. Besse: Financial Interests, Institutional, Research Funding: AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Ignyta, Ipsen, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunotherapeutics, Pfizer, PharmaMar, Roche-Genentech, Sanofi, Servier, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, Tolero Pharmaceuticals. T. Kato: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eli Lilly, Merck Biopharma, MSD, Chugai, Ono, Pfizer, Boehringer Ingelheim, Takeda, AbbVie, Novartis, Taiho, Bristol Myers Squibb, Daiichi Sankyo, Shionogi, Nippon Kayaku; Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Merck Biopharma; Financial Interests, Personal, Research Funding: AstraZeneca, Eli Lilly, Merck Biopharma, MSD, Chugai, Ono, Pfizer, AbbVie, Novartis, Taiho, Bristol Myers Squibb, Regeneron, Amgen; Financial Interests, Personal, Other, Spouse/Financial Dependent: Eli Lilly. D. Nguyen: Financial Interests, Personal, Stocks or ownership: Intuitive Surgical, Teledoc; Financial Interests, Personal, Advisory Role: Janssen Oncology; Non-Financial Interests, Personal, Other: Takeda, Novartis. J. Lin, J. Lin, F. Vranceanu, M. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. R.J. Fram: Financial Interests, Personal, Full or part-time Employment: Takeda; Financial Interests, Personal, Stocks or ownership: Baxter, Bristol Myers Squibb, GE Healthcare, Gilead, Johnson & Johnson, Medtronic, Pfizer, Takeda, Teva, Viatris, Zimmer Binet, Zimvie. T.S.K. Mok: Financial Interests, Personal, Advisory Role: AbbVie, ACEA Pharma, Alpha Biopharma, Amgen, Amoy Diagnostics Co., AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Blueprint Medicines, CStone Pharmaceuticals, Daiichi Sankyo, Eisai, Fishawack Facilitate, GeneDecode, Gritstone Oncology Inc., Guardant Health, Hengrui Therapeutics, Ignyta Inc., IQVIA, Incyte, Janssen, Lilly, Loxo Oncology, Lunit USA, Merck Serono, Merck Sharp & Dohme, Mirati Therapeutics, MORE Health, Novartis, OrigiMed, Pfizer, Puma Biotechnology, Roche, Sanofi-Aventis R&D, Takeda, Virtus Medical Group, Yuhan Corp., SFJ Pharmaceuticals, Curio Science, Inivata, Berry Oncology, G1 Therapeutics Inc., Qiming Development (HK) Ltd., Gilead Sciences, Vertex Pharmaceuticals, Covidien LP, Elevation Oncology, C4 Therapeutics; Financial Interests, Personal, Invited Speaker: ACEA Pharma, Alpha Biopharma Co, Amgen, Amoy Diagnostics, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Fishawack Facilitate, GeneDecode, InMed Medical Communication, Janssen, Lilly, Lunit USA, MD Health, Medscape/WebMD, Merck Serono, MSD, Novartis, OrigiMed, PeerVoice, Physicians’ Education Resource, P Permanyer SL, Pfizer, PrIME Oncology, Research to Practice, Roche, Sanofi-Aventis R&D, Takeda, Touch Medical Media, Daz Group, Lucence Health, Merck Pharmaceuticals HK Ltd., Shanghai BeBirds Translation & Consulting Co, Llangylhul Network Technology Co., Taiho; Financial Interests, Personal, Member of Board of Directors: Lunit USA, AstraZeneca PLC, Hutchison Chi-Med, Act Genomics-Sanomics Group, Aurora; Financial Interests, Personal, Stocks/Shares: Hutchison Chi-Med, Act Genomics-Sanomics Group, Aurora; Financial Interests, Personal, Funding: Clovis Oncology, Xcovery. All other authors have declared no conflicts of interest.