Abstract 988P
Background
Mobocertinib (TAK-788) is an oral tyrosine kinase inhibitor selectively targeting epidermal growth factor receptor gene (EGFR) ex20ins+ non–small cell lung cancer (NSCLC). In a Phase 1/2 trial, mobocertinib demonstrated clinical activity in PPP with EGFR ex20ins+ mNSCLC (Nov 1, 2020 data cutoff; Zhou, JAMA Oncol. 2021;7(12):e214761).
Methods
This 3-part, open-label study (NCT02716116) consisted of dose-escalation and dose-expansion cohorts, as well as an extension cohort (EXCLAIM). Patients with EGFR ex20ins+ mNSCLC, Eastern Cooperative Oncology Group status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease received mobocertinib 160 mg QD. Primary endpoint was confirmed objective response rate (cORR; RECIST v1.1) per independent review committee (IRC). We present updated efficacy and safety data for the PPP cohort.
Results
Results are from Nov 1, 2021 (data cutoff), ∼24 mo after last patient enrollment (median follow-up: 25.8 mo). In the PPP cohort (n=114), median age was 60 years (range: 27–84 years), 66% of patients were female, 60% were Asian, and 59% had received ≥2 prior systemic anticancer lines. The cORR was 28.1%, median duration of response was 15.8 mo, and median progression-free survival was 7.3 mo (all per IRC; Table). Confirmed responses were observed in all prespecified subgroups. The most common treatment-related adverse events (TRAEs) were diarrhea (92%), rash (46%), paronychia (38%), decreased appetite (37%), nausea (34%), vomiting (32%), and dry skin (31%). The only Grade ≥3 TRAE observed in ≥10% of patients was diarrhea (23%). The only AE leading to discontinuation in >2% of patients was diarrhea (4%). Table: 988P
| PPP Cohort (n=114) | |
| Median follow-up [95% CI], mo | 25.8 [24.6–26.7] |
| Confirmed ORR, n (%) [95% CI] Per IRC Per INV | 32 (28) [20–37] 40 (35) [26–45] |
| DCR, n (%) [95% CI] Per IRC Per INV | 89 (78) [69–85] 89 (78) [69–85] |
| Median DORa, mo [95% CI] Per IRC Per INV | 15.8 [7.4–19.4] 13.9 [5.6–19.4] |
| Median PFSa, mo [95% CI] Per IRC Per INV | 7.3 [5.5–9.2] 7.3 [5.6–8.8] |
| Median OSa, mo [95% CI] 12-mo ratea, % 18-mo ratea, % | 20.2 [14.9–25.3] 70 55 |
DCR, disease control rate; DOR, duration of response; INV, investigator; OS, overall survival; PFS, progression-free survival. a Per Kaplan-Meier method.
Conclusions
At more than 2 years of follow-up in the Phase 1/2 trial, mobocertinib continues to demonstrate clinically meaningful benefit for PPP with EGFR ex20ins+ mNSCLC, with a manageable safety profile.
Clinical trial identification
NCT02716116.
Editorial acknowledgement
Professional medical writing assistance was provided by Amy Zannikos, PharmD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Takeda Development Center Americas, Inc., Lexington, MA, USA.
Legal entity responsible for the study
Takeda Development Center Americas, Inc., Lexington, MA, USA.
Funding
Takeda Development Center Americas, Inc., Lexington, MA, USA.
Disclosure
S.S. Ramalingam: Financial Interests, Institutional, Other, Consultant: Amgen, BMS, Merck, AstraZeneca, Takeda, Eisai, Daiichi Sankyo, GSK; Financial Interests, Personal, Other, Editor in Chief, CANCER journal: American Cancer Society; Financial Interests, Research Grant: Merck, AstraZeneca, Advaxis, BMS, Amgen, Takeda, Genmab, GSK. C. Zhou: Financial Interests, Personal, Invited Speaker, Honoraria: Eli Lily, Roche, Sanofi, Qilu Pharma, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, Top Alliance Biosciences Inc; Financial Interests, Personal, Invited Speaker, BI: BI; Financial Interests, Personal, Invited Speaker, MSD: MSD; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnostics. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Janssen, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer Ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, Regeneron, Genmab, Bayer. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis, AstraZeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Member: ASCO. G.J. Riely: Financial Interests, Personal, Other, Travel: Merck, Sharp & Dohme; Financial Interests, Institutional, Funding: Novartis, Roche/Genentech, Millennium, GSK, Pfizer, Infinity Pharmaceuticals, Ariad, Mirati Therapeutics, Merck. T. Mekhail: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BMS, Lilly, Merck, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly. D. Nguyen: Financial Interests, Personal, Other, Stock and other ownership interests: Intuitive Surgical, Teledoc; Financial Interests, Personal, Other, publication fees: Takeda. M.R. Garcia Campelo: Financial Interests, Personal, Other, Honoraria: Honoraria ; Financial Interests, Personal, Other, speakers bureau and/or advisory role: Takeda, AstraZeneca, Roche, Pfizer, BMS, Boehringer Ingelheim, Janssen, Novartis, MSD. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Merck Sharp & Dohme, Pfizer, Sanofi, Takeda, Merck Serono, Peptomyc, F. Hoffmann-La Roche, Novartis, Daichii Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, Takeda, TouchOncology; Financial Interests, Institutional, Other, grant for Oncology Innovation: Merck Healthcare KGAa; Financial Interests, Institutional, Other: Fundación Merck Salud; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). D. Misch: Financial Interests, Personal, Other, Consulting/advisory role: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, MSD, Novartis, Roche, Sanofi; Financial Interests, Institutional, Other, Consulting/advisory role: Takeda. M. Kaur: Financial Interests, Personal, Full or part-time Employment: Takeda. V. Bunn: Financial Interests, Personal, Full or part-time Employment: Takeda. M. Lin: Financial Interests, Personal, Full or part-time Employment: Takeda. P. Zhang: Financial Interests, Personal, Full or part-time Employment: Takeda. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Transcenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Allorion Therapeutics, Accutar Biotech, AbbVie; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics; Financial Interests, Personal, Royalties, I receive post-marketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, Puma, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology.