1812TiP - IDeate-Lung03: A Phase Ib/II study of ifinatamab deruxtecan (I-DXd) plus atezolizumab (atezo) with or without carboplatin (carbo) as first-line (1L) induction or maintenance in patients (pts) with extensive stage (ES) small cell lung cancer (SCLC)

Background

1L standard-of-care therapy for pts with ES-SCLC includes carbo + etoposide (etop) + atezo but overall survival (OS) is short. B7 homolog 3 (B7-H3) is highly expressed in SCLC; overexpression is associated with poor prognosis. I-DXd, a B7-H3–directed antibody–drug conjugate, demonstrated durable efficacy (objective response rate [ORR] 52.4%; median duration of response [DOR] 5.9 mo; median OS 12.2 mo) in 21 pts with SCLC (median 2 prior lines of therapy) in the phase I/II IDeate-PanTumor01 trial (NCT04145622). We describe IDeate-Lung03, a study investigating I-DXd (given intravenously, once every 3 weeks) + atezo ± carbo as 1L therapy in pts with ES-SCLC.

Trial design

IDeate-Lung03 (NCT06362252) is a multicenter, open-label phase Ib/II trial enrolling ∼149 adult pts with ES-SCLC and ECOG PS ≤1 in the USA, Europe, and Japan. There are 2 parts (Part A: safety run-in; Part B: dose optimization), each with 2 cohorts. Cohort 1 Part A includes pts with no progressive disease (PD) following 4 cycles of 1L induction with carbo + etop + atezo; pts receive I-DXd 12 mg/kg + atezo maintenance. Cohort 2 Part A and both Part B cohorts include treatment-naive pts. In Part A Cohort 2, pts will receive I-DXd 8 mg/kg + atezo + carbo induction followed by I-DXd 8 mg/kg + atezo maintenance; if safety is satisfactory, I-DXd 12 mg/kg + atezo + carbo induction followed by I-DXd 12 mg/kg + atezo maintenance will be tested. Following a Part A safety evaluation, new pts will enroll into Part B and be randomized to receive either carbo + etop + atezo induction followed by I-DXd 8 or 12 mg/kg + atezo maintenance (Cohort 1), or I-DXd 8 or 12 mg/kg + atezo + carbo induction followed by I-DXd 8 or 12 mg/kg + atezo maintenance (Cohort 2). Carbo, etop, and atezo are administered per label. The primary endpoint is safety (including dose-limiting toxicities in Part A). Secondary endpoints are ORR, DOR, disease control rate, clinical benefit rate, time to response, best percent change in sum of diameters of measurable tumors, progression-free survival, OS, pharmacokinetics, and immunogenicity. Part A enrollment is ongoing.

Clinical trial identification

NCT06362252.

Editorial acknowledgement

Medical writing support was provided by Alexandra Mascaro, PhD, of BOLDSCIENCE®, Inc., and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo.

Funding

Daiichi Sankyo, Merck Sharp & Dohme LLC.

Disclosure

C.M. Rudin: Non-Financial Interests, Personal, Advisory Board: Auron, DISCO, Earli; Financial Interests, Personal, Advisory Board: Bridge Medicines, Harpoon Pharmaceuticals; Non-Financial Interests, Personal, Stocks/Shares: Auron, DISCO, Earli. M. Gutierrez: Financial Interests, Personal, Invited Speaker: Guardant Health; Financial Interests, Personal, Other, Consultant: MERCK; Financial Interests, Personal, Advisory Board: Sanofi, Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: COTA Healthcare; Financial Interests, Institutional, Local PI: Merck, BMS, Incyte, NexCure, Pfizer, Roche/Genentech, Boehringer Ingelheim, GSB Pharma, Moderna, Eisai, Silenseed, Seattle Genetics, Regeneron, Sanofi, Johnson & Johnson, MedImmune, Checkpoint Therapeutics, Acerta Pharmaceuticals, Arcus Biosciences, Array BioPharma, Bayer, Celgene, Compass Therapeutics, Constellation Pharmaceuticals, Cyter, EMD Sereno, Fate Therapeutics, GSK, Infinity, Pharmacyclics, Synlogic, Tesaro, Vedanta, IMPACT. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo K.K, Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb Co. Ltd, Eli Lilly Japan K.K, Pfizer, AstraZeneca K.K, Daiichi Sankyo Co.Ltd; Financial Interests, Personal, Royalties, Currently no provided: Sysmex; Financial Interests, Personal, Steering Committee Member: Janssen Pharmaceutical K.K., GSK plc., Daiichi Sankyo, Inc.; Financial Interests, Institutional, Local PI: IQVIA Services JAPAN K.K, Syneos Health Clinical K.K., EPS Corporation., Nippon Kayaku Co.,Ltd., Takeda Pharmaceutical Co.,Ltd., MSD K.K., Amgen Inc., Taiho Pharmaceutical Co.,Ltd., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Kobayashi Pharmaceutical Co., Ltd., Pfizer Japan Inc., AbbVie Inc., A2 Healthcare Corp., Eli Lilly Japan K.K., Medpace Japan KK, EPS International Co.,Ltd,., Covance Japan Inc., EP-CRSU CO., LTD., GSK K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., PRA Health Sciences Inc., Astellas Pharma Inc., Ascent Development Services, AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Novartis Pharma K.K., Merck Biopharma Co., Ltd, Mochida Pharmaceutical Co., Ltd., Japan Clinical Research Operations; Financial Interests, Institutional, Research Grant: Japanese Gastric Cancer Association, Clinical Research Support Center Kyushu, Japan Clinical Cancer Research Organization, Ono Pharmaceutical Co., Ltd., Medical Research Support, Eisai Co., Ltd, Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Bayer Yakuhin, Ltd, Kyowa Kirin Co.,Ltd.; Financial Interests, Institutional, Funding: SRL Medisearch Inc., Eisai Inc., Thoracic Oncology Research Group(TORG), West Japan Oncology Group (WJOG), Comprehensive Support Project for Oncological Research of Breast Cancer (CSPOR-BC), Mebix, Inc.; Non-Financial Interests, Member: West Japan Oncology Group, Japanese Society of Medical Oncology. J. Thompson: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: GE Healthcare, Regeneron. M. Arca: Financial Interests, Personal, Full or part-time Employment, Project lead: Daiichi Sankyo. D. Hirose: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Singh: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Turner: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. T.K. Owonikoko: Financial Interests, Personal, Advisory Board: Novartis, Lilly, Eisai, Bristol-Myers Squibb, Amgen, AstraZeneca, Boehringer Ingelheim, EMD Serono, Bayer, Roche/Genentech, Merck, Oncocyte, Takeda, Jazz Pharmaceuticals, Daiichi Sankyo, Janssen, BieGene, Genentech, Coherus Biosciences, GenCart, Hear Biologics, Meryx, Puma Biosciences, GSK, Gilead, Regeneron, Betta Pharmaceuticals, OncoHost, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Research Grant: Amgen Inc, AstraZeneca, Bayer, Bristol Myers Squibb, Cardiff Oncology, Eisai, Roche/Genentech, Merck, Novartis, Oncorus, Pfizer, Turning Point Theraputics, Y-mAbs Theraputics, Daiichi Sankyo, Puma Biosciences, Cyclacel, GSK, Boehringer Ingelheim; Financial Interests, Personal, Other: Coherus Biosciences, GenCART, Cambium, Taobob. All other authors have declared no conflicts of interest.