1787P - Intracranial response in patients (pts) with baseline (BL) brain metastases (BM) and extensive-stage (ES) small cell lung cancer (SCLC) treated with ifinatamab deruxtecan (I-DXd) in the IDeate-Lung01 study

Background

Around 50–80% of pts with SCLC develop BM. Antibody–drug conjugates (ADCs) containing the DXd payload (T-DXd, HER3-DXd, and Dato-DXd) have shown encouraging intracranial responses. I-DXd, a B7 homolog 3–directed ADC, demonstrated promising efficacy in pts with ES-SCLC in the ongoing global phase II IDeate-Lung01 study (NCT05280470). We report I-DXd CNS efficacy in pts with BL BM in the dose-optimization part of IDeate-Lung01.

Methods

Pts with ES-SCLC and 1–3 prior lines of therapy, including platinum-based chemotherapy, were enrolled. Pts with asymptomatic BM (treated or untreated) were eligible. Pts received intravenous I-DXd 8 or 12 mg/kg Q3W. Brain imaging was performed at BL and end of treatment, and for pts with BL BM (≥1 target and/or non-target CNS lesion), Q6W for 36 weeks and Q12W thereafter. The primary endpoint was ORR per RECIST 1.1 by blinded independent central review (BICR). Central nervous system (CNS) response (neuroradiologist-reviewed brain imaging) was assessed by BICR per CNS RECIST.

Results

Overall, 37 (42%) of 88 pts had BL BM. At data cutoff (July 25, 2023), CNS cORR was 38% among all pts with BL BM and 56% among 16 pts with brain target lesions (Table). CNS ORR among 21 pts who did not receive brain radiotherapy (RT) for BL BM was 33% (5/15 pts) and 50% (3/6 pts) with I-DXd 8 and 12 mg/kg, respectively. Among pts with BL BM, 3/21 pts (14%) without BL brain RT had progression in the brain, vs 4/16 (25%) pts with BL brain RT. In pts with BL BM, 35% had Grade ≥3 TEAEs (47% in pts without BL BM), and 8% had a TEAE associated with study drug discontinuation (12% in pts without BL BM). Data, including systemic efficacy (which was similar between pts with and without BL BM), will be presented from an updated cutoff. Table: 1787P

CI, confidence interval; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease.

Conclusions

CNS responses with I-DXd appear consistent with those seen with other DXd ADCs, with promising intracranial efficacy in ES-SCLC pts who have a poor prognosis.

Clinical trial identification

NCT05280470.

Editorial acknowledgement

Medical writing support was provided by David Buist, 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

M.L. Johnson: Financial Interests, Institutional, Research Funding: AbbVie, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, ArriVent BioPharma, Artios Pharma, AstraZeneca, Atreca, Bayer, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Dynavax, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchison MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals / Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Taiho Oncology, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics; Financial Interests, Institutional, Advisory Role: AbbVie, Alentis Therapeutics, Amgen, Arcus Biosciences, Arrivent, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech / Roche, Genmab, Gilead Sciences, Gritstone Oncology, Hookipa Biotech, Immunocore, Janssen, Jazz Pharmaceuticals, Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Normunity, Novartis, Novocure, Pfizer, Pyramid Biosciences, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, VBL Therapeutics, Zai Laboratory. P.F. Simoes da Rocha: Other, Congress and travel: MSD, BMS, AstraZeneca, Kyowa Kirin. Y. Chen: Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Merck, Junshi Biosciences, Genmab, Genentech, AbbVie, Lilly; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca, Amgen, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Amgen, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Takeda, Guardant Health, Jazz Pharmaceutical. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, Beigene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati, Boehringer; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Personal, Other, spinn off (I have arounfd 8% of stocks): Altum sequencing; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President. ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group; Non-Financial Interests, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Leadership Role, President: Oncosur Foundation. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Family member is an employee: AstraZeneca. C. Hann: Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo, Amgen, AbbVie; Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Puma BioTechnology, Janssen. M. Nishio: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, Lilly, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, BORONOI. M. Qian: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Tang: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Godard: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Singh: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. C.M. Rudin: Non-Financial Interests, Personal, Advisory Board: Auron, DISCO, Earli; Non-Financial Interests, Personal, Stocks/Shares: Auron, DISCO, Earli; Financial Interests, Personal, Advisory Board: Bridge Medicines, Harpoon Pharmaceuticals. All other authors have declared no conflicts of interest.