Proactive management of immune-related hepatic events in a phase II trial of acasunlimab plus pembrolizumab in patients with mNSCLC

Document Type

Conference Proceeding

Publication Date

4-1-2026

Publication Title

ESMO Open

Keywords

acasunlimab, bispecific antibody, C reactive protein, cabozantinib, corticosteroid, cytokine, ferritin, pembrolizumab, procalcitonin, programmed death 1 ligand 1, adult, advisory committee, antimicrobial activity, antineoplastic activity, awareness, cancer inhibition, China, clinical trial, conference abstract, controlled study, cost of travel, event free survival, expert witness, female, human, hypertransaminasemia, immunotherapy, inflammatory disease, ivy, line of treatment, liver, lung cancer, male, mesothelioma, middle aged, multinational corporation, parttime employment, phase 2 clinical trial, premedication, product vigilance, prophylaxis, proportional hazards model, risk factor, travel, young adult

Abstract

Background: Acasunlimab (Aca; DuoBody-PD-L1x4-1BB) is a bispecific antibody immunotherapy designed to reinvigorate antitumor immunity via conditional 4-1BB activation dependent on co-PD-L1 binding. A ph 2 study of Aca in patients (pts) with PD-L1+ mNSCLC (NCT05117242) showed an acceptable safety and efficacy profile. Given historical immune-related risks with 4-1BB agents, proactive management of immune-related risks (PMIR) was implemented. We report the effects of PMIR on mitigation and management of immune-related hepatic adverse events (IRHAEs). Methods: Pts with PD-L1+ mNSCLC and progression on ≥1 prior line of therapy for metastatic disease (including anti–PD-(L)1) received Aca (Arm A) or Aca + pembro combination (Arms B/C). A total of 125 pts were enrolled (84 pre-, 41 post-PMIR). PMIR included enhanced infection monitoring; exclusion of pts with ongoing inflammatory conditions; CRP testing; consideration of HLH/HLH-like syndrome for elevated ferritin and LFT; procalcitonin + cytokine testing for suspected Grade ≥3 immune-related adverse events (IRAEs); management of Grade ≥2 ALT/AST increases with corticosteroids + antimicrobial prophylaxis. Pts with prior IRAEs or Grade 1 transaminase elevations were managed with premedication/dose delays. PMIR effects on risk ratios for IRHAEs were assessed. Cox regression compared time to first Grade ≥3 hepatic event pre- vs post-PMIR. Pts dosed pre-PMIR who remained event-free were censored. Results: Forty-one patients were enrolled post PMIR implementation (Arm B n=9, Arm C n=32). Baseline characteristics were comparable pre- vs post-PMIR (Table). Post-PMIR Grade ≥3 hepatic events decreased from 14.3% to 2.4% (HR [95%CI]: 0.13 [0.02, 0.99]) across all arms. Similar trends were observed in Arm C. [Formula presented] Conclusions: PMIR implementation resulted in lower rates of Grade ≥3 hepatic events in this ph 2 study of Aca, suggesting increased awareness and proactive management may translate to better safety outcomes. Clinical trial identification: NCT05117242. Editorial acknowledgement: Editorial support provided by Cadent, powered by Syneos Health. Legal entity responsible for the study: Genmab A/S. Funding: Genmab A/S. Disclosure: J.G. Aerts: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, CureVac, Nutricia; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Other, Inventor/medical advisor: Amphera; Financial Interests, Personal, Stocks/Shares, value is undetermined: Amphera; Financial Interests, Institutional, Invited Speaker: Pamgene, Eli Lilly, BMS, Novartis, verastem, AstraZeneca, MSD; Financial Interests, Institutional, Royalties, and personal if granted: Amphera; Financial Interests, Institutional, Funding: Nutricia/Danone; Non-Financial Interests, Personal, Member of Board of Directors: Int Ass for the study of Lung Cancer (AISLC, Int Mesothelioma Interest Group; Non-Financial Interests, Personal, Leadership Role, treasurer: IASLC; Non-Financial Interests, Personal, Leadership Role, board member: IMIG. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Amgen, Janssen, GSK, Novartis, Takeda, AbbVie, Gilead, Regeneron; Financial Interests, Personal, Other, Board member: Altum sequencing; Financial Interests, Personal, Other, lectures: AICME; Financial Interests, Personal, Other, Lectures: CCO; Financial Interests, Personal, Expert Testimony: Boehringer; Financial Interests, Personal, Advisory Board, scientific advice: Jazz Pharmaceuticals; Financial Interests, Personal, Member of Board of Directors, spinn off (I have around 8% of stocks): Altum sequencing; Financial Interests, Personal, Member of Board of Directors: Stab therapeutics; Financial Interests, Personal, Ownership Interest, spin-off (10%): Stab Therapeutics; Financial Interests, Personal, Stocks/Shares, co-founde : Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other, Member: AACR, ASCO, ESMO; Financial Interests, Personal, Other, Foundation Board Member: AECC; Financial Interests, Personal, Other, President.ASEICA( Spanish Association of Cancer Research ): ASEICA; Financial Interests, Personal, Other, Foundation president: ONCOSUR; Financial Interests, Personal, Other, member: Small Lung Cancer Group; Non-Financial Interests, Personal, Other, Board member of this anti-cancer Charity: AECC; Non-Financial Interests, Personal, Member, Past-President: ASEICA (Spanish Cancer Research Association); Non-Financial Interests, Personal, Leadership Role, President: Oncosur Foundation. B. Besse: Financial Interests, Personal, Research Grant: AbbVie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Ellipse Pharma, Eisai, Genmab, Genzyme, Hedera Dx, Inivata, Ipsen, Janssen, MSD, PharmaMar, Roche-Genentech, Sanofi, Socar Research, Tahio Oncology, Turning Point Therapeutics. C.F.A. Helissey: Financial Interests, Personal, Other, Honoraria: Janssen, Astellas, Sanofi, AstraZeneca, Bayer, Ipsen, Roche; Financial Interests, Personal, Other, Travel, accommodations, expenses: Janssen. A. Araújo: Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, Novartis, Astellas, BMS, Janssen, Roche, MSD, Sanofi; Financial Interests, Personal, Research Grant: PharmaMar; Astellas, Janssen. D.M. Kowalski: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, MSD, Sanofi-Aventis, Takeda, Pfizer, and Johnson & Johnson. F. Guisier: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, MSD, Roche, Sanofi, Janssen, Pfizer, Takeda; Financial Interests, Institutional, Research Grant: Pfizer, Roche, Takeda. W. Theelen: Financial Interests, Personal, Research Grant: AstraZeneca, MSD and Regeneron to the NKI. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD, Pierre Fabre. S. Gadgeel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Genentech/Roche, Bristol Myers Squibb, Pfizer, Daiichi Sankyo, Lilly, Merck, Gilead, Regeneron, Takeda, Bayer, Astellas, AbbVie, Merck, Johnson & Johnson, Boehringer Ingelheim, Nuvation; Financial Interests, Personal, Other, Data Safety Monitoring Board: AstraZeneca; Financial Interests, Personal, Other, Travel support to attend WCLC 2023 for oral presentation: Mirati, Merck; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Nuvalent, Tango Pharmaceuticals, Genentech/Roche, Genmab, Nimbus, Daiichi Sankyo, Janssen, Amgen, Bayer, Mirati, Pfizer, D3 Bio, Debio Pharma, Arrivent, Grail, Iovance, Jacobio, Kymera, Keza Pharmaceuticals, AbbVie, Amgen, Novita, Regeneron, Turning Point, Verastem, Lilly, Johnson & Johnson, Bristol Myers Squibb International, Beijing Avistone Biotechnology, Debiopharm, Janux, Novita, Prelude Therapeutics, Revolution Medicine; Financial Interests, Personal, Invited Speaker: Arcus. T.C. Wehler: Financial Interests, Personal, Other, Honoraria: Roche, Genentech, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Genentech, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, AbbVie, Merck Serono, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: AstraZeneca, Roche, Genentech, Boehringer Ingelheim; Financial Interests, Personal, Other, Travel expenses: Pfizer, Celgene, Roche, Genentech, Boehringer Ingelheim, AstraZeneca. M.J. Chisamore: Financial Inter sts, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. T. Mark, Y. Zhou, T.J. Ong: Financial Interests, Personal, Full or part-time Employment: Genmab. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech - Roche, GSK, Johnson & Johnson / Janssen, Merck Sharp & Dohme, Regeneron, Pfizer, Daiichi Sankyo, ITeos Therapeutics, Pierre Fabre, PharmaMar, Seagen, Tubulis, Moderna, Ellipses Pharma; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Merck Sharp & Dohme, Pfizer, Eli Lilly, Roche – Genentech, Gilead, Johnson & Johnson / Janssen, Medical Trends, Medscape, PeerVoice; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol-Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Financial Interests, Institutional, Invited Speaker: Nuvalent; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. All other authors have declared no conflicts of interest.

Volume

11

Find It @ Sladen

Share

COinS