1018P - Leveraging innate and adaptive immunity with AFM24 and atezolizumab in metastatic gastric cancer

Background

Patients (pts) with relapsed, metastatic Gastric Cancer (mGC) have limited therapeutic options. AFM24, a bispecific EGFR/CD16A-targeting innate cell engager redirects and enhances the innate and indirectly the adaptive immune response against EGFR-expressing tumors. Atezolizumab, a PD-L1 inhibitor, potentiates the adaptive immune response. This Phase 1/2a study (NCT05109442) is evaluating synergistic activity of AFM24 and atezolizumab against EGFR-expressing solid tumors. Phase 1 showed initial signs of activity in a patient with signet ring cell mGC after 2 doses with a partial response (PR) lasting ∼8 months. Here we present data from the mGC expansion cohort.

Methods

Patients with mGC or metastatic Gastroesophageal Junction Cancer (mGEJC) progressed on ≥1 line of therapy received I.V. doses of 480 mg AFM24 weekly and 840 mg atezolizumab fortnightly. The primary endpoint was overall response rate by investigator assessment (RECIST v1.1). Secondary endpoints included safety, pharmacokinetics and immunogenicity. Treatment was given in four-week cycles (C) until disease progression, intolerable toxicity, investigator discretion or patient withdrawal of consent. Tumor assessments were performed at screening and every 2 C.

Results

As of 2nd April 2024, 12 pts with mGC/mGEJC received AFM24 and atezolizumab for a mean duration of 15.5 (6-43) weeks. Median age was 57.5 (51-74) years, 75% pts were male. All pts had PS-ECOG 0-1. Median number of prior lines was 2.5 (1-5). The combination has a manageable safety profile. The most common AFM24-related adverse event was infusion related reaction in 9/12 pts (8 G1/2, 1 G3).Three patients achieved a PR, one of them confirmed, after initial stable disease (SD) at C4, C6 and C8, respectively. From these, one of them had a tumor mutational burden of 11.94 and was previously treated with a PD-1 inhibitor and two pts had signet ring cell mGC.

Conclusions

AFM24 plus atezolizumab showed early signs of activity in relapsed/refractory mGC/mGEJC pts, including patients with signet ring cell gastric adenocarcinoma. No new or unexpected toxicities were reported. This chemotherapy-free approach could be a therapeutic alternative and warrants further study.

Clinical trial identification

NCT05109442.

Editorial acknowledgement

Legal entity responsible for the study

Affimed GmbH.

Funding

Affimed GmbH.

Disclosure

O. Saavedra Santa Gadea: Financial Interests, Principal Investigator: Affimed GmbH. A. Oberoi: Financial Interests, Other, Sub-investigator: Affimed GmbH. J.S. Lopez: Financial Interests, Personal, Advisory Board: Roche Genentech, Basilea, Ellipses Pharma, Cureteq, Pierre Faber, GSK; Financial Interests, Institutional, Research Grant: Roche Genentech, Basilea, Astex. A. Cervantes: Financial Interests, Institutional, Advisory Board: Merck Serono, Amgen, Roche, Transgene, AnHeart Therapeutics, AbbVie, GSK; Financial Interests, Institutional, Invited Speaker: Amgen, Roche, Merck Serono, Foundation Medicine; Financial Interests, Personal, Other, Associate Editor: Annals of Oncology, ESMO Open; Financial Interests, Personal, Other, Editor in Chief: Cancer Treatment Reviews; Financial Interests, Institutional, Research Grant, Principal Investigator: Actuate Therapeutic, Amgen, Astellas Pharma, BeiGene, Bayer, AstraZeneca, BMS, Amcure, FibroGen, Lilly, Genentech, MedImmune, Merck Serono, Novartis, Natera, MSD, Servier, Sierra Oncology, Adaptimmune, Takeda, Affimed, Roche, Seamless, Gilead, Janssen, F. STAR Therapeutics, Ribon Therapeutics; Non-Financial Interests, Other, Scientific Director: INCLIVA Biomedical Research Institute. M. Ponz-Sarvise: Financial Interests, Personal, Advisory Board: Taiho, AstraZeneca; Financial Interests, Institutional, Funding: Roche, Novocure; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Other, imFLAME Committee member: Roche. H.R. Kim: Financial Interests, Other, pre-clinical research collaboration: Affimed GmbH; Financial Interests, Principal Investigator: Affimed GmbH. A.B. El-Khoueiry, B. Shim, J.W. Kim, V. Boni, C. Szczylik, W. Rogowski, S. Mandziuk, R. Ramlau: Financial Interests, Local PI: Affimed GmbH. I. Lugowska: Financial Interests, Coordinating PI: Affimed GmbH. U. Gaertner, D. Schütz, M. Emig: Financial Interests, Stocks/Shares: Affimed GmbH; Financial Interests, Full or part-time Employment: Affimed GmbH. S. Lutkewitz: Financial Interests, Stocks or ownership: Affimed GmbH; Financial Interests, Full or part-time Employment: Affimed GmbH. D. Morales-Espinosa: Financial Interests, Personal, Full or part-time Employment: Affimed GmbH; Financial Interests, Personal, Stocks/Shares: Affimed GmbH.