Abstract 174P
Background
Ivo is a bispecific antibody with cooperative binding to enhance affinity to PD-1 and VEGF, with as yet undefined in IC activity. This analysis assesses IC activity of ivo in pts with BMs at baseline (BL) who received ivo +/- PC as first line systemic therapy for aNSCLC.
Methods
Pts with aNSCLC of any histology, no prior systemic therapy for cancer, and a performance status of 0-1 were eligible for ivo combined with PC or ivo alone on the AK112-201 and AK112-202 trials, respectively, enrolled from 2 centers in China. PC was continued for up to 4 cycles on AK112-201, while ivo continued until progressing disease or up to 2 years in both trials. Initial workup at BL included brain imaging with a brain MRI or head CT with cuts 5mm or smaller to identify BMs; pts with BMs at BL were eligible if without symptoms attributable to BMs. Pts who received pre-study radiotherapy to BMs or who could not undergo follow-up MRI with contrast due to an allergy were not evaluable for IC response. For those with BMs at BL, repeat brain imaging (with a brain MRI every 6 weeks) was pursued while on protocol-based treatment. BMs were evaluated serially by Response Assessment in Neuro-Oncology (RANO) criteria by 2 independent neuroradiologists (US and China) and adjudicated by a third (US-based) as needed.
Results
A combined group of 35 pts met the criteria for inclusion in this analysis: 28 out of 174 on AK112-201, and 7 out of 108 on AK112-202. These pts had a median age of 60 (range 42-68), 77% male, 74% adenocarcinoma/14% squamous/11% other, 46% with PD-L1 >1%. Review of response of BMs across both studies showed 12 pts (34%) achieved an IC response. Of these, 11 had received PC/ivo, among whom 7 achieved an IC complete response (CR); 1 pt achieved an IC CR among the 7 pts who received ivo alone. Median IC progression-free survival was 19.3 months (mo) across both studies (19.3 mo in AK112-201, 16.6 mo in AK112-202). No pts with BMs experienced IC bleeding on or in the 3 mo following ivo +/- PC.
Conclusions
Ivo +/- PC led to IC responses in a subset of pts with previously untreated BMs at BL, including CR in pts receiving ivo with chemo and as monotherapy. Ivo was not associated with IC hemorrhage in these studies.
Clinical trial identification
NCT04736823; NCT04900363.
Legal entity responsible for the study
Akeso.
Funding
Akeso.
Disclosure
L. Zhang: Financial Interests, Institutional, Research Grant: Hengrui, BeiGene, Xiansheng, Eli Lilly, Novartis, Roche, Hansoh, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: MSD, BeiGene, Xiansheng. C. Zhou: Financial Interests, Institutional, Other, Consulting fees: Qilu, Hengrui, TopAlliance Biosciences Inc; Financial Interests, Institutional, Other, Honoraria: Eli Lilly China, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Hengrui, Innovent Biologics, Alice, C-Stone, Luye Pharma, TopAlliance Biosciences Inc, Amoy Diagnostics, AnHeart. H.L. West: Financial Interests, Institutional, Full or part-time Employment: Summit Therapeutics; Financial Interests, Institutional, Other, Consultant: AbbVie, Amgen, AstraZeneca, Eli Lilly, Genentech/Roche, Gilead, Merck, Mirati, Regeneron; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Merck. B. Hu: Financial Interests, Institutional, Full or part-time Employment: Summit Therapeutics. J. Park: Financial Interests, Institutional, Full or part-time Employment: The Radiology Experts. W. Li, J. Yang,Y. Xia: Financial Interests, Institutional, Full or part-time Employment: Akeso Biopharma. All other authors have declared no conflicts of interest.