Abstract 1255P
Background
Novel combination immune-oncology strategies aim to improve efficacy while maintaining low toxicity levels. In metastatic gastric cancer (GC), the efficacy of single agent immunotherapy in later lines of treatment is modest. OTSGC-A24 is a cocktail of peptide vaccines against GC specific antigens which induces cytotoxic T lymphocyte (CTL) activity and modulates the intra-tumoral immune contexture. We hypothesize that the combination of OTSGC-A24 and immunotherapy will improve response rates while maintaining low toxicities.
Methods
da VINci is a phase Ib study combining OTSGC-A24 (SC 1mg Q2W) with nivolumab (IV 240mg Q2W) in HLA A*24:02 subtype patients with GC who progressed on ≥1 line of chemotherapy. Patients were immunotherapy naïve. The primary objective was to evaluate safety and dose limiting toxicities (DLT); secondary objectives included response rate (RECIST v1.1) and survival. Serial tumor biopsies were performed prior to treatment, after 4 weeks of the combination, and at progression.
Results
Sixty-eight patients were pre-screened from February 2019 to November 2021, 25 (36.8%) were eligible. Of these, 18 have commenced on treatment. No DLTs were observed. Most frequent all grade toxicities were injection site reactions (n=5 [27.8%], ≥G3=0), fatigue (n=5 27.8%], ≥G3=0), rash (n=5 [27.8%], ≥G3=1), transaminitis (n=3 [16.7%], ≥G3=0), fever (n=3 [16.7%], ≥G3=0). Three patients (16.7%) had partial response (PR), 6 patients (33.3%) had stable disease (SD) while 9 patients (50%) had progressive disease. The median progression-free survival (PFS) was 1.7 months (range 0.4 – 24.2) with a 6-month PFS rate of 27.8% (n=5). The median overall survival (OS) was 3.6 months (range 4.6 – 30.9). Of note, durable clinical benefits were observed in those with SD or PR where the median PFS was 13.1 months (range 2.5 – 24.2) and median OS was 18.6 months (range 2.5 – 30.9).
Conclusions
OTSGC-A24 in combination with nivolumab was well tolerated without any unexpected safety signals. The combination showed promising anti-tumor activity with meaningful durable disease control in metastatic GC patients previously treated with chemotherapy. These results support further investigation in randomized studies. Translational studies are underway.
Clinical trial identification
NCT03784040.
Editorial acknowledgement
Legal entity responsible for the study
National University Hospital Singapore.
Funding
OncoTherapy Science, Inc. (OTS) and Bristol Myers Squibb.
Disclosure
S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, MSD, Amgen, LG biochemical, GSK; Financial Interests, Personal, Invited Speaker: lilly, Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daichii Sankyo; Financial Interests, Institutional, Invited Speaker: Indivumed, zy,meworks, Beigine; Financial Interests, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Invited Speaker, Drug supply for clincal trial: MSD. C.E. Chee: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Guardant Health AMEA; Financial Interests, Personal, Other, Travel accomodations expenses: Taiho. S. Raghav: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, BMS, Roche, Taiho, AstraZeneca; Non-Financial Interests, Advisory Role: Paxman Coolers; Non-Financial Interests, Principal Investigator: MSD. W.P. Yong: Financial Interests, Personal, Advisory Board: Abbvie/Genentech, Amgen, AstraZeneca, Bristol Myers Squibb, Ipsen, Novartis; Financial Interests, Personal, Speaker’s Bureau: Bayer, Eisai, Lilly, MSD Oncology, Sanofi/Aventis, Taiho Pharmaceutical; Financial Interests, Personal, Other, Travel accomodations expenses: Pfizer. All other authors have declared no conflicts of interest.