Abstract 567P
Background
The peritoneal cavity is a frequent site of metastasis and recurrence for gynecologic malignancy, which has led to intraperitoneal (IP) administration for traditional cytotoxic chemotherapy. IP immunotherapy is a recognized but under explored area of investigation. The objective of this trial was to determine the recommended phase II dosing (RP2D) of IP-administered nivolumab and ipilimumab in patients with peritoneal carcinomatosis due to gynecologic malignancy.
Methods
In this open-label Phase Ib study (NCT03508570), initial cohorts received IP nivolumab monotherapy (starting dose 1mg/kg escalated to 3mg/kg), followed by cohorts treated with combination nivolumab and ipilimumab (administered IP every 2 and 6 weeks, respectively) guided by a Bayesian design. Maximum combination dose was capped at nivolumab 3mg/kg plus ipilimumab 1mg/kg. Toxicity and response were evaluated using CTCAE v5.0 and modified RECIST v1.1.
Results
23 patients were enrolled; 18 ovarian, 2 endometrial, and 3 with cervical malignancy. The median number of prior lines of therapy was 2 (1-8); one had received prior IP chemotherapy. Median number of cycles was 2 (range 1-7). No DLTs or drug-related SAEs were noted. Grade ≥3 immune related adverse events occurred in 2 (8.7%) patients. One patient developed pancreatitis requiring study discontinuation successfully managed with steroids and the other had asymptomatic pancreatic enzyme elevation. Issues infusing via IP port occurred in 3 patients; all were managed without impacting therapy. There were 16 efficacy-evaluable patients. Partial response was observed in 18.8% (3/16), including 1 patient each with ovarian, endometrial, and cervical cancers. The 7 non-evaluable patients all stopped therapy within the first cycle for progression or death but none had trAE. The median duration of response was 8 months (6-14, two ongoing). An additional 3 patients had stable disease.
Conclusions
The IP administration of nivolumab and ipilimumab is safe, feasible and demonstrated promising preliminary evidence of clinical benefit in advanced gynecologic malignancy. The RP2D based on this study is IP nivolumab 3mg/kg q2wks plus ipilimumab 1mg/kg q6wks.
Clinical trial identification
NCT03508570.
Editorial acknowledgement
Legal entity responsible for the study
The University of Texas MD Anderson Cancer Center.
Funding
Bristol Meyers Squibb.
Disclosure
S. Westin: Financial Interests, Personal and Institutional, Sponsor/Funding, consulting: AstraZeneca, Clovis, GSK, Mereo, Genentech; Financial Interests, Institutional, Sponsor/Funding: Bayer, Cotinga Pharmaceuticals, Novartis; Financial Interests, Personal and Institutional, Sponsor/Funding: OncXerna; Financial Interests, Personal and Institutional, Invited Speaker, consulting: Zentalis; Financial Interests, Personal, Other, consulting: ImmunoGen, eqrx, Lilly, Caris, Vincerx, Mersana, Karyopharm, Merck. A. Sood: Financial Interests, Personal, Other, consulting: Merck, GSK, Kiyatec; Financial Interests, Personal, Stocks/Shares: Biopath. A. Jazaeri: Financial Interests, Institutional, Sponsor/Funding: Iovance, Lilly, Ziopharm, AstraZeneca, Merck, Immatics; Financial Interests, Personal and Institutional, Sponsor/Funding, consulting: BMS, Aravive; Financial Interests, Personal, Other, consulting: Alkermes, Macrogenetics, Obsedian, Nuprobe, Agenus, Instill Bio, Immune-Onc, GSK, Avengebio, EMD-Serono, Gherson Lehrman Group. All other authors have declared no conflicts of interest.