1550P - Evaluating the novel combination of pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) as an immunomodulator in combination with systemic nivolumab for gastric cancer peritoneal metastases

Background

Combination therapies with immunomodulators and systemic immune checkpoint inhibitors (ICIs) may overcome cancer resistance to immunotherapy. In gastric cancer patients with peritoneal metastases (GCPM), PIPAC-OX has been shown to induce direct DNA-damage and immunogenic cell death but has not been evaluated in combination with ICIs. We conducted a phase I study, evaluating the safety and efficacy of PIPAC-OX in combination with systemic nivolumab.

Methods

Patients with predominant GCPM who had progressed on at least 1^st -line systemic chemotherapy were recruited across 3 centers in Singapore and Belgium. After initial staging laparoscopy, patients received PIPAC oxaliplatin at 90mg/m2 every 6 weeks with intravenous nivolumab at 240mg every 2 weeks, up to disease progression or death. Response was evaluated clinically by Peritoneal Carcinomatosis Index (PCI) and Response Evaluation Criteria in Solid Tumors (RECIST), while histological response was determined with the Peritoneal Regression Grading Score (PRGS).

Results

In total, 18 patients with GCPM were prospectively recruited and underwent a combined total of 32 cycles of PIPAC with a median follow-up of 7.1 months. The first cycle of PIPAC was successfully administered in all patients while 50% (9/18), and 28% (5/18) received 2 & 3 cycles respectively. Common adverse events included abdominal pain and diarrhea while three (9.4%) PIPAC-related severe adverse events including diarrhea and transaminitis were reported. Objective response was seen in 7.1% while disease control was achieved in 57.1% of patients. The median PCI decreased by 5 and 7 points, while PRGS grade 1-2 response was seen in 67% and 100% at 2^nd & 3^rd PIPAC respectively. Those that received 3 PIPACs had a median OS of 19.8m (vs 2.9m for 1 PIPAC, p = 0.01).

Conclusions

PIPAC-OX in combination with systemic nivolumab was safe and tolerable, with some responses seen. Ongoing biomarker and translational analyses may yield further insights into the unexpected long-term responders and define the subgroup most likely to benefit from combination locoregional and systemic therapy for GCPM.

Clinical trial identification

NCT03172416.

Editorial acknowledgement

Legal entity responsible for the study

National University Hospital, Singapore.

Funding

National Medical Research Council, Singapore.

Disclosure

R. Sundar: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD, GSK, DKSH, Astellas; Financial Interests, Personal, Invited Speaker: MSD, Eli Lilly, BMS, Roche, Taiho, AstraZeneca, DKSH, Ipsen; Financial Interests, Personal, Stocks/Shares: Teladoc; Financial Interests, Institutional, Invited Speaker: Paxman Coolers; Financial Interests, Personal and Institutional, Invited Speaker: Taiho, MSD, BMS, Novartis; Non-Financial Interests, Advisory Role: Paxman Coolers; Non-Financial Interests, Principal Investigator: MSD, Natera. K. Geboes: Financial Interests, Institutional, Advisory Board: BMS, MSD, Servier, Ipsen; Financial Interests, Institutional, Speaker’s Bureau: BMS, MSD, Servier. M.C.H. Ng: Other, Personal, Advisory Board: MSD; Non-Financial Interests, Personal, Other, Honoraria: BMS. W.P. Yong: Financial Interests, Personal, Invited Speaker: DKSH Singapore Pte Ltd, AstraZeneca Singapore Pte Ltd., Bristol Myers Squibb, MSD Pharma (Singapore) Pte Ltd, Novartis (S) Pte Ltd; Financial Interests, Personal, Advisory Board: Ipsen Pharma Singapore Pte Ltd, Amgen; Financial Interests, Institutional, Local PI: Novartis (S) Pte Ltd, Amgen. All other authors have declared no conflicts of interest.