Brad Nakamura ¹ Rosemary Senguttuvan ^1* Nora Ruel ² Paul H. Frankel ^2* Susan Yost ³ Sarah Cole ⁴ Sue Chang ⁵ Alexander Jung ^6* Melissa Eng ^1* Raechelle Tinsley ^1* Daphne Stewart ^3* Edward W. Wang ³ Joshua Cohen ^1* Jeannine Villella ^7* Richard L. Whelan ^7* Amit Merchea ⁸ Danielle K. DePeralta ^7* Mihaela C. Cristea ⁹ Mark Wakabayashi ⁹ Mustafa Raoof ¹ Thanh H. Dellinger ^1*

• ¹ Department of Surgery, City of Hope National Medical Center, Duarte, United States
• ² Department of Computation and Quantitative Medicine, City of Hope National Medical Center, Duarte, California, United States
• ³ Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, United States
• ⁴ Clinical Protocol Development, City of Hope National Medical Center, Duarte, California, United States
• ⁵ Department of Pathology, City of Hope National Medical Center, Duarte, California, United States
• ⁶ Department of Diagnostic Radiology, City of Hope National Medical Center, Duarte, California, United States
• ⁷ Department of Surgery, Northwell Health, New York, New York, United States
• ⁸ Department of Surgery, Mayo Clinic Florida, Jacksonville, Florida, United States
• ⁹ Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States

Introduction: Low grade serous ovarian carcinoma (LGSOC) is a rare subtype of ovarian cancer (OC) that is challenging to treat due to its relative chemoresistance. Given that LGSOC patients often recur in the peritoneal cavity, novel intraperitoneal (IP) chemotherapy should be explored. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a method that has demonstrated peritoneal disease control in cancers with peritoneal metastases. Methods: NCT04329494 is a US multicenter phase 1 trial evaluating the safety of PIPAC in recurrent ovarian, uterine, and GI cancers with peritoneal metastases. This analysis describes the outcomes of a sub-cohort of four LGSOC patients treated with IP cisplatin 10.5 mg/m2, doxorubicin 2.1 mg/m2 PIPAC q4-6 weeks. Primary endpoints included dose-limiting toxicities (DLT) and incidence of adverse events (AE). Secondary endpoints were progression free survival (PFS) and treatment response based on radiographic, intraoperative, and pathological findings. Results: Four patients with LGSOC were enrolled of which three were heavily pretreated. Median prior lines of therapy was 5 (range 2-10). Three patients had extraperitoneal metastases, and two patients had baseline partial small bowel obstructive (SBO) symptoms. Median age of patients was 58 (38-68). PIPAC completion rate (≥2 PIPACs) was 75%. No DLTs or Clavien-Dindo surgical complications occurred. No G4/G5 AEs were observed, and one G3 abdominal pain was reported. One patient had a partial response after 3 cycles of PIPAC and completed an additional 3 cycles with compassionate use amendment. Two patients came off study after 2 cycles due to extraperitoneal progressive disease. One patient came off study after 1 cycle due to toxicity. Median decrease in peritoneal carcinomatosis index between cycles 1 and 2 was 5.0%. Ascites decreased in 2 out of 3 patients who had ≥2 PIPACs. Median PFS was 4.3 months (1.7-21.6), median overall survival was 11.6 months (5.4-30.1), and objective response rate was 25%. Conclusion: PIPAC with cisplatin/doxorubicin is well tolerated in LGSOC patients without baseline SBO symptoms. IP response was seen in 2 out of 3 patients that completed ≥2 PIPAC cycles. Further study of PIPAC for patients with recurrent disease limited to the IP cavity and with no partial SBO symptoms should be considered.