Abstract CT221: Phase II of frontline maintenance rucaparib in combination with nivolumab in ES SCLC
Authors: Chauhan Aman , Kolesar Jill , Yan Donglin , Hao Zhonglin , McGarry Ronald , Villano John , Zinner Ralph , Maskey Ashish , Miller Jordan , Mullett Timothy , Khurana Aman , Zhou Xitong , Gupta Garima , Flora Daniel , Darnell Colleen , O'Neil Richard , Kunos Charles , Evers Mark B. , Anthony Lowell , Arnold Susanne 
Published: April 2023

Abstract
Purpose: Immune checkpoint inhibitor (ICI) maintenance therapy is standard of care for frontline management of extensive stage small cell lung cancer (ES SCLC). However, overall survival benefit of addition of ICI maintenance to frontline ES SCLC treatment is modest and further improvement is needed. We hypothesized that addition of poly (ADP-ribose) polymerase inhibition to ICI maintenance therapy for patients with platinum sensitive ES SCLC could improve antitumor efficacy of ICI.
Methods: A single-arm, investigator-initiated phase II trial (NCT03958045) enrolled patients with platinum sensitive ES SCLC who received frontline maintenance nivolumab 480 mg IV every 4 weeks, and rucaparib, 600 mg PO twice a day after completion of 4-6 cycles of platinum doublet. The primary outcome was median progression free survival. Secondary endpoints included assessment of objective response and adverse effects (AEs) per CTCAE 5.0. Correlative studies included pretreatment and during-treatment immune assays and circulating tumor DNA TP53 mutation status.
Results: A total of 42 patients were consented and 33 met eligibility criteria and were treated. All patients received 4-6 cycles of frontline platinum doublet and had at least a partial response by RECIST at the time of enrollment. In the 33 participants, the most common grade 3 and 4 AEs (at least possibly related) were hypokalemia (3%), hyponatremia (3%), elevated alanine aminotransferase (3%), neutropenia (3%) and leukocytopenia (3%). No grade 5 AE was noted. The median PFS (mPFS) was 3 months from time of enrollment on frontline maintenance (post platinum doublet). The mPFS was 11 months from cycle 1 of platinum doublet. Overall, 89.8% patients were alive at 12 months and 54.4 % patients were alive at 24 months from the start of platinum doublet. Currently 2 patients are on active treatment and other two have completed study treatment and are on observation with stable disease.
Conclusions: Maintenance rucaparib combined with immune checkpoint inhibition was tolerable and showed promising activity after completion of frontline chemotherapy in platinum sensitive extensive stage small cell lung cancer patients.
Citation Format: Aman Chauhan, Jill Kolesar, Donglin Yan, Zhonglin Hao, Ronald McGarry, John Villano, Ralph Zinner, Ashish Maskey, Jordan Miller, Timothy Mullett, Aman Khurana, Xitong Zhou, Garima Gupta, Daniel Flora, Colleen Darnell, Richard O'Neil, Charles Kunos, Mark B. Evers, Lowell Anthony, Susanne Arnold. Phase II of frontline maintenance rucaparib in combination with nivolumab in ES SCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT221.