Abstract CT157: Phase IB study of nivolumab and veliparib in patients with advanced solid tumors and lymphoma with and without alterations in selected DNA repair genes
Authors: Vagia Elena , Viveiros Pedro , Kang Cyra-Yoonsun , Kalyan Aparna , Nelson Valerie , Mahalingam Devalingam , Chae Young Kwang 
Published: September 2020

Abstract
Background: Genomic alterations in DNA repair genes is associated with genomic instability and increase tumor mutation burden. PARP inhibitors including veliparib and PD-1 inhibitors including nivolumab are effective in tumors harboring DNA Damage Repair (DDR) deficiency and high TMB, respectively. Methods: We conducted a phase Ib study to evaluate the safety and efficacy of nivolumab and veliparib in patients with advanced solid tumors or aggressive lymphoma. Study population included patients with advanced malignancies who had progressed at least in one prior line of treatment and had adequate kidney and liver function. All patient had genomic profiling of the tumor prior to enrollment demonstrating at least one mutation in selected DNA repair genes. Nivolumab was administered 240 mg on D1 and D15 every 28 days for the first 4 cycles and continued 480 mg monthly thereafter. Veliparib was administrated orally in a two-stage dose escalation. Three patient received 300 mg BID with no evidence of dose limiting toxicities allowing to increase the dose to 400 mg BID. Primary endpoints were to assess tolerability of nivolumab and veliparib combination and also to determine maximum tolerated dose (MTD). Secondary endpoint was to evaluate objective response rate (ORR). Results: From May 2017 through August 2019, 15 patients with advanced malignancies meeting the eligibility criteria were enrolled in the study. The first three patients received the lower dose of veliparib, 300 mg BID. None of those had dose limited toxicity so the dose of veliparib increased to 400 mg BID. Three more patient received 400 mg BID with no unacceptable toxicity concluding that the MTD of veliparib to be 400 mg. All subsequent patient received the MTD of veliparib. The combination of veliparib 400 mg BID and nivolumab either 240 mg every two weeks or 480 mg monthly was reasonably well tolerated. Grade 3-4 adverse events occurred in 7 patients with the most common being anemia and fatigue. ORR and survival data were assessed for 14 patient, 1 patient denied treatment after screening and withdrew the informed consent. No response was observed. Of note, a patient with pancreatic cancer harboring BRIP1 mutation received 12 cycles of treatment (24 weeks) without disease progression. PFS and OS were 9.0 and 26.8 weeks, respectively. Discussion: Combination of nivolumab and veliparib is a very well tolerated regimen. Even though this study did not meet its primary endpoint in response evaluation, we observed a durable stabilization of disease in two patients with pancreatic cancer with and without mutations in DDR genes. Further large-scale clinical studies are warranted to evaluate the efficacy of combination treatment with immunotherapy and PARP inhibitor and to identify biomarkers that predict response to such treatment.
Citation Format: Elena Vagia, Pedro Viveiros, Cyra-Yoonsun Kang, Aparna Kalyan, Valerie Nelson, Devalingam Mahalingam, Young Kwang Chae. Phase IB study of nivolumab and veliparib in patients with advanced solid tumors and lymphoma with and without alterations in selected DNA repair genes [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT157.