The final analysis of a phase I/II study of nivolumab, ipilimumab combined with nintedanib in advanced non-small cell lung cancer.

person Sonam Puri Huntsman Cancer Institute, University of Utah, Salt Lake City, UT info_outline Sonam Puri, Tawee Tanvetyanon, Ben C. Creelan, Michael Rahman Shafique, Andreas Nicholas Saltos, Alberto Chiappori, Eric B. Haura, Ram Thapa, Dung-Tsa Chen, Theresa A. Boyle, Scott Joseph Antonia, Jhanelle Elaine Gray

Authors person Sonam Puri Huntsman Cancer Institute, University of Utah, Salt Lake City, UT info_outline Sonam Puri, Tawee Tanvetyanon, Ben C. Creelan, Michael Rahman Shafique, Andreas Nicholas Saltos, Alberto Chiappori, Eric B. Haura, Ram Thapa, Dung-Tsa Chen, Theresa A. Boyle, Scott Joseph Antonia, Jhanelle Elaine Gray Organizations Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, Moffitt Cancer Center, Tampa, FL, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Duke Cancer Institute, Durham, NC Abstract Disclosures Research Funding Other Drug support BI, BMS, Other support: Florida Department of Health James and Esther King Grant Background: Nintedanib (NT) is an oral triple kinase inhibitor that is active against NSCLC and inhibits the activity of the immunosuppressive cancer associated fibroblasts in the tumor microenvironment (TME). Targeting the TME with NT may represent an important synergistic approach in improving immunotherapy (IO) outcomes for NSCLC. We initiated a phase Ib/II trial to evaluate the combination of NT, nivolumab (N) and ipilimumab (I) in advanced (a)NSCLC. Based on the phase IB (dose escalation) results, the combination of N (3mg/kg/2w), I (1mg/kg/6w) and NT (150mg once daily) was declared as the recommended phase 2 dose (RP2D). Here we present the final analysis of the regimen in treatment naïve (TN), and IO pretreated (IP) aNSCLC. Methods: This is a single institution, non- randomized, parallel assignment phase I/II clinical trial of aNSCLC pts. Eligible pts were TN (Arm A) or with disease progression following IO (Arm B) with planned sample size of 40/arm. Enrollment into phase II was by the Bayesian two-stage design method with the primary objective of determining the overall response rate (ORR) in the intent to treat population. Key secondary objectives were overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize demographic and safety data. The Kaplan- Meier method with log-rank test (5% level of significance, 95% CI and 2-sided test) was used for survival analysis. Results: 22 and 29 pts received the N+I+NT at the RP2D in Arm A and B, respectively. The median age was 67 [42;92] with 53% (27/51) females, 84% (42/51) Caucasian, ECOG 1 in 88% (45/51), and a current/prior history of tobacco use in 88% (45/51) pts. Adenocarcinoma histology was common (64%, 33/51) with PD-L1 ≥1% in 52% (22/42) pts. As of Oct 24, 2022, 18 and 26 pts were evaluable for response in Arm A and B, respectively. Clinical efficacy was observed in the TN and IP cohorts (Table). The most common treatment-related adverse events (TRAEs) were similar in both cohorts. TRAE of any grade in Arm A were nausea (8, 36%), diarrhea (8, 36%), fatigue (7, 32%), and in Arm B were nausea (10, 34%), fatigue (9, 31%), anorexia (8,27%). Conclusions: The combination of nivolumab, ipilimumab and nintedanib had a manageable toxicity profile and demonstrated promising antitumor activity in both TN and IP aNSCLC patients. Clinical trial information: NCT03377023. TN/Arm A(N=22) IP/ Arm B (N=29) ORR, n,% (95% CI) 9, 40.9 (21.5,63.3) 6, 20.7 (8.7, 40.3) Best overall response, n (%) Complete response (CR), cCR* 1 (4.5), 0 1 (3.4), 1 Partial response (PR), cPR** 8 (36.4), 5 5(17.2), 3 Stable disease (SD) 7 (31.8) 11(37.9) Progressive disease ( PD) 3 (13.6) 9(31.0) Not evaluable /Not assessed 3 (13.6) 3 (10.3) Disease control rate, % (95% CI) 72.7 [49.6,88.4] 58.6 [39.1,75.9] Median PFS, mo (95% CI) 5.5(2.9, N.E.) 2.7 (1.5,6.9) Median OS, mo(95% CI) 17.1 (5.5, N.E) 8.5 (5.7, 25.3) *Confirmed CR, ** Confirmed PR.

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