Phase I study of nivolumab (nivo) + nab-paclitaxel (nab-P) in solid tumors: results from the pancreatic cancer (PC) and non-small cell lung cancer (NSCLC) cohorts

Abstract

Background: Combining a taxane with an immune checkpoint inhibitor has demonstrated improved response across multiple tumors. Here we present interim results from the PC and NSCLC cohorts of a phase I safety trial of nivo + nab-P in advanced NSCLC (+ carboplatin [C]), advanced PC (± gemcitabine [G]), and metastatic breast cancer. Methods: The primary objective of part 1 is to evaluate dose-limiting toxicities (DLTs). Patients ( pts) treated with ≥ 2 cycles of nivo with chemotherapy (CT) and remained on study for 14 calendar days or who discontinued due to DLT prior to completing 2 cycles of nivo were considered DLT evaluable. If deemed safe, treatment arms will be expanded in Part 2 to further assess safety, tolerability, and antitumor activity. In Arm A Part 1, pts with advanced PC and 1 prior chemotherapy (CT) regimen received nab-P 125 mg/m2 on D 1, 8, and 15 (qw 3/4) + nivo 3 mg/kg on D 1 and 15 of a 28-day cycle. If Arm A is safe, a cohort of CT-naive pts will be enrolled in Arm B and treated with nab-P + G 1000 mg/m2 qw 3/4 + nivo. In Arm C, treatment-naive pts with stage IIIB/IV NSCLC received 4 cycles of nab-P 100 mg/m2 on D 1, 8, and 15 + C AUC 6 on D 1 + nivo 5 mg/kg on D 15 of a 21-day cycle. If Arm C is safe, pts in Arm D will receive the Arm C regimen, except nivo will start at cycle 3. In both NSCLC arms, nivo monotherapy begins at cycle 5. Results: As of Apr 21, 2016, 11 and 20 pts have been treated in Arms A and C. In Arm A, at the time of DLT evaluation (Dec 21, 2015), no DLTs were observed, and no grade 3/4 adverse events (AEs) occurred in > 1 pt. Of the 8 response evaluable pts, 2 achieved a partial response (PR). In Arm C, no DLTs were observed at the time of DLT evaluation (Nov 9, 2015). Of the 14 nivo-treated, response evaluable pts in Arm C, 7 had a PR, and 7 had stable disease. Grade 2 pneumonitis was reported in 1 pt but resolved, and the pt continued on the study. The most common any-grade AEs in either arm were fatigue, nausea, and alopecia. Conclusions: Addition of nivo to nab-P or nab-P/C was tolerable with no DLTs or unexpected AEs in Arms A or C. Efficacy data in Arm C, although preliminary and unconfirmed, is encouraging. Arm B is currently enrolling pts with advanced PC for first-line treatment with nivo + nab-P + G.