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

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.

Clinical trial identification

NCT02309177

Legal entity responsible for the study

Ben George, MD

Funding

Celgene Corporation

Disclosure

B. George: Consultant to Celgene Corporation. A. Ko, N. Trunova: Employee of Celgene Corporation. H. Soliman: Advisory role, Celgene. D. Waterhouse: Consultant or advisory role, BMS and Eli Lilly, speakers bureau, BMS, Celgene, Eli Lilly, Genentech/Roche. P. O'Dwyer: consultant: Five Prime Therapeutics; Genentech research funding: BBI Healthcare; Bristol-Myers Squibb; Celgene; Genentech; GlaxoSmithKline; Mirati Therapeutics; Novartis; Pfizer; stock: TetraLogic; expert testimony: Lilly. H. Hochster: consultant: Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Genentech, Amgen, Sirtex Medical, Bristol-Myers Squibb; speakers bureau: Genomic Health. All other authors have declared no conflicts of interest.