A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma.

Abstract

349 Background: Hallmarks of tumor growth include immunosuppression and angiogenesis. This is the first study to combine R (anti-VEGFR2) with P (anti-PD-1) to simultaneously target both processes in the urothelial tumor microenvironment. Methods: This ongoing, multi-cohort, phase 1a/b trial (NCT02443324) enrolled patients (pts) with histologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with prior progression on platinum-based systemic therapy, measurable disease, ECOG PS 0-1, and baseline tumor tissue. Eligible pts received R at 10 mg/kg on Day 1 given with P 200 mg on Day 1 q3W. PD-L1 was classified as positive (≥1%) or negative using the DAKO PD-L1 22C3 IHC pharmDx assay. Tumor response was assessed every 6 wks (RECIST v1.1). The primary objective was to assess safety and tolerability of adding R to P and preliminary efficacy will be assessed as a secondary objective. Results: As of 23-June-2016, 24 pts have been treated. The median age was 63 years, 58% were male, 50% had ECOG PS 0, 50% were PD-L1 positive and 67% received study treatment as third or subsequent regimen. Median duration of treatment was 2.14 mo and 2.37 mo for R and P, respectively. All grades treatment-related AEs (TRAE) occurred in 13 (54%) pts; TRAEs occurring in ≥10% of pts were fatigue (21%), nausea (17%), pyrexia (13%), elevated alanine aminotransferase (13%) and elevated aspartate aminotransferase (13%). Three (13%) pts had grade 3 TRAEs (hypertension, colitis, pulmonary embolism; n=1 each). No treatment-related grade 4 or 5 events occurred. Preliminary efficacy data showed two (8%) PD-L1 positive pts had confirmed partial response, 10 (42%) pts had stable disease, and 10 (42%) had progressive disease as their best response. Two (8%) pts were not evaluable for response at the time of analysis. Median duration of response has not been reached (>2.92 mo). Median PFS was 1.87 mo (95% CI, 1.28 to 3.38). Five (21%) pts remain on treatment. Conclusions: R plus P generated no new safety signals and demonstrated antitumor activity in pts with previously treated advanced urothelial carcinoma. Clinical trial information: NCT02443324.