Interim safety and clinical activity in patients with advanced NSCLC from a multi-cohort phase 1 study of ramucirumab (R) plus pembrolizumab (P)

Abstract

Background: Hallmarks of tumor growth include angiogenesis and immunosuppression. This is the first study to combine R (VEGFR2 antibody) with P (PD-1 antibody) to target both processes simultaneously. R and P have both shown clinical activity in multiple tumor types. Methods: This ongoing phase 1a/b study (NCT02443324) enrolled pts with gastric or gastroesophageal junction (G/GEJ), NSCLC, urothelial carcinoma (UC), or biliary tract cancer (BTC) following progression on systemic therapy. The primary end point was to define safety and tolerability of adding R to P; preliminary efficacy will be examined. The DAKO PD-L1 22C3 IHC pharmDx assay was used to classify PD-L1 as strong pos (>50%), weak pos (1-49%), or neg for NSCLC pts. Results: As of data cut-off on 23-June-2016, 91 pts have been enrolled with G/GEJ, UC or NSCLC and 66 (73%) experienced a treatment-related AE (TRAE). Fifteen (16%) pts experienced grade 3-4 TRAEs, most commonly colitis (4%) and hypertension (4%). One treatment related death occurred in the G/GEJ cohort (pneumocystis pneumonia and pulmonary sepsis). Pts with previously treated advanced NSCLC (n = 27) received R at 10 mg/kg on Day 1 with P 200 mg on Day 1 q3W. The median age was 65, 78% were male, 96% had a history of smoking, 78% had adenocarcinoma and 15% had squamous-cell carcinoma. Sixteen (59%) pts received >2 and 4 (15%) pts received >3 prior treatment regimens for their disease. Overall, 22 (81%) pts experienced a TRAE, most commonly asthenia (19%) and hypertension (19%). Two (7%) pts experienced grade 3-4 TRAEs (adrenal insufficiency, hyponatremia, delirium, and infusion related reaction). Eight (30%) pts had an objective response (1 unconfirmed). Responses occurred in both histological subtypes and all PD-L1 groups. The disease control rate was 85%. Median time to response was 1.45mo and median duration of response has not been reached. Median PFS has not been reached (95% CI, 3.98 to NR). Median duration of treatment is 6.8mo or longer. Objective responses were still ongoing in all responders. Conclusions: R + P generated no new safety signals and demonstrated promising clinical activity in pts with previously treated advanced NSCLC, including PD-L1 neg pts.