Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors
by promoting immune priming. The phase 1b/2 JAVELIN Chemotherapy Medley trial evaluated
first-line avelumab + concurrent chemotherapy in patients with advanced urothelial
carcinoma or nonsmall cell lung cancer (NSCLC).Avelumab 800 mg or 1200 mg was administered
continuously every 3 weeks (Q3W) with standard doses of cisplatin + gemcitabine in
patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous
NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase 1b) and confirmed
objective response (phase 1b/2).In phase 1b, urothelial carcinoma and NSCLC cohorts
received avelumab 800 mg (n=13 and n=6, respectively) or 1200 mg (n=6 each) + chemotherapy.
In evaluable patients with urothelial carcinoma treated with avelumab 800 mg or 1200
mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT
occurred in the NSCLC cohort. In phase 2, 35 additional patients with urothelial carcinoma
received avelumab 1200 mg + chemotherapy. Across all treated patients, safety profiles
were similar irrespective of avelumab dose. Objective response rates (95% confidence
internal) with avelumab 800 mg or 1200 mg + chemotherapy, respectively, across phase
1b/2, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0%
(11.8-88.2) and 33.3% (4.3-77.7) in NSCLC.Preliminary efficacy and safety findings
with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with
previous studies of similar combination regimens. Conclusions about clinical activity
are limited by small patient numbers.gov identifier, NCT03317496.
