Avelumab treatment of metastatic urothelial carcinoma (mUC) in the phase 1b JAVELIN solid Tumor study: Updated analysis with ≥6 months of follow-up in all patients.

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Conference Proceeding

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Annals of Oncology


Background: Avelumab, a human anti-PD-L1 monoclonal antibody, has shown promising efficacy and safety in patients (pts) with mUC. We report an updated analysis of avelumab treatment in 2 cohorts of pts from JAVELIN Solid Tumor (NCT01772004). Methods: Pts with mUC whose disease had progressed after platinum-based therapy or were cisplatin ineligible received avelumab 10 mg/kg Q2W. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Kaplan-Meier (K-M) method was used to estimate DOR, PFS, and OS. Results: As of Sep 2016, 249 pts had received avelumab and were followed for ≤6 mos (median 13.6 mos); 43 pts (17.3%) remained on treatment. 13 pts (5.2%) were cisplatin ineligible, including 7 (2.8%) platinum naïve. Confirmed ORR in all pts (n=249) was 17.3% (95% CI 12.8-22.5; complete response in 4.4%) and the disease control rate was 44.6%. Response was ongoing in 34/43 pts (79.1%), median DOR was 20.1 mos (95% CI 9.7-20.1) and the K-M estimate of DOR of 6mos was 92.7% (95% CI 79.1-97.6). In evaluable pts (n=206), ORR in PD-L1+ and PD-L1- subgroups (≤5% tumor cell cutoff) was 25.6% and 13.7%, respectively. Median PFS was 1.6 mos (95% CI 1.4-2.7), median OS was 8.2 mos (95% CI 6.3-10.8), and the K-M OS rate at 12 mos was 41.9% (95% CI 34.8-48.7). 170/249 pts (68.3%) had a treatment-related adverse event (TRAE) of any grade, most commonly infusion-related reaction (23.3%) and fatigue (17.3%). 26 pts (10.4%) had a grade ≤3 TRAE, most commonly fatigue (1.6%), elevated lipase (1.6%), and pneumonitis (1.2%). 43 pts (17.3%) had an immune-related AE (grade≤3 in 3.6%). 8 pts (3.2%) discontinued avelumab due to a TRAE. There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab showed durable clinical activity and had a manageable and tolerable safety profile in pts with mUC irrespective of PD-L1 expression. A phase 3 trial of avelumab as maintenance therapy after first-line platinum-based therapy for advanced UC is ongoing.



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