Abstract CT112: Durvalumab + tremelimumab in patients with metastatic urothelial cancer
Authors: Balar Arjun V. , Mahipal Amit , Grande Enrique , Villalobos Victor M. , Salas Sebastien , Kang Taek Won , Kim Se Hyun , Powles Thomas , Tsai Frank , Naing Aung , Razak Albiruni , Loriot Yohann , Lee Ji Youl , Shin Sang Joon , Morales-Barrera Rafael , Angra Natasha , Xiao Feng , Abdullah Shaad , Heijden Michiel S. Van der 
Published: August 2018

Abstract
Background: PD-L1 blockade with durvalumab (D) is approved as second-line therapy in platinum-refractory metastatic urothelial cancer (mUC). Adding CTLA-4 blockade with tremelimumab (T) may improve responses, particularly in pts with low PD-L1 expression. Here we report safety and efficacy in the mUC cohort of the dose-expansion phase of a phase I, multicenter, open-label study of D+T in pts with advanced solid tumors (NCT02261220).
Methods: Pts with platinum-refractory mUC received D 20 mg/kg + T 1 mg/kg Q4W for 4 months, followed by D 10 mg/kg Q2W for a total of 12 months of treatment. The primary objectives were safety in the mUC cohort and antitumor activity in the subgroup with tumor cell and immune cell PD-L1 expression &lt;25% (assessed by SP263 IHC assay). Secondary objectives included antitumor activity per RECIST v1.1 in other subgroups.
Results: As of Oct 20 2017, 168 pts received treatment and had ≥24 weeks' follow-up. Median age was 65.5 yr (range, 35-85), 78.0% were male, 81.0% had visceral metastases (32.1% liver metastases) and 32.1% had received &gt;1 prior line of chemotherapy. Median duration of follow-up was 11.6 mo. Treatment-related AEs occurred in 75.6% of pts and were Grade 3-4 in 28.6%. One pt died due to a treatment-related AE (pulmonary hemorrhage). Treatment-related AEs led to discontinuation of therapy in 11.9% of pts. Confirmed objective response rate (ORR) was 35/168 (20.8%) including 4 CRs. Responses occurred early (median 1.8 mo) and are durable (median DOR not reached, range 1.9-24.9 mo). At 6 months, the PFS rate was 25.4% and the OS rate was 60.9%. Median PFS was 1.9 mo and median OS was 9.5 mo. Clinical activity was seen regardless of PD-L1 status, but patients with either tumor or immune cell expression ≥25% had numerically higher response rates (29.4% vs 15.1%) and 6-month OS rates than those with &lt;25% expression (Table).
Conclusions: D+T had a manageable safety profile and encouraging antitumor activity and survival rate in previously treated mUC regardless of PD-L1 status.
Response and survivalPD-L1 ≥25% (n=68)PD-L1 &lt;25% (n=86)PD-L1 unknown (n=14)Total (N=168)Confirmed ORR (CR+PR)(95% CI), %29.4 (19.0-41.7)15.1 (8.3-24.5)14.3 (1.8-42.8)20.8 (15.0-27.8)Ongoing ORR, %60.092.310074.3Disease control rate (CR+PR+SD≥24 weeks) (95% CI), %32.4 (21.5-44.8)24.4 (15.8-34.9)42.9 (17.7-71.1)29.2 (22.4-36.7)Median PFS, months (95% CI)3.5 (1.9-3.7)1.8 (1.8-1.9)4.9 (1.8-NE)1.9 (1.8-3.4)PFS 6-month rate, %26.122.638.525.4Median OS, months (95% CI)*18.9 (8.1-NE)8.0 (4.8-10.0)16.4 (7.3-16.4)9.5 (8.1-18.9)OS 6-month rate, %66.451.991.760.9NE, not estimable *Should be interpreted with caution due to limited follow-up at data cutoff Citation Format: Arjun V. Balar, Amit Mahipal, Enrique Grande, Victor M. Villalobos, Sebastien Salas, Taek Won Kang, Se Hyun Kim, Thomas Powles, Frank Tsai, Aung Naing, Albiruni Razak, Yohann Loriot, Ji Youl Lee, Sang Joon Shin, Rafael Morales-Barrera, Natasha Angra, Feng Xiao, Shaad Abdullah, Michiel S. Van der Heijden. Durvalumab + tremelimumab in patients with metastatic urothelial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT112.