Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC).

Abstract

387 Background: This Phase 1 study (NCT01938612) evaluated D (anti-PD-L1 mAb) and T (anti-CTLA-4 mAb) in Asian pts, in whom optimal dosing of D and T is undetermined. No dose-limiting toxicities were observed, and durable responses were seen in a dose escalation phase evaluating various D doses and regimens in Japanese pts (Iguchi, ASCO 2015). The study was subsequently expanded to larger cohorts of Asian pts with advanced solid tumors including BTC. Methods: Two regimens were selected for the expansion phase: D monotherapy (10 mg/kg q2w) and D+T (D 20 mg/kg + T 1.0 mg/kg q4w). One cohort of pts with advanced BTC was enrolled to receive D monotherapy followed by a separate cohort that received D+T with additional pts enrolled if efficacy was observed. Safety, response, and survival endpoints were based on investigator assessment. Results: Pts were enrolled to D (N = 42) or D+T (N = 65). Median age was 64 years for the D cohort and 62 years for the D+T cohort, the majority were male, and ECOG PS was 0 or 1: 64% and 36% for pts in the D cohort and 49% and 51% for pts in the D+T cohort, respectively. Median number of prior chemotherapy regimens was 2 for both cohorts. Treatment-related adverse events (trAE) of any grade occurred in 64% and 82% of pts in the D and D+T cohorts. Grade ≥ 3 trAEs occurred in 19% and 23% of pts in the D and D+T cohorts. trAEs led to discontinuation in 2 pts in the D cohort and 5 pts in the D+T cohort. A death due to trAE (drug-induced liver injury) was reported in the D+T cohort, none in the D cohort. In the D cohort, 2 pts had a partial response (PR) and 7 pts had a PR in the D+T cohort; disease control rate at 12 weeks was 16.7% and 32.2%, respectively. Median duration of response for the D cohort was 9.7 months and 8.5 months for the D+T cohort. Median overall survival was 8.1 (95% CI, 5.6-10.1) months and 10.1 (95% CI, 6.2-11.4) months for the D and D+T cohorts, respectively. Conclusions: Both D monotherapy and D+T combination therapy were tolerable for Asian pts with BTC, and no unexpected toxicities were observed with either regimen. Promising clinical benefit was observed with both D and D+T therapy. This study provides valuable information regarding these therapeutic regimens for future studies in pts with BTC. Clinical trial information: NCT01938612.

New and Emerging Systemic Therapeutic Options for Advanced Cholangiocarcinoma

“…In this phase 1 study preliminary results [108], the disease control rate at 12 weeks was 16.7% and 32.2%, in durvalumab (D) and in durvalumab plus tremelimumab (D + T), respectively. The median duration of response for the durvalumab cohort was 9.7 months and 8.5 months in the durvalumab with tremelimumab cohort.…”

Immune Therapy for Liver Cancers

“…It showed limited ORR (4.7% and 7.7% with monotherapy and combination with tremelimumab, respectively) but promising DCR at 12 weeks (6.7% and 32.2%, respectively), median duration of response (9.7 and 8.5 months, respectively), and median OS (8.1 and 10.1 months, respectively) in pre-treated BTC patients. The grade ≥3 treatment-related adverse events were similar in these two cohorts (19% and 23%, respectively) [96]. Nivolumab was also tested alone or in combination with cisplatin plus gemcitabine in a phase I study in Japanese patients.…”

Systemic therapies for intrahepatic cholangiocarcinoma

“…Table 1 provides a summary of preliminary results from selected completed studies of ICI monotherapy in CCA, with ORRs ranging from 3 to 22%. 82,[84][85][86] Interpretation of these studies is limited by a variety of factors, including singlearm designs with small sample sizes, inconsistent availability of MSI/MMR status and other candidate biomarkers, and heterogeneous or unreported sites of primary tumour, i.e. intrahepatic vs. extrahepatic or gallbladder.…”