Ongoing first-line randomized phase II–III trials with ICI for advanced BTCs

Study name/numberPhaseEstimated sample sizeExperimental treatmentComparatorPrimary endpointSecondary endpoints
II150 patientsAtezolizumab plus bevacizumab plus CisGem1Atezolizumab plus placebo plus CisGem1PFS per RECIST v1.1 by the investigatorOS, ORR, DOR, DCR per RECIST v1.1 by investigator, TTCD, safety, ADAs for atezolizumab
NCT04066491II–III512 patientBintrafusp alfa (M7824) plus CisGem1Placebo plus CisGem1Safety run-in part: DLTs Double-blinded part: OSORR, DOR, PFS per RECIST v1.1 by investigator, safety, Bintrafusp alfa PK, ADAs for Bintrafusp alfa
III757 patientsDurvalumab plus CisGem1Placebo plus CisGem1OSPFS, ORR, DOR per RECIST v1.1 by ICR and by investigator, OS by PD-L1 expression, PK of durvalumab, ADAs for durvalumab, QoL
III1048 patientsPembrolizumab plus CisGem1Placebo plus CisGem1OSORR, DOR, PFS per RECIST v1.1 by ICR, safety
NCT03478488III480 patientsKN035 plus GEMOX2GEMOX2OSPFS, ORR, DCR, DOR, TTP per RECIST v1.1 by ICR

CisGem: cisplatin 25 mg/mq + gemcitabine 1000 mg/mq intravenously (i.v.) on day 1 and 8 on a 21-day cycle up to 8 cycles; 2GEMOX: gemcitabine 1000 mg/mq on day 1 and 8 and oxaliplatin 85 mg/mq i.v. on day 1 of a 21-day cycle up to 6 cycles. TTCD: time to clinical deterioration; ADAs: anti-drug antibodies; DLTs: dose-limiting toxicities; PK: pharmacokinetics; TTP: time to progression