Abstract 555P
Background
Anti-PD1/PD-L1 agents have only moderate antitumour activity in some AST, including breast (BC), prostate (PC), cervical (CC) and head and neck (HNC) cancers. Combining anti-PD-L1 with anti-CTLA therapies (such as D and T, respectively) may significantly improve efficacy. Metronomic chemotherapy may have pro-immune properties. MOVIE is an ongoing multi-cohort phase 1/2 study examining the combination of T+D with MOV in various AST.
Methods
Patients (pts) with BC, CC, HNC, PC and miscellaneous cancers with high tumour mutational burden (hTMB) were eligible in case of advanced disease resistant to conventional therapies. T was administered IV, 75 mg Q4W, for up to 4 cycles and D was administered IV, 1500 mg Q4W, for up to 26 cycles (or 24 months whichever is longer). MOV was administered orally thrice weekly until disease progression and up to 3 dose levels (DL) were to be investigated (DL1=30 mg, DL2=40 mg and DL-1=20 mg). The primary objective of the phase 1 part of the study was to determine the maximum tolerated dose (MTD) and the recommended dose for phase II (RP2D) of MOV in combination with T+D. The study used a 3+3 dose escalation design and primary endpoint was the occurrence of Dose Limiting Toxicities (DLTs) on cycle 1. Secondary objectives included safety, clinical benefit rate, overall response rate, duration of response and progression-free survival.
Results
In total, 14 pts (13 female and 1 male) were enrolled in the phase I part of the study, this incuded BC (n=9), CC (n=2), hTMB (n=2) and PC (n=1). The median age was 53 (range 32-79). Twelve pts were evaluable for the dose escalation part. No DLT was observed in the first 3 pts treated and they were evaluable at DL1 and DL2. An extension cohort of 6 pts was included at DL2 in order to confirm the RP2D and 1 DLT was observed (neutropenia with fever, grade 4). Accordingly, DL2 was selected as the RP2D. Two (14.3%), 4 (28.6%) and 4 (28.6%) pts had grade (G) 3 or higher adverse events (AEs) related to MOV, D and T, respectively. Immune-related AEs included colitis (1G2, 1G3), rash (2G1, 1G3), and thyroiditis (2G1, 3G2). No toxic deaths were recorded. One pt (CC) had a complete response. Phase II is ongoing with promising results in BC and CC cohorts.
Conclusions
MOV 40 mg thrice weekly is the RP2D in combination with T+D. The safety profile of the combination is consistent with previous reports of T+D combination or MOV.
Clinical trial identification
NCT03518606.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
AstraZenca, Pierre Fabre.
Disclosure
All authors have declared no conflicts of interest.