Abstract 343P
Background
Anti-PD1/PD-L1 agents have limited activity in pre-treated ABC. Combining anti-PD-L1 with anti-CTLA-4 (such as D and T, respectively) may improve antitumor activity. Metronomic chemotherapy a continuous administration of a cytotoxic agent but at a lower dose has activity in ABC and may have pro-immune properties. MOVIE is an ongoing, multi-cohort phase I/II study examining the combination of T+D with MOV in advanced solid tumors.
Methods
Patients (pts) were eligible in case of ABC 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 at 40 mg orally thrice weekly, until disease progression. Primary endpoint of phase II part was clinical benefit rate (CBR= CR, PR or SD ≥ 24 weeks) according to RECIST 1.1. Continuous monitoring of efficacy was planned using a Bayesian approach, with interim analyses (IA) on the first 10 pts and then every 5 pts. Secondary objectives included safety, ORR, DOR and PFS.
Results
16 pts with ABC were analyzed for the first IA. Median age was 49 (range, 32-70), PS-OMS was 0 (9, 56%) or 1 (7, 44%). Median number of previous metastatic lines of systemic treatment was 3 (0 to 7). As of Jan. 2020, 2 pts were on treatment, 12 stopped for disease progression and 2 for unacceptable toxicity; median follow-up was 5.4 mo (2.4 - 10.1). Clinical benefit was observed for 4 pts: 3 PR with durations of 15.4, 15.4 and 24.4 wks. and 1 SD ≥ 24 wks. Bayesian estimations of the mean CBR (95%(CI)) according to the prior distributions defined are reported in the table. 11 (69%) pts had grade ≥2 treatment-related adverse events (TRAE), including 6 pts (38%) with grade ≥3. Immune-related AE included colitis (1 G2, 2 G3), thyroiditis (8 G2). No toxic death was recorded. Table: 343P
Bayesian estimations of the mean CBR
| - Prior non-informative beta (1, 1) : 27.8% [10.3%; 49.9%] |
| - Informative Prior Beta (1.8, 4.2) : 26.4% [10.6%; 46.1%] |
| - Less informative optimism Beta (0.75, 1.75) : 25.7% [9.1%; 47.2%] |
Conclusions
T+D+MOV has promising activity in pretreated ABC. Toxicity profile was consistent with previous reports of T+D combination or MOV.
Clinical trial identification
NCT03518606.
Legal entity responsible for the study
UNICANCER.
Funding
AstraZeneca, Pierre Fabre.
Disclosure
All authors have declared no conflicts of interest.