A phase 1 dose-escalation/expansion clinical trial of mocetinostat in combination with vinorelbine in adolescents and young adults with refractory and/or recurrent rhabdomyosarcoma: Interim results.

11553 Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children. Relapsed/refractory(R/R) RMS has a poor outcome and remains an area of unmet need. Histone deacetylase (HDAC) inhibitors have been shown to have activity in preclinical models of RMS. Mocetinostat (Mirati Pharmaceuticals) is an investigational oral HDAC inhibitor, that targets HDACs 1, 2, 3 and 11. Mocetinostat displayed high activity in in vitro RMS cell lines, RMS xenograft models and exerted synergistic activity in combination with vinorelbine. We report early interim results of the Phase 1 trial of mocetinostat with vinorelbine in R/R RMS. Methods: An investigator initiated Phase 1,open-label, dose escalation/expansion clinical trial. A modified intent to treat approach is used for efficacy analysis for a target accrual of 20 subjects in the dose expansion cohort. Subjects with R/R RMS were age ≥ 18 years old(yo) for the phase 1 dose escalation cohort and ≥12 yo for the phase 1 dose expansion. Mocetinostat 40mg, 70mg or 90mg was taken orally 3 times weekly with vinorelbine 25mg/m 2 IV on day 1,8, and 15 in 21 day cycles. Maximum tolerated dose of mocetinostat in the dose escalation phase was 40mg, which was selected for dose expansion. Subjects were treated until disease progression by RECIST 1.1 or unacceptable toxicity. Results: A total of 8(6 FOXO translocation(+), 1 (FOXO-), and 1 unknown) have been enrolled at time of submission. 5 in dose escalation cohort, and 3 in dose expansion. Median age was 19 yo(range 16-63), Median prior treatment regimens were 2(range 1-4). All patients had measurable metastatic disease. 6 of 8 subjects had prior exposure to vinorelbine in prior salvage chemotherapy or maintenance chemotherapy. As of 20JAN2022 safety cutoff, most common AEs (all grades) observed in 7 evaluable treated patients include neutropenia (n = 5), anemia(n = 5), and nausea(n = 4). The only grade 3 or 4 treatment related AEs were neutropenia, lymphopenia and anemia. Myelosuppression was transient, reversible and responsive to growth factors. No SAEs related to mocetinostat and/or vinorelbine have been reported. As of efficacy cutoff 20JAN2022, 7 of 8 patients are evaluable for response. 4 subjects had a partial response (PR), 2 subjects had stable disease (SD) and 1 subject had progressive disease for a clinical benefit rate of 86% (CR+PR+SD). Rapid responses were seen in the majority of patients at median of 1.5 months(mos). Of the 6 responders, 4 had duration of responses (DOR) > 6 mo with a median DOR of 8 mos (range 4-16mo). Conclusions: In this interim analysis, Mocetinostat plus vinorelbine shows high efficacy and acceptable safety profile in this heavily pretreated group of R/R RMS patients. This study is open to accrual and enrollment is ongoing. Clinical trial information: NCT04299113.