A Study of AL58805 in Advanced, Metastatic GYN, STS or Breast Cancers

AL-GB-805 is a global, multicenter, open-label, nonrandomized phase 1b/2a study of oral AL58805, a dual PI3K/mTOR inhibitor, combined with AL8326 (veonetinib), eribulin, or fulvestrant in adults with recurrent, advanced, or metastatic endometrial cancer, cervical cancer, soft tissue sarcoma (STS), or breast cancer for whom at least one prior standard treatment has failed or was not tolerated and no standard effective option remains. Phase 1b uses a standard 3+3 dose-escalation/de-escalation design to select a regimen-specific recommended combination dose (RCD). AL58805 begins at 10 mg and may be increased to 20 mg or reduced to 5 mg based on dose-limiting toxicities (DLTs). Cohort A combines AL58805 with AL8326 40 mg in 28-day cycles; Cohort B combines AL58805 with eribulin 1.4 mg/m² intravenously on Days 1 and 8 of each 21-day cycle; and Cohort C combines AL58805 with fulvestrant 500 mg intramuscularly on Days 1, 15, and 29 and monthly thereafter in 28-day cycles. The RCD is the highest evaluated AL58805 dose at which fewer than 33% of evaluable participants experience a DLT during the first treatment cycle. Phase 2a evaluates each regimen at its RCD. Cohort D includes separate endometrial cancer, cervical cancer, and STS groups receiving AL58805 plus AL8326. Cohort E includes separate STS and breast cancer groups receiving AL58805 plus eribulin. Cohort F includes an HR-positive or other eligible breast cancer group receiving AL58805 plus fulvestrant. Each disease-specific group initially enrolls 17 participants. Under the protocol-specified Simon two-stage design, a group with no objective responses stops for futility; a group with one or more objective responses may enroll 18 additional participants for a total of 35. Tumor response is assessed by the investigator or local radiologist according to RECIST 1.1 at baseline and approximately every 8 weeks beginning on Cycle 3 Day 1. A complete response or partial response is confirmed by repeat imaging 4 to 6 weeks later. Treatment continues until disease progression, unacceptable toxicity, intercurrent illness that prevents safe treatment, withdrawal, sponsor discontinuation, or completion of 12 months of protocol treatment, whichever occurs first. Treatment beyond progression may be allowed when the investigator and sponsor determine that clinical benefit continues and urgent alternative intervention is not being delayed. Participants who remain without progression and continue to benefit may receive study treatment beyond 12 months with investigator and sponsor approval under the protocol continued-access provisions or may later transition to a separate post-trial access protocol. Safety is monitored through the final study visit 4 to 5 weeks after the last study dose, and unresolved related adverse events and serious adverse events are followed until resolution or stabilization. Long-term follow-up includes vital status and subsequent anticancer therapy every 3 to 6 months.