First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, as a Single Agent in Patients With Advanced Solid Tumors and in Combination With Endocrine Therapy +/- a CDK4/6 or CDK4 Inhibitor in Patients With Advanced Solid Tumors or Advanced Breast Cancer
Summary
This is an open-label, FIH study designed to evaluate the maximum tolerated dose, recommended Phase 2 dose, safety, tolerability, PK, pharmacodynamics, and preliminary antineoplastic activity of RLY-2608, in advanced solid tumor patients with a Phosphatidylinositol-4,5-bisphosphate-3 kinase, catalytic subunit alpha (PIK3CA) mutation in blood and/or tumor per local assessment. The study will evaluate RLY-2608 as a single agent for patients with unresectable or metastatic solid tumors. It will also evaluate RLY-2608 in combination RLY-2608 + fulvestrant and in triple combination RLY-2608 + fulvestrant + CDK4/6 inhibitor (palbociclib or ribociclib) or CDK4 inhibitor (PF-07220060) for patients with HR+ HER2- locally advanced or metastatic breast cancer. The RLY-2608 single agent arm, RLY-2608 + fulvestrant combination arm, and triple combination arms will have 2 parts: a dose escalation (Part 1) and a dose expansion (Part 2).
Timeline
- Start
- 2021-12-08
- Primary completion
- 2027-04-30
- Completion
- 2027-04-30
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Atirmociclib | Small molecule | 100 mg | Oral |
| Subject | Atirmociclib | Small molecule | 300 mg | Oral |
| Subject | Palbociclib | Small molecule | 125 mg | Oral |
| Subject | RLY-2608 | Small molecule | — | Oral |
| Subject | Ribociclib | Small molecule | 400 mg | Oral |
| Subject | Ribociclib | Small molecule | 600 mg | Oral |
| Background | Fulvestrant | Small molecule | 500 mg | Intramuscular |