First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Condition(s) studied

Investigational drug(s) / intervention(s)

STX-478: STX-478 is a mutant-selective PI3Kα inhibitor

Fulvestrant: Fulvestrant

Ribociclib: Ribociclib

Palbociclib: Palbociclib

Letrozole: Letrozole

Anastrozole: Anastrozole

Exemestane: Exemestane

Tamoxifen: Tamoxifen

Abemaciclib: Abemaciclib

Imlunestrant: Imlunestrant

Metformin: Metformin

Study summary

Study STX-478-101 (LY4064809) is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 (LY4064809) in participants with advanced solid tumors with P13Ka mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors. Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with hormone receptor positive (HR+) breast cancer. Part 3 will evaluate STX-478 as combination therapy with endocrine therapy (aromatase inhibitors, fulvestrant, tamoxifen, or imlunestrant) and a CDK4/6 Inhibitor (either Ribociclib, Palbociclib or Abemaciclib) in participants with HR+ breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Eligibility

Primary outcome measure(s)

• Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) — First 28 days of treatment
• Proportion of participants who experience at least 1 DLT during the first 28 days of treatment — First 28 days of treatment
• Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1 — 12 months
• Incidence of TEAEs/SAEs ≥ grade 2 — 12 months
• Frequency of TEAEs according to CTCAE v5.0 criteria — 12 months

Trial sites (65)

+ 25 more sites — see the full list on the official registry below.