Home › Breast Cancer › NCT05768139

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

First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

Who can join

Ages 18 and older · All sexes

Key Inclusion Criteria:

* Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
* Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
* Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
* Is ≥18 years of age at the time of signing the ICF
* Has an ECOG performance status score of 0 or 1 at screening
* Has adequate organ function as defined per protocol

Key Exclusion Criteria:

* Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
* Has symptomatic brain or spinal metastases
* Has an established diagnosis of uncontrolled diabetes mellitus (defined as HbA1c ≥8% and/or FBG ≥140 mg/dL \[7.7 mmol/L\] and/or requiring or required insulin).
* Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
* Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
* Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.
* Has had radiotherapy within 14 days before the initiation of study treatment

About the study

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.

What is being tested

• STX-478 (drug)
• Fulvestrant (drug)
• Ribociclib (drug)
• Palbociclib (drug)
• Letrozole (drug)
• Anastrozole (drug)

Sponsor: Eli Lilly and Company · Participants: 880 · Started: Apr 17, 2023

Contact the study team

• Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · Phone: 1-317-615-4559

Official record on ClinicalTrials.gov — NCT05768139

Locations in the U.S.

Conditions

• Breast Cancer
• Cancer (all types)
• Breast Diseases
• Endometrial Cancer
• Ovarian Cancer
• Cervical Cancer
• Head and Neck Cancer
• Head and Neck Squamous Cell Carcinoma
• Hereditary Sensory and Autonomic Neuropathies

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.