Recruiting

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

ClinicalTrials.gov IDNCT05768139

PhasePHASE1, PHASE2

Enrollment880

SponsorEli Lilly and Company

Age18 Years

SexALL

I'm interested View official listing

Conditions studied

Breast Cancer, Solid Tumors, Adult

About this 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.

Interventions

Drug: STX-478 — STX-478 is a mutant-selective PI3Kα inhibitor
Drug: Fulvestrant — Fulvestrant
Drug: Ribociclib — Ribociclib
Drug: Palbociclib — Palbociclib
Drug: Letrozole — Letrozole
Drug: Anastrozole — Anastrozole
Drug: Exemestane — Exemestane
Drug: Tamoxifen — Tamoxifen
Drug: Abemaciclib — Abemaciclib
Drug: Imlunestrant — Imlunestrant
Drug: Metformin — Metformin

Primary outcomes

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)

Eligibility information

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

Study locations

Ellison Clinic at Saint John's, Los Angeles, California 90064 United States
UCSF Medical Center at Mission Bay, San Francisco, California 94143 United States
University of Colorado Cancer Center, Aurora, Colorado 80045 United States
Yale-New Haven Hospital, New Haven, Connecticut 06510 United States
Florida Cancer Specialists ORLANDO/DDU, Lake Mary, Florida 32746 United States
Moffitt Cancer Center, Tampa, Florida 33612 United States
Winship Cancer Institute, Emory University, Atlanta, Georgia 30322 United States
University of Iowa, Iowa City, Iowa 52242 United States
Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112 United States
Massachusetts General Hospital, Boston, Massachusetts 02115 United States

Showing 10 of 65 reported sites. See the official listing for all locations.

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-10-02.