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

Purpose

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.

Conditions

  • Breast Cancer
  • Solid Tumors, Adult

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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 Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Masking Description
In Part 1, Part 2 B0, B2, and B3, and Part 3 C0, D0, E0, F and A8, participants are assigned to intervention. In Part 2 B1 and Part 3 C1, D1, and E1, participants are randomized to doses

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Dose Escalation (Advanced Solid Tumors) 		- Cohort A0: Advanced Solid tumors expressing PI3Kα mutations - Cohort A1: HR+ breast cancer expressing PI3Kα mutations
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
    • Tersolisib
Experimental
Dose Expansion 		- Cohort A2: Gynecologic cancers - Cohort A3: Head and Neck Squamous Cell Carcinoma - Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, A3 expressing PI3Kα mutations - Cohort A6: Endometrial cancer - Cohort A7: Non-gastrointestinal solid tumors
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
    • Tersolisib
Experimental
Dose Selection/Expansion: Combination STX-478 + fulvestrant 		Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
    • Tersolisib
  • Drug: Fulvestrant
    Fulvestrant
    Other names:
    • Faslodex
Experimental
Dose Selection/Expansion Combination 		STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
    • Tersolisib
  • Drug: Fulvestrant
    Fulvestrant
    Other names:
    • Faslodex
  • Drug: Ribociclib
    Ribociclib
    Other names:
    • Kisqali
  • Drug: Palbociclib
    Palbociclib
    Other names:
    • Ibrance
  • Drug: Letrozole
    Letrozole
    Other names:
    • Femara
  • Drug: Anastrozole
    Anastrozole
    Other names:
    • Arimidex
  • Drug: Exemestane
    Exemestane
    Other names:
    • Aromasin
  • Drug: Tamoxifen
    Tamoxifen
    Other names:
    • Nolvadex
    • Soltamox
  • Drug: Abemaciclib
    Abemaciclib
    Other names:
    • Verzenio
  • Drug: Imlunestrant
    Imlunestrant
    Other names:
    • Inluriyo
Experimental
Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant] 		CDK4/6 inhibitor therapy in Cohort A8: all solid tumors Cohort B2 and Cohort F: HR+/HER2- or HR+/HER2 low breast cancer expressing PI3Kα mutations
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
    • Tersolisib
  • Drug: Fulvestrant
    Fulvestrant
    Other names:
    • Faslodex
  • Drug: Ribociclib
    Ribociclib
    Other names:
    • Kisqali
  • Drug: Palbociclib
    Palbociclib
    Other names:
    • Ibrance
  • Drug: Letrozole
    Letrozole
    Other names:
    • Femara
  • Drug: Anastrozole
    Anastrozole
    Other names:
    • Arimidex
  • Drug: Exemestane
    Exemestane
    Other names:
    • Aromasin
  • Drug: Abemaciclib
    Abemaciclib
    Other names:
    • Verzenio
  • Drug: Metformin
    Metformin

Recruiting Locations

Ellison Clinic at Saint John's
Los Angeles, California 90064

UCSF Medical Center at Mission Bay
San Francisco, California 94143

University of Colorado Cancer Center
Aurora, Colorado 80045

Moffitt Cancer Center
Tampa, Florida 33612

Winship Cancer Institute, Emory University
Atlanta, Georgia 30322

University of Iowa
Iowa City, Iowa 52242

Louisiana State University Health Sciences Center
New Orleans, Louisiana 70112

Massachusetts General Hospital
Boston, Massachusetts 02115

Dana-Farber Cancer Institute
Boston, Massachusetts 02215

START Midwest
Grand Rapids, Michigan 49546

Saint Luke's Cancer Institute
Kansas City, Missouri 64111-3220

Washington University
St Louis, Missouri 63110

Memorial Sloan Kettering Cancer Center
New York, New York 10065

UH Cleveland Medical Center
Cleveland, Ohio 44106

Stefanie Spielman Comprehensive Breast Center
Columbus, Ohio 43212

Providence Cancer Institute Franz Clinic
Portland, Oregon 97213

The West Clinic, PLLC dba West Cancer Center
Germantown, Tennessee 38138

Sarah Cannon Research Institute
Nashville, Tennessee 37203

Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas 75246-2092

University of Texas Southwestern
Dallas, Texas 75390

University of Texas MD Anderson Cancer Center
Houston, Texas 77030

START San Antonio
San Antonio, Texas 78229

START Mountain Region
West Valley City, Utah 84119

USO-Virginia Cancer Specialists, PC
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
LillyTrials@Lilly.com