First-in-Human Study of 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 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 and B2, and Part 3 C0, D0, and E0, 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
Experimental
Dose Expansion 		- Cohort A1: HR+/HER2- breast cancer expressing PI3Ka mutations - Cohort A2: Gynecologic cancers - Cohort A3: Head and Neck Squamous Cell Carcinoma - Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, or A3 expressing PI3Kα mutations - Cohort A6: Endometrial cancer
  • Drug: STX-478
    STX-478 is a mutant-selective PI3Kα inhibitor
    Other names:
    • LY4064809
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
  • 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
  • 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

Recruiting Locations

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