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 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

  1. Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort) 2. Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening 3. Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types) 4. Is ≥18 years of age at the time of signing the ICF 5. Has an ECOG performance status score of 0 or 1 at screening 6. Has adequate organ function as defined per protocol

Exclusion Criteria

  1. Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied 2. Has symptomatic brain or spinal metastases 3. 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). 4. Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances 5. 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. 6. 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. 7. 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

Massachusetts General Hospital
Boston, Massachusetts 02114-2696

More Details

Status
Recruiting
Sponsor
Scorpion Therapeutics, Inc.

Study Contact

For questions concerning enrollment
Please email:
clinical_inquiry_hub@lilly.com