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 Genders
- 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) 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
- 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
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Dose Escalation (Advanced Solid Tumors) |
- Cohort A0: Advanced Solid tumors expressing PI3Kα mutations - Cohort A1: HR+ breast cancer expressing PI3Kα mutations |
|
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 |
|
Experimental Dose Selection/Expansion: Combination STX-478 + fulvestrant |
Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations |
|
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 |
|
Recruiting Locations
Boston, Massachusetts 02114-2696
More Details
- Status
- Recruiting
- Sponsor
- Scorpion Therapeutics, Inc.