Overview

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 in participants with advanced solid tumors with certain mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors and breast cancer; Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Eligibility

Key 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 archival tumor specimen within 10 years prior to screening
3. Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types) obtained either from tumor or plasma samples, determined by PCR or NGS-based assay as an FDA-approved test in US, CE marked in EU, or obtained as part of normal clinical care in a CLIA certified or similarly certified laboratory.
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

Key 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 a tumor with known mutations/deletions in PTEN and activating mutations in AKT (E17K) confirmed by a CLIA-certified or similarly certified laboratory
4. Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 (based on FPG and HbA1c thresholds defined in the inclusion criteria) requiring antihyperglycemic medication
5. Cohorts A0, A1, A2, A3, A4, A5 and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
6. 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
7. 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
8. Has had radiotherapy within 14 days before the initiation of study treatment