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

Open to people ages 18 years and up

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

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 inactivating mutations/deletions in PTEN, activating mutations in AKT (E17K), or a RAS mutation, RAF mutation, or other mutation(s) expected to confer resistance to PI3Kα inhibition, reported by and/or confirmed by a CLIA-certified or similarly certified laboratory; used in a single hospital or institution in EU only
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