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 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

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