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

Key Inclusion Criteria:

Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
Has a new or recent tumor biopsy (collected at screening, if feasible) or archival tumor specimen within 12 months prior to screening
Has a tumor that harbors a documented PI3Kα mutation (see the 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, or obtained as part of normal clinical care in a CLIA certified or similarly certified laboratory.
Has at least 1 measurable tumor lesion per RECIST 1.1
Is ≥18 years of age at the time of signing the ICF
Has an ECOG performance status score of 0 or 1 at screening

Key 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
Has symptomatic brain or spinal metastases
Has a tumor with mutations/deletions in PTEN and activating mutations in AKT or mTOR confirmed by a CLIA-certified laboratory
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
Cohorts A0, A1, A2, A3, A4, and B: Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances.
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
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
Has had radiotherapy within 14 days before the initiation of study treatment