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First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
Trial Status: active
Study STX-478-101 (LY4064809) 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.
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 will provide an adequate tissue sample prior to screening
Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
Is ≥18 years of age at the time of signing the ICF
Has an ECOG performance status score of 0 or 1 at screening
Has adequate organ function as defined per protocol 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 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).
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. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
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
Additional locations may be listed on ClinicalTrials.gov for NCT05768139.
