First-in-Human Study of STX-478, a Mutant-Selective PI3Kalpha Inhibitor as Monotherapy and in Combination with Other Antineoplastic Agents in Participants with Advanced Solid Tumors

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Ira
Winer, MD, PhD, FACOG
Oncology - Gynecologic, Oncology - Surgical View Profile

Primary Objectives:

To determine the OBD and MTD of STX-478
administered as monotherapy in participants with
breast cancer expressing PI3Kα H1047X mutations
or other kinase domain mutations

Secondary Objectives:

To characterize the overall safety and tolerability of
STX-478 administered as monotherapy in
participants with breast cancer expressing PI3Kα
H1047X mutations or other kinase domain mutations
To evaluate the effect of STX-478 administered as
monotherapy on the glucose metabolism of
participants with breast cancer expressing PI3Kα
H1047X mutations or other kinase domain mutations
To characterize the PK profile of STX-478
To evaluate the preliminary antitumor activity of
increasing dose levels of STX-478 administered as
monotherapy in participants with breast cancer
expressing PI3Kα H1047X mutations or other kinase
domain mutations
To evaluate the effect of STX-478 on quality of life

Eligibility

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 10 years prior to screening
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.
Is ≥18 years of age at the time of signing the ICF
Has an ECOG performance status score of 0 or 1 at screening

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 known mutations/deletions in PTEN and activating mutations in AKT (E17K) confirmed by a CLIA-certified or similarly 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, A5 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

Locations

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices