This study aims to evaluate the effects of rezatapopt on the pharmacokinetics of metformin, rosuvastatin, repaglinide, and midazolam in patients with advanced solid tumors harboring a TP53 Y220C mutation.
Written informed consent
18 years and older
ECOG performance status (PS) score of 0 or 1
Confirmed locally advanced or metastatic solid malignancy with a TP53 Y220C mutation identified through a tumor-tissue based (e.g., FoundationOneCDx, PathGroup, Caris WES, MSK IMPACT, TEMPUS) or a liquid-biopsy based (e.g., Caris, MSK Access) NGS molecular test.
Patients with ovarian, breast, lung, or endometrial tumors who are eligible for the PYNNACLE Phase 2 trial (NCT04585750), unless the corresponding cohort in the PYNNACLE trial is closed to enrollment at the time of screening (to avoid overlap with that study).
Any systemic anticancer therapies, including but not limited to chemotherapy, small molecule, biologic, or hormonal agents from a previous treatment regimen, or investigational anticancer agents from clinical study within 21 days or 5 half-lives (whichever is longer) prior to the first dose of study drugs
Radiotherapy within 14 days of first dose of study drugs. Palliative radiotherapy particularly limited field and stereotactic body radiation therapy to non-target lesions should be allowed.
Inhibitors or inducers of the enzymes and transporters being tested in this study within 14 days of starting study drugs
Sequential
metformin hydrochloride 500 mg tablet
Drug500-mg immediate release tablet PO
rosuvastatin 10 mg tablet
Drug10-mg tablet PO
repaglinide 0.5 mg tablet
Drug0.5-mg tablet PO
midazolam hydrochloride syrup
Drug2 mg dose (5-mg/2.5 mL syrup) PO
rezatapopt
Drug2000 mg dose (4 x 500-mg tablets) PO
Metformin Cmax geometric mean ratio
Geometric mean metformin peak concentration (Cmax) when administered with rezatapopt versus metformin alone.
Rosuvastatin Cmax geometric mean ratio
Geometric mean rosuvastatin peak concentration (Cmax) when administered with rezatapopt versus rosuvastatin alone.
Repaglinide Cmax geometric mean ratio
Geometric mean repaglinide peak concentration (Cmax) when administered with rezatapopt versus repaglinide alone
Midazolam Cmax geometric mean ratio
Geometric mean midazolam peak concentration (Cmax) when administered with rezatapopt versus midazolam alone
Determine the incidence and severity of adverse events to characterize the safety of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam
Number of participants with adverse events, with severity assessed using CTCAE v5.0
Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam
Changes from baseline of physical examinations.
Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam
Changes from baseline of vital signs
Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam
Changes from baseline of clinical laboratory values
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PMV Pharmaceuticals, Inc
Lead sponsor
SCRI Development Innovations, LLC
Collaborator
