A Study to Investigate the Effects of Multiple Doses of Rezatapopt on the Pharmacokinetics of Metformin, Rosuvastatin, Repaglinide, and Midazolam in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation.

NCT07372625 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PMV-586-106
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

TP53 Y220C Mutation; Advanced Solid Tumors

Keywords

Y220C; PC14586; PMV Pharma; PMV; rezatapopt; Phase 1; metformin; rosuvastatin; repaglinide; midazolam; DDI

Outcome Measures

Primary Outcomes (18)

• Metformin Cmax geometric mean ratio

  Geometric mean metformin peak concentration (Cmax) when administered with rezatapopt versus metformin alone.

  Day 1 to Day 24 of Part A

• Rosuvastatin Cmax geometric mean ratio

  Geometric mean rosuvastatin peak concentration (Cmax) when administered with rezatapopt versus rosuvastatin alone.

  Day 1 to Day 24 of Part A

• Repaglinide Cmax geometric mean ratio

  Geometric mean repaglinide peak concentration (Cmax) when administered with rezatapopt versus repaglinide alone

  Day 1 to Day 24 of Part A

• Midazolam Cmax geometric mean ratio

  Geometric mean midazolam peak concentration (Cmax) when administered with rezatapopt versus midazolam alone

  Day 1 to Day 24 of Part A

• Metformin AUC0-t geometric mean ratio

  Geometric mean metformin area under the concentration-time curve from pre-dose (time 0) to t post-dose (AUC0-t) when administered with rezatapopt versus metformin alone

  Day 1 to Day 24 of Part A

• Rosuvastatin AUC0-t geometric mean ratio

  Geometric mean rosuvastatin area under the concentration-time curve from pre-dose (time 0) to t post-dose (AUC0-t) when administered with rezatapopt versus rosuvastatin alone

  Day 1 to Day 24 of Part A

• Repaglinide AUC0-t geometric mean ratio

  Geometric mean repaglinide area under the concentration-time curve from pre-dose (time 0) to t post-dose (AUC0-t) when administered with rezatapopt versus repaglinide alone

  Day 1 to Day 24 of Part A

• Midazolam AUC0-t geometric mean ratio

  Geometric mean midazolam area under the concentration-time curve from pre-dose (time 0) to t post-dose (AUC0-t) when administered with rezatapopt versus midazolam alone

  Day 1 to Day 24 of Part A

• PK profile of metformin - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin

  Day 1 to Day 24 of Part A

• PK profile of rosuvastatin - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin

  Day 1 to Day 24 of Part A

• PK profile of repaglinide - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide

  Day 1 to Day 24 of Part A

• PK profile of midazolam - area under the concentration-time curve from pre-dose (time 0) to the time 24 h post-dose (AUC0-24)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam

  Day 1 to Day 24 of Part A

• PK profile of metformin - area under the concentration-time curve from pre-dose (time 0) to 48 h post-dose (AUC0-48)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin

  Day 1 to Day 24 of Part A

• PK profile of rosuvastatin - area under the concentration-time curve from pre-dose (time 0) to 48 h post-dose (AUC0-48)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin

  Day 1 to Day 24 of Part A

• PK Profile of Metformin - Time of Peak Concentration (Tmax)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin

  Day 1 to Day 24 of Part A

• PK Profile of Rosuvastatin - Time of Peak Concentration (Tmax)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin

  Day 1 to Day 24 of Part A

• PK Profile of Repaglinide - Time of Peak Concentration (Tmax)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide

  Day 1 to Day 24 of Part A

• PK Profile of Midazolam - Time of Peak Concentration (Tmax)

  Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam

  Day 1 to Day 24 of Part A

Secondary Outcomes (10)

• 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

  From Day 6 to 24 of Part A

• Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam

  Day 6 to 24 of Part A.

• Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam

  Day 6 to Day 24 of Part A

• Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam

  Day 6 to Day 24 of Part A

• Assess the safety and tolerability of multiple doses of rezatapopt alone or co-administered with metformin and rosuvastatin, or repaglinide and midazolam

  Day 6 to Day 24 of Part A

Study Arms (1)

Part A, Days 1-24 and Part B, Cycles 1-33

EXPERIMENTAL

Patients will receive a cocktail of metformin and rosuvastatin after a morning meal on Day 1. Serial PK samples will be collected on Days 1-3. Days 2-5 will serv as a washout period. On Day 2, patients will receive a cocktail of repaglinide and midazolam. Serial PK samples will be collected on Days 2-3. Days 3-5 will serve as a washout period. On Days 6-21 patients will receive rezatapopt with serial PK samples taken on Days 6-7 and sparse PK on Day 14. On Day 22, patients will receive rezatapopt concurrently with a cocktail of metformin and rosuvastatin. Serial PK samples will be collected on Days 22-24. On Day 23, patients will receive rezatapopt concurrently with a cocktail of repaglinide and midazolam. Serial PK samples will be collected on Days 23-24. In Part B, patients will receive rezatapopt as 2000 mg PO QD in 21-day cycles through Cycle 33 (approximately 2 years) or until another discontinuation criterion is met.

Drug: metformin hydrochloride 500 mg tablet; Drug: rosuvastatin 10 mg tablet; Drug: repaglinide 0.5 mg tablet; Drug: midazolam hydrochloride syrup; Drug: rezatapopt

Interventions

metformin hydrochloride 500 mg tablet DRUG

500-mg immediate release tablet PO

Part A, Days 1-24 and Part B, Cycles 1-33

rosuvastatin 10 mg tablet DRUG

10-mg tablet PO

Part A, Days 1-24 and Part B, Cycles 1-33

repaglinide 0.5 mg tablet DRUG

0.5-mg tablet PO

Part A, Days 1-24 and Part B, Cycles 1-33

midazolam hydrochloride syrup DRUG

2 mg dose (5-mg/2.5 mL syrup) PO

Part A, Days 1-24 and Part B, Cycles 1-33

rezatapopt DRUG

2000 mg dose (4 x 500-mg tablets) PO

Part A, Days 1-24 and Part B, Cycles 1-33

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• 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 primary CNS tumors are allowed to enroll
• Patients with castration-resistant prostate cancer must have ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or inhibitor or orchiectomy (medical or surgical castration)
• Adequate organ function
• Life expectancy ≥3 months as assessed by the Investigator

You may not qualify if:

• 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).
• Treatment, food, or drink with any of the following:
• 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
• Sensitive substrates of CYP3A4 or CYP2C8 with a narrow therapeutic index within 14 days of starting study drugs
• Herbal preparations/medications known to be strong or moderate CYP3A4 inhibitors or inducers or to have other significant potential for interaction with rezatapopt within 14 days of starting study drugs
• Foods or drinks with CYP3A inhibition potential (e.g., grapefruit, grapefruit juice, Seville orange juice, pomelos, starfruits) within 14 days of starting study drugs
• Known or suspected significant hypersensitivity, intolerance, or allergy to rezatapopt, metformin, rosuvastatin, repaglinide, or midazolam or any of their excipients or medicinal products with similar chemical structures, food, or other substances
• Previously untreated brain metastases, leptomeningeal metastases, or spinal cord compression due to disease. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 4 weeks prior to starting study drugs, there is no evidence of central nervous system disease progression or mild neurologic symptoms, and there is no requirement for chronic corticosteroid therapy.
• Stroke or transient ischemic attack within 6 months before screening
• Clinically significant, uncontrolled heart diseases currently or within the last 6 months including:
• QTcF \>470 msec obtained as the mean from 3 consecutive resting ECGs. A QTcF value corrected for wide QRS \>120 msec (QTcFBBB) should be used in place of QTcF for patients with non-clinically significant wide QRS \>120 msec due to a pacemaker or bundle branch block.
• Uncontrolled hypertension
• Active gastrointestinal disease that may interfere significantly with the absorption, distribution, metabolism, or excretion of study drug

Sponsors & Collaborators

• PMV Pharmaceuticals, Inc: lead
• SCRI Development Innovations, LLC: collaborator

Study Sites (5)

HealthOne Denver

Denver, Colorado, 80237, United States

RECRUITING

Florida Cancer Specialists

Orlando, Florida, 32827, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

SCRI at Mary Crowley

Dallas, Texas, 75230, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Interventions

Metformin; Tablets; Rosuvastatin Calcium; repaglinide

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Dosage Forms; Pharmaceutical Preparations; Sulfonamides; Amides; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Vivek Subbiah, MD

  SCRI

  STUDY CHAIR

Central Study Contacts

SCRI Medical Support Center

CONTACT

1-615-329-7286; SCRI.InnovationsMedical@scri.com

PMV Pharma Clinical Study Information Center

CONTACT

609-235-4038; clinicaltrials@pmvpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each patient will serve as their own control for assessing the effects of multiple oral doses of rezatapopt on the PK of metformin, rosuvastatin, repaglinide, and midazolam. The study will comprise 2 parts: Part A (24-day DDI portion) will use a fixed-sequence design, comprising a screening period and 2 treatment periods and Part B (Cycle 1 through Cycle 33, rezatapopt only), which will administer rezatapopt in 21-day treatment cycles. In Part A Treatment Period 1, the PK of metformin, rosuvastatin, repaglinide, and midazolam will be evaluated when administered without rezatapopt. In Part A Treatment Period 2, the effects of rezatapopt on the PK of metformin, rosuvastatin, repaglinide, and midazolam will be evaluated. The PK of rezatapopt and its metabolites will also be assessed. Patients who complete Part A without suspected disease progression, unacceptable toxicity or another discontinuation criterion may continue to Part B.

Study Record Dates

• First Submitted: January 5, 2026
• First Posted: January 28, 2026
• Study Start: February 4, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)