TP53 Y220C MutationPhase 1NCT07372625
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.
A Phase 1 study testing metformin hydrochloride 500 mg tablet, rosuvastatin 10 mg tablet and repaglinide 0.5 mg tablet in people with TP53 Y220C Mutation and Advanced Solid Tumors, run by PMV Pharmaceuticals, Inc at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- TP53 Y220C Mutation, Advanced Solid Tumors
- What is being tested?
- metformin hydrochloride 500 mg tablet, rosuvastatin 10 mg tablet and repaglinide 0.5 mg tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesUnited States
- Study dates
- 4 Feb 2026to Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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
Who cannot join
- 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
Show all 21Show fewer
- 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
- History of prior organ transplant
- Presence of other active invasive cancers other than the one treated in this study within 2 years prior to screening, except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix, or other local tumors considered cured by local treatment
- Known, active, uncontrolled hepatitis B virus infection (i.e., viral load above the limit of quantification), hepatitis C virus infection (i.e., viral load above the limit of quantification), or human immunodeficiency virus infection (viral load >400 copies/mL of blood). Patients whose viral load is controlled should be on established antiretroviral therapy for at least 4 weeks before receiving their first dose of study drugs.
- Patients with a known KRAS single-nucleotide variation (SNV) mutation
- Major surgery (excluding placement of vascular access) within 4 weeks of first dose of study drugs
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
SCRI at Mary Crowley
Dallas, Texas, 75230
Refmal1199studyteam@scri.com
- Recruiting
HealthOne Denver
Denver, Colorado, 80237
Refmal1199studyteam@scri.com
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
Refmal1199studyteam@scri.com
- Recruiting
Florida Cancer Specialists
Orlando, Florida, 32827
Refmal1199studyteam@scri.com
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
Refmal1199studyteam@scri.com
About this study
Official title: A Phase 1, Open-label, 2-part, Drug-Drug Interaction Study to Evaluate the Effects of Multiple Oral Doses of Rezatapopt on the Pharmacokinetics of Metformin, Rosuvastatin, Repaglinide, and Midazolam in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation.
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.
Read the detailed description
Rezatapopt (PC14586) is a first-in-class oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.
This Phase 1, open-label, drug-drug interaction study will investigate the effect of multiple oral doses of rezatapopt on the pharmacokinetics (PK) of metformin, rosuvastatin, repaglinide, and midazolam in patients with advanced solid tumors harboring a TP53 Y220C mutation. This study will consist of 2 parts, Part A and Part B.
Part A is a 24-day drug-drug interaction (DDI) portion that follows a fixed- sequence design, including a screening period and 2 treatment periods.
In Treatment Period 1 patients will receive metformin and rosuvastatin, followed by repaglinide and midazolam. Patients will not receive rezatapopt during Treatment Period 1.
Following washout, in Treatment Period 2 which will begin on Day 6, patients will receive 2000 mg rezatapopt administered orally once daily along with metformin and rosuvastatin, and then repaglinide and midazolam in accordance with the fixed-sequence dosing schedule. Serial PK samples will be collected on designated days throughout Part A.
Patients who complete Part A without suspected disease progression and unacceptable toxicity or another discontinuation criterion and who are deemed likely to continue benefiting from the study treatment, will be allowed to continue treatment with rezatapopt in Part B.
In Part B, patients will receive 2000 mg rezatapopt orally daily in 21-day cycles, up to Cycle 33 (approximately 2 years of rezatapopt treatment, inclusive of Part A) or until another discontinuation criterion is met.
A maximum of approximately 14 patients are planned to enroll in this study.
- Conditions
- TP53 Y220C Mutation, Advanced Solid Tumors
- Being tested
- metformin hydrochloride 500 mg tablet, rosuvastatin 10 mg tablet, repaglinide 0.5 mg tablet, midazolam hydrochloride syrup, rezatapopt
- Keywords
- Y220C, PC14586, PMV Pharma, PMV, rezatapopt, Phase 1, metformin, rosuvastatin, repaglinide, midazolam, DDI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochloride 500 mg tabletDrug
500-mg immediate release tablet PO
rosuvastatin 10 mg tabletDrug
10-mg tablet PO
repaglinide 0.5 mg tabletDrug
0.5-mg tablet PO
midazolam hydrochloride syrupDrug
2 mg dose (5-mg/2.5 mL syrup) PO
rezatapoptDrug
2000 mg dose (4 x 500-mg tablets) PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: metformin hydrochloride 500 mg tablet; Drug: rosuvastatin 10 mg tablet; Drug: repaglinide 0.5 mg tablet; Drug: midazolam hydrochloride syrup; Drug: rezatapopt |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metformin Cmax geometric mean ratio
Geometric mean metformin peak concentration (Cmax) when administered with rezatapopt versus metformin alone.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Number of participants with adverse events, with severity assessed using CTCAE v5.0
Measured: 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
Changes from baseline of physical examinations.
Measured: 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
Changes from baseline of vital signs
Measured: 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
Changes from baseline of clinical laboratory values
Measured: 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
Changes from baseline of 12 lead triplicate ECGs (electrocardiogram)
Measured: 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
Changes in baseline of Eastern Cooperative Oncology Group Performance Status (ECoG) using a scale of 0-5
Measured: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - peak concentration (Cmax)
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt and its metabolites, M13 and M14.
Measured: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - area under the concentration-time curve from pre-dose (time 0) to the time t post-dose (AUC0-t)
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt and its metabolites, M13 and M14.
Measured: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - time of peak concentration (Tmax)
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rezatapopt and its metabolites, M13 and M14.
Measured: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - 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 rezatapopt and its metabolites, M13 and M14.
Measured: Day 6 to Day 24 of Part A
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2026
- Study start4 Feb 2026
- Primary completionMar 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TP53 Y220C MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PMV Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- SCRI Development Innovations, LLC
- Responsible party
- Sponsor
- Investigators
- Deepak Bhamidipati, MD, Study chair, SCRI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07372625
- Sponsor's protocol ID
- PMV-586-106
- Status last verified
- Mar 2026
- First submitted
- 5 Jan 2026
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, 2-part, Drug-Drug Interaction Study to Evaluate the Effects of Multiple Oral Doses of Rezatapopt on the Pharmacokinetics of Metformin, Rosuvastatin, Repaglinide, and Midazolam in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation.
- ClinicalTrials.gov ID
- NCT07372625
- Acronym / sponsor ID
- PMV-586-106
- Conditions
- TP53 Y220C Mutation, Advanced Solid Tumors
- Keywords
- Y220C, PC14586, PMV Pharma, PMV, rezatapopt, Phase 1, metformin, rosuvastatin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- PMV Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Collaborators
- SCRI Development Innovations, LLC
- Study start
- 4 Feb 2026 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 28 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rezatapopt (PC14586) is a first-in-class oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.
This Phase 1, open-label, drug-drug interaction study will investigate the effect of multiple oral doses of rezatapopt on the pharmacokinetics (PK) of metformin, rosuvastatin, repaglinide, and midazolam in patients with advanced solid tumors harboring a TP53 Y220C mutation. This study will consist of 2 parts, Part A and Part B.
Part A is a 24-day drug-drug interaction (DDI) portion that follows a fixed- sequence design, including a screening period and 2 treatment periods.
In Treatment Period 1 patients will receive metformin and rosuvastatin, followed by repaglinide and midazolam. Patients will not receive rezatapopt during Treatment Period 1.
Following washout, in Treatment Period 2 which will begin on Day 6, patients will receive 2000 mg rezatapopt administered orally once daily along with metformin and rosuvastatin, and then repaglinide and midazolam in accordance with the fixed-sequence dosing schedule. Serial PK samples will be collected on designated days throughout Part A.
Patients who complete Part A without suspected disease progression and unacceptable toxicity or another discontinuation criterion and who are deemed likely to continue benefiting from the study treatment, will be allowed to continue treatment with rezatapopt in Part B.
In Part B, patients will receive 2000 mg rezatapopt orally daily in 21-day cycles, up to Cycle 33 (approximately 2 years of rezatapopt treatment, inclusive of Part A) or until another discontinuation criterion is met.
A maximum of approximately 14 patients are planned to enroll in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Part A, Days 1-24 and Part B, Cycles 1-33 | Experimental | Drug: metformin hydrochloride 500 mg tablet, Drug: rosuvastatin 10 mg tablet, Drug: repaglinide 0.5 mg tablet, Drug: midazolam hydrochloride syrup, Drug: rezatapoptPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 castration-resistant prostate cancer must have ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analog or inhibitor or orchiectomy (medical or surgical castration)
Key exclusion criteria (21 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metformin hydrochloride 500 mg tablet500-mg immediate release tablet PO | Drug | Part A, Days 1-24 and Part B, Cycles 1-33 |
| rosuvastatin 10 mg tablet10-mg tablet PO | Drug | Part A, Days 1-24 and Part B, Cycles 1-33 |
| repaglinide 0.5 mg tablet0.5-mg tablet PO | Drug | Part A, Days 1-24 and Part B, Cycles 1-33 |
| midazolam hydrochloride syrup2 mg dose (5-mg/2.5 mL syrup) PO | Drug | Part A, Days 1-24 and Part B, Cycles 1-33 |
| rezatapopt2000 mg dose (4 x 500-mg tablets) PO | Drug | Part A, Days 1-24 and Part B, Cycles 1-33 |
Primary outcome
Metformin Cmax geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
Geometric mean metformin peak concentration (Cmax) when administered with rezatapopt versus metformin alone.
Rosuvastatin Cmax geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
Geometric mean rosuvastatin peak concentration (Cmax) when administered with rezatapopt versus rosuvastatin alone.
Repaglinide Cmax geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
Geometric mean repaglinide peak concentration (Cmax) when administered with rezatapopt versus repaglinide alone
Midazolam Cmax geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
Geometric mean midazolam peak concentration (Cmax) when administered with rezatapopt versus midazolam alone
Metformin AUC0-t geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
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
Rosuvastatin AUC0-t geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
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
Repaglinide AUC0-t geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
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
Midazolam AUC0-t geometric mean ratio
Time frame: Day 1 to Day 24 of Part A
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
PK profile of metformin - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
PK profile of rosuvastatin - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
PK profile of repaglinide - area under the concentration-time curve from pre-dose (time 0) to 24 h post-dose (AUC0-24)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide
PK profile of midazolam - area under the concentration-time curve from pre-dose (time 0) to the time 24 h post-dose (AUC0-24)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam
PK profile of metformin - area under the concentration-time curve from pre-dose (time 0) to 48 h post-dose (AUC0-48)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
PK profile of rosuvastatin - area under the concentration-time curve from pre-dose (time 0) to 48 h post-dose (AUC0-48)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
PK Profile of Metformin - Time of Peak Concentration (Tmax)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
PK Profile of Rosuvastatin - Time of Peak Concentration (Tmax)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
PK Profile of Repaglinide - Time of Peak Concentration (Tmax)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide
PK Profile of Midazolam - Time of Peak Concentration (Tmax)
Time frame: Day 1 to Day 24 of Part A
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam
10 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - peak concentration (Cmax)
Time frame: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - area under the concentration-time curve from pre-dose (time 0) to the time t post-dose (AUC0-t)
Time frame: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - time of peak concentration (Tmax)
Time frame: Day 6 to Day 24 of Part A
PK profile of rezatapopt and its metabolites, M13 and M14 - area under the concentration-time curve from pre-dose (time 0) to the time 24 h post-dose (AUC0-24)
Time frame: Day 6 to Day 24 of Part A
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deepak Bhamidipati, MD study chair
SCRI
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing metformin hydrochloride 500 mg tablet, rosuvastatin 10 mg tablet and repaglinide 0.5 mg tablet in people with TP53 Y220C Mutation and Advanced Solid Tumors, run by PMV Pharmaceuticals, Inc at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact SCRI Medical Support Center (1-615-329-7286, SCRI.InnovationsMedical@scri.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metformin Cmax geometric mean ratio (time frame: Day 1 to Day 24 of Part A). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2026.