Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-PC14586, rezatapopt
PC14586 · 6 trials · 34 indications
Geometric mean metformin peak concentration (Cmax) when administered with rezatapopt versus metformin alone.
Geometric mean rosuvastatin peak concentration (Cmax) when administered with rezatapopt versus rosuvastatin alone.
Geometric mean repaglinide peak concentration (Cmax) when administered with rezatapopt versus repaglinide alone
Geometric mean midazolam peak concentration (Cmax) when administered with rezatapopt versus midazolam alone
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
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
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
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
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of metformin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of rosuvastatin
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of repaglinide
Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of midazolam
Determine the Cmax of PC14586 when co-administered with itraconazole in plasma.
Determine the AUC0-inf of PC14586 when co-administered with itraconazole in plasma.
Determine the Tmax of PC14586 when co-administered with itraconazole in plasma.
Determine the AUC0-24 of PC14586 when co-administered with itraconazole in plasma.
Determine the AUC0-t of PC14586 when co-administered with itraconazole in plasma.
Determine the t1/2 of PC14586 when co-administered with itraconazole in plasma.
Determine the Cmax of PC14586 when co-administered with rabeprazole in plasma.
Determine the AUC0-last of PC14586 when co-administered with rabeprazole in plasma.
Determine the AUC0-inf of PC14586 when co-administered with rabeprazole in plasma.
Determine the Tmax of PC14586 when co-administered with rabeprazole in plasma.
Determine the Cmax of PC14586 when co-administered with famotidine in plasma.
Determine the AUC0-last of PC14586 when co-administered with famotidine in plasma.
Determine the AUC0-inf of PC14586 when co-administered with famotidine in plasma.
Determine the Tmax of PC14586 when co-administered with famotidine in plasma.
Determine Cmax for PC14586 and PC16163 in plasma.
Determine tmax for PC14586 and PC16163 in plasma.
Determine AUC0-inf for PC14586 and PC16163 in plasma.
Determine AUC0-t for PC14586 and PC16163 in plasma.
Determine t 1/2 for PC14586 and PC16163 in plasma.
Determine CL/F for PC14586 and PC16163 in plasma.
Determine Vd/F for PC14586 and PC16163 in plasma.
Determine total radioactivity for PC14586 and PC16163 in whole blood and plasma.
Determine total radioactivity of PC14586 excreted in feces
Determine half life of total radioactivity of PC14586 excreted in feces.
Determine the fraction excreted of total radioactivity of PC14586 in feces.
Determine half-life of fraction excreted of total radioactivity of PC14586 in feces.
Determine total radioactivity of PC14586 excreted in urine.
Determine half life of total radioactivity of PC14586 excreted in urine.
Determine the fraction excreted of total radioactivity of PC14586 in urine.
Determine half-life of fraction excreted of total radioactivity of PC14586 in urine.
Determine the renal clearance of PC14586 in urine.
Number of participants with treatment related adverse events
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Number of participants with treatment related adverse events
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Number of participants with treatment related adverse events
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort
| Arm | Type | Description |
|---|---|---|
| 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. |
| PC14586 and Itraconazole | EXPERIMENTAL | Healthy participants will receive a single, oral dose of PC14586 on day 1. On day 20, participants will receive BID oral doses of itraconazole. On days 21-22, participants will receive a single, oral dose of itraconazole. On day 23, participants will receive a single, oral dose of PC14586 and a single oral dose of itraconazole. On days 24-27, participants will receive a single, oral dose of itraconazole. |
| Part 1: PC14586 and rabeprazole | EXPERIMENTAL | Healthy participants will receive a single, oral dose of PC14586 on day 1. On days 11-13, participants will receive an oral daily dose of rabeprazole. On day 14, participants will receive a co-administration dose of rabeprazole and PC14586. Rabeprazole will be given 1 hour prior to PC14586. Participants will be given a low-fat meal 30 minutes prior to PC14586 dosing. |
| Part 2: PC14586 and famotidine | EXPERIMENTAL | Healthy participants will receive a single, oral dose of PC14586 on day 1. On days 11-13, participants will receive a twice daily, oral dose of famotidine. On day 14, participants will receive PC14586 two hours before a dose of famotidine. Participants will be given a low-fat meal 30 minutes prior to PC14586 dosing. |
| Single, oral dose of [14C]-PC14586 | EXPERIMENTAL | Healthy, male participants will receive a single, oral dose of \[14C\]-PC14586 |
| Part 1 Sequence A | EXPERIMENTAL | Period 1 will be fed, then washout, then Period 2 will be fasted. |
| Part 1 Sequence B | EXPERIMENTAL | Period 1 will be fasted, then washout, then Period 2 will be fed. |
| Part 2 Sequence C | EXPERIMENTAL | Period 1 will be fed, then washout, then Period 2 will be fasted. A different dose of PC14586 will be tested. |
| Part 2 Sequence D | EXPERIMENTAL | Period 1 will be fasted, then washout, then Period 2 will be fed. A different dose of PC14586 will be tested. |
| Part 2 Japanese Cohort | EXPERIMENTAL | 6 Japanese participants will be administered a single dose of PC14586. |
| Phase 1 Monotherapy Dose Escalation | EXPERIMENTAL | Multiple dose levels of daily oral rezatapopt will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of rezatapopt to recommend a Phase 2 dose (RP2D). |
| Phase 1b Combination Therapy Dose Escalation, Part 1 | EXPERIMENTAL | Multiple dose levels of daily oral rezatapopt in combination with a stable dose of pembrolizumab (200 mg IV q3 weeks) will be evaluated in an escalating manner, to determine the maximum tolerated dose and to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of PC14586 to recommend a Phase 2 dose (RP2D) of rezatapopt when administered in combination with pembrolizumab. |
| Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients | EXPERIMENTAL | Additional (expansion of) participants will enroll at the RP2D of daily oral PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 naive patients. |
| Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients | EXPERIMENTAL | Additional (expansion of) participants will enroll at the RP2D of daily oral rezatapopt when administered in combination with pembrolizumab (200 mg IV q3 weeks) for continued evaluation. Participants will have advanced solid tumors harboring a p53 Y220C mutation and are PD(L)-1 relapsed/refractory patients. |
| Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Ovarian Cancer Cohort participants will have locally advanced or metastatic ovarian cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Lung Cancer Cohort participants will have locally advanced or metastatic lung cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Breast Cancer Cohort participants will have locally advanced or metastatic breast cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Endometrial Cancer Cohort participants will have locally advanced or metastatic endometrial cancer harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort | EXPERIMENTAL | Additional (expansion of) participants will dose with 2000 mg daily oral PC14586 (INN: rezatapopt) with food for continued evaluation. Other Solid Tumors Cohort participants will have locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation who meet all eligibility criteria and have measurable disease per RECIST 1.1. |
| Name | Type | Description |
|---|---|---|
| metformin hydrochloride 500 mg tablet | DRUG | 500-mg immediate release tablet PO |
| rosuvastatin 10 mg tablet | DRUG | 10-mg tablet PO |
| repaglinide 0.5 mg tablet | DRUG | 0.5-mg tablet PO |
| midazolam hydrochloride syrup | DRUG | 2 mg dose (5-mg/2.5 mL syrup) PO |
| rezatapopt | DRUG | 2000 mg dose (4 x 500-mg tablets) PO |
| PC14586 | DRUG | First-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation. |
| Itraconazole | DRUG | Antifungal treatment that is a potent inhibitor of CYP3A4. |
| Rabeprazole | DRUG | Part 1: Daily oral dose of rabeprazole on days 11-14. |
| Famotidine | DRUG | Part 2: Twice daily oral dose of famotidine on days 11-13. Single, oral dose of famotidine on day 14. |
| [14C]-PC14586 | DRUG | Single, oral dose of \[14C\]-PC14586 |
| pembrolizumab | DRUG | Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes. |
Inclusion Criteria: 1. Written informed consent 2. 18 years and older 3. ECOG performance status (PS) score of 0 or 1 4. 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 IM...
PC14586 is an investigational small molecule developed by PMV Pharmaceuticals, Inc. (ticker PMVP). It is designed to target the p53 Y220C mutant protein and is in Phase 1 clinical development. The trials listed for PC14586 were conducted in healthy volunteers and have been completed.
PC14586 targets the p53 Y220C mutant protein, a protein target. The drug is a small molecule designed to interact with this specific p53 variant. This mechanism distinguishes it from therapies aimed at other p53 alterations or wild-type p53.
PC14586 is developed by PMV Pharmaceuticals, Inc., which trades under the ticker PMVP. The company is the sponsor of the clinical studies evaluating PC14586, including pharmacokinetic and absorption studies conducted in healthy participants.
PC14586 is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. All four listed trials for PC14586 are Phase 1 studies, and all have been completed.
PC14586 has been studied in four completed Phase 1 trials: NCT06362642, which examined itraconazole effects on pharmacokinetics; NCT06054464, on acid reducing agents; NCT05523687, an absorption, metabolism, and excretion study of [14C]-PC14586; and NCT05249348, on food effects and pharmacokinetics in Japanese volunteers.
Yes, [14C]-PC14586 is an alternative name for PC14586. The [14C] label denotes a carbon-14 radiolabeled form used in an absorption, metabolism, and excretion study, NCT05523687, which was conducted in healthy male participants.