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The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

ConditionsAdvanced Solid TumorAdvanced Malignant NeoplasmMetastatic CancerMetastatic Solid TumorLung CancerOvarian CancerEndometrial CancerProstate CancerColorectal CancerBreast CancerOther CancerLocally AdvancedHead and Neck CancerGall Bladder CancerSmall Cell Lung CancerSmall Cell Lung Cancer ( SCLC )Small Cell Lung CarcinomaNSCLCNSCLC (Non-small Cell Lung Cancer)SCLCNon-Small Cell Lung CarcinomaTriple Negative Breast CancerTNBCHER2+ Breast CancerNon-Small Cell Lung CancerER/PR Positive Breast CancerHER2- Breast CancerHER2-positive Breast CancerHER2-negative Breast CancerER/PR(+), Her2(-) Breast Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12+
SponsorPMV Pharmaceuticals, Inc

About this trial

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.

Locally advanced or metastatic solid malignancy with a TP53 Y220C mutation

Eastern Cooperative Oncology Group (ECOG) status of 0 or 1

Previously treated with one or more lines of anticancer therapy and progressive disease

Disqualifiers

Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug

Radiotherapy within 14 days of receiving the study drug

Primary CNS tumor

History of leptomeningeal disease or spinal cord compression

Trial design

Design model

Parallel

Treatments tested in this trial

  • rezatapopt

    Drug

    First-in-class, oral, small molecule p53 reactivator selective for the TP53 Y220C mutation.

  • pembrolizumab

    Drug

    Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Treatment groups

300 Participants
are divided into 9 treatment groups

9

Treatment groups

See each treatment group below.

Group A: Phase 1 Monotherapy Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1b Combination Therapy Dose Escalation, Part 1Experimental treatment 2 interventions
Group C: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patientsExperimental treatment 2 interventions
Group D: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patientsExperimental treatment 2 interventions
Group E: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer CohortExperimental treatment 1 intervention
Group F: Phase 2 Monotherapy Dose Expansion, Lung Cancer CohortExperimental treatment 1 intervention
Group G: Phase 2 Monotherapy Dose Expansion, Breast Cancer CohortExperimental treatment 1 intervention
Group H: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer CohortExperimental treatment 1 intervention
Group I: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors CohortExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt

Number of participants with treatment related adverse events

Time frame
40 months
2

Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)

RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data

Time frame
30 months
3

Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)

Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt

Time frame
The first 28 days of treatment (Cycle 1) per patient
4

Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab

Number of participants with treatment related adverse events

Time frame
18 months for treatment arm

Secondary outcomes

1

Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)

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

Time frame
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
2

Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)

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

Time frame
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
3

Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)

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

Time frame
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
4

Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)

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

Time frame
Approximately 12 months per patient (75 months for Phase 1 and Phase 2)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

PMV Pharmaceuticals, Inc

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

Source ClinicalTrials.gov
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