What side effects are associated with this type of intervention?

Common treatments for head and neck cancers, such as concurrent chemoradiation with cisplatin, often result in side effects like anemia, leukopenia, lymphopenia, and mucositis. Severe toxicities can include hypomagnesemia, skin reactions, and sepsis. In the context of targeted therapies like PC14586 (rezatapopt) for TP53 Y220C mutations, side effects may include those typical of targeted agents, such as infusion-related reactions and specific organ toxicities, though detailed side effect profiles for PC14586 are still under investigation.

What prior FDA approvals exist?

FDA-approved treatments for Head and Neck Cancers include a variety of targeted therapies and immunotherapies. Cetuximab, an EGFR inhibitor, has been approved for use in combination with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Pembrolizumab, an anti-PD-1 antibody, is approved for patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Nivolumab, another anti-PD-1 antibody, is also approved for similar indications. While specific FDA approvals for drugs targeting the TP53 Y220C mutation in head and neck cancers are not detailed, these immunotherapies and targeted therapies represent significant advancements in the treatment landscape.

What other types of research exist?

Promising novel alternatives to PC14586 for head and neck cancer patients include: 1) Linifanib (ABT-869) combined with veliparib (ABT-888), which enhances cytotoxicity and induces apoptosis in head and neck carcinoma cells. 2) The combination of ionizing radiation with DNA damage response inhibitors such as CC-115, VE-822, and AZD0156, which induce senescence and apoptosis in head and neck squamous cell carcinoma cells. 3) Wee-1 kinase inhibitor AZD-1775 in combination with cisplatin, which sensitizes high-risk HPV+ head and neck squamous cell carcinoma to apoptosis.

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Small Molecule

PC14586 for Solid Tumors

Phase 1 & 2

Recruiting

Research Sponsored by PMV Pharmaceuticals, Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Advanced solid malignancy with a TP53 Y220C mutation

Must not have

Heart conditions such as unstable angina, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities

Primary CNS tumor (Phase 1, Phase 2 Cohort A)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 12 months per patient (75 months for phase 1 and phase 2)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new oral drug, PC14586 (rezatapopt), alone and with pembrolizumab, in patients with advanced cancers that have a specific genetic mutation. The drug aims to fix a mutated protein to help control cancer growth. The study will determine the best dose and evaluate the drug's safety and effectiveness.

Who is the study for?

Adults with advanced solid tumors that have a specific mutation (TP53 Y220C) can join this trial. They should have tried other cancer treatments without success and be in good physical condition (ECOG 0 or 1). People with certain heart conditions, recent strokes, brain metastases needing steroids, or those on drugs affecting the immune system cannot participate.

What is being tested?

The trial is testing PC14586 alone and combined with pembrolizumab to see how safe and effective they are for treating cancers with the TP53 Y220C mutation. Participants will receive different doses of PC14586 to find out which one works best.

What are the potential side effects?

Possible side effects include reactions at the injection site, fatigue, nausea, skin rash, fever, joint pain from pembrolizumab; plus any additional risks from PC14586 which will be monitored closely due to its newness.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer has worsened despite previous treatments.

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My cancer has a specific TP53 mutation.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have recent severe heart problems or uncontrolled blood pressure.

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My cancer started in the brain or spinal cord.

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I am not taking strong CYP3A4 drugs, QT prolonging medications, or proton pump inhibitors.

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I have had spinal cord compression or cancer spread to the lining of my brain.

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I haven't had cancer treatment in the last 21 days or 5 half-lives before starting the study drug.

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I have had an organ transplant in the past.

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I do not have active, uncontrolled Hepatitis B, C, or HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 12 months per patient (75 months for phase 1 and phase 2)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 12 months per patient (75 months for phase 1 and phase 2)

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 12 months per patient (75 months for phase 1 and phase 2) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt)

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

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

+5 more

Secondary study objectives

Phase 1 Monotherapy (Dose Escalation): Disease Control Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1

Phase 1 Monotherapy (Dose Escalation): Duration of Response per RECIST v1.1 or PCWG3 modified RECIST v1.1

Phase 1 Monotherapy (Dose Escalation): Overall Response Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1

+42 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

9Treatment groups

Experimental Treatment

Group I: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer CohortExperimental Treatment1 Intervention

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.

Group II: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors CohortExperimental Treatment1 Intervention

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.

Group III: Phase 2 Monotherapy Dose Expansion, Lung Cancer CohortExperimental Treatment1 Intervention

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.

Group IV: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer CohortExperimental Treatment1 Intervention

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.

Group V: Phase 2 Monotherapy Dose Expansion, Breast Cancer CohortExperimental Treatment1 Intervention

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.

Group VI: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patientsExperimental Treatment2 Interventions

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 relapsed/refractory patients.

Group VII: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patientsExperimental Treatment2 Interventions

Group VIII: Phase 1b Combination Therapy Dose Escalation, Part 1Experimental Treatment2 Interventions

Multiple dose levels of daily oral PC14586 (INN: 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 PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab.

Group IX: Phase 1 Monotherapy Dose EscalationExperimental Treatment1 Intervention

Multiple dose levels of daily oral PC14586 (INN: 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 PC14586 (INN: rezatapopt) to recommend a Phase 2 dose (RP2D).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

pembrolizumab

2017

Completed Phase 3

~6070

PC14586

2021

Completed Phase 1

~40

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for head and neck cancers include surgery, radiation therapy, chemotherapy, and targeted therapies. Surgery physically removes the tumor, while radiation therapy uses high-energy rays to kill cancer cells. Chemotherapy employs drugs to destroy rapidly dividing cells, and targeted therapies focus on specific molecular targets involved in cancer growth. For instance, PC14586 (rezatapopt) targets the TP53 Y220C mutation, which is crucial because TP53 is a tumor suppressor gene often mutated in cancers. Targeting specific mutations like TP53 Y220C can lead to more effective and personalized treatments, potentially improving outcomes for head and neck cancer patients.

HPV Positive Head and Neck Cancers: Molecular Pathogenesis and Evolving Treatment Strategies.

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Who is running the clinical trial?

Merck Sharp & Dohme LLCIndustry Sponsor

3,996 Previous Clinical Trials

5,181,012 Total Patients Enrolled

PMV Pharmaceuticals, IncLead Sponsor

5 Previous Clinical Trials

111 Total Patients Enrolled

Marc Fellous, MDStudy DirectorVice President of Medical Affairs

Media Library

PC14586 (Small Molecule) Clinical Trial Eligibility Overview. Trial Name: NCT04585750 — Phase 1 & 2

$Cancer Research Study Groups: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort, Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort, Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients, Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort, Phase 1b Combination Therapy Dose Escalation, Part 1, Phase 1 Monotherapy Dose Escalation, Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort, Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients, Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort$