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

Part of paid clinical trials in Irvine, California.

Sponsor: PMV Pharmaceuticals, Inc
Study ID: NCT04585750
Phase: PHASE1/PHASE2
Status: Recruiting

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Conditions

Advanced Malignant Neoplasm
Advanced Solid Tumor
Breast Cancer
Colorectal Cancer
ER/PR Positive Breast Cancer
ER/PR(+), Her2(-) Breast Cancer
Endometrial Cancer
Gall Bladder Cancer
HER2+ Breast Cancer
HER2- Breast Cancer
HER2-negative Breast Cancer
HER2-positive Breast Cancer
Head and Neck Cancer
Locally Advanced
Lung Cancer
Metastatic Cancer
Metastatic Solid Tumor
NSCLC
NSCLC (Non-small Cell Lung Cancer)
Non-Small Cell Lung Cancer
Non-Small Cell Lung Carcinoma
Other Cancer
Ovarian Cancer
Prostate Cancer
SCLC
Small Cell Lung Cancer
Small Cell Lung Cancer ( SCLC )
Small Cell Lung Carcinoma
TNBC
Triple Negative Breast Cancer

Eligibility Criteria

Sex: ALL
Age: 12 Years - N/A
Healthy Volunteers: Not accepted

Interventions

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.

Study Details

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.

Key Dates

Start date: Oct 29, 2020
Status verified: Mar 2026
Primary completion: Aug 15, 2026
Completion: Dec 31, 2027

Study Design

Enrollment: 300 participants (estimated)
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Arms

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

Primary Outcome Measure

Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt [ Time Frame: 40 months ]

Central Contacts

PMV Pharma Clinical Study Information Center
(609) 235-4038
[email protected]

Locations (32)

Facility	City	State	ZIP	Site coordinators
University of California Irvine Chao Family Comprehensive Cancer Center	Irvine	California	92868	Zhaohui Arter, MD
University of San Diego Moores Cancer Center	La Jolla	California	92093	Shumei Kato, MD
UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California	90024	Gottfried Konecny, MD
USC Norris Comprehensive Cancer Center	Los Angeles	California	90033	Anthony El-Khoueiry, MD
Rocky Mountain Cancer Center	Denver	Colorado	80218	Allen Cohn, MD
Yale Cancer Center	New Haven	Connecticut	06519	Patricia LoRusso, MD
Medical Oncology Hematology Consultants	Newark	Delaware	19713	Jamal Misleh, MD
University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida	33136	Gilberto de Lima Lopes Jr., MD
Advent Health	Orlando	Florida	32803	Robert Holloway, MD
Florida Cancer Specialists South	Port Charlotte	Florida	33980	Ivor Percent, MD
Dana Farber Cancer Institute	Boston	Massachusetts	02215	Geoffrey Shapiro, MD, PhD
Massachusetts General Hospital	Boston	Massachusetts	02114	Aparna Parikh, MD
Karmanos Cancer Institute	Detroit	Michigan	48201	Dipesh Uprety, MD
Columbia University	New York	New York	10032	June Hou, MD
Memorial Sloan Kettering	New York	New York	10065	Alison Schram, MD
Duke University	Durham	North Carolina	27705	Niharika Mettu, MD, PhD
The Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	44195	Dale Shepard, MD
University of Oklahoma	Oklahoma City	Oklahoma	73104	Debra Richardson, MD
Oregon Health & Science University (OHSU)	Portland	Oregon	97210	Shivaani Kummar, MD
Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	19104	Lainie Martin, MD
University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	15213	Sarah Taylor, MD, PhD
WellSpan York Cancer Center	York	Pennsylvania	17403	Ikechukwu Akunyili, MD
Medical University of South Carolina	Charleston	South Carolina	29425	-
Sarah Cannon Research Institute	Nashville	Tennessee	37203	Melissa Johnson, MD
New Experimental Therapeutics - NEXT Oncology	Austin	Texas	78705	Anthony Tolcher, MD
UT Southwest Simmons Cancer Center	Dallas	Texas	75390	David Miller, MD
UTSW - Moody Outpatient Center - Parkland Health	Dallas	Texas	75235	David Miller, MD
The University of Texas MD Anderson Cancer Center	Houston	Texas	77030	Ecaterina Dumbrava, MD
New Experimental Therapeutics of San Antonio - NEXT Oncology	San Antonio	Texas	78229	Anthony Tolcher, MD
Virginia Cancer Specialists	Fairfax	Virginia	22031	Alexander Spira, MD
University of Washington, Fred Hutchinson Cancer Center	Seattle	Washington	98109	Andrew Coveler, MD
University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	53705	Nataliya Uboha, MD, PhD

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