A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of PC14586 in Patients With Locally Advanced or Metastatic Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
Status: Recruiting
Location: See all (82) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
SUMMARY
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
Participation Requirements
Sex: All
Minimum Age: 12
Healthy Volunteers: f
View:
• 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
• Adequate organ function
• Measurable disease per RECIST v1.1 (Phase 2)
⁃ Additional Criteria for Inclusion in Phase 1b (rezatapopt) + pembrolizumab combination)
• Anti-PD-1/PD-L1 naive or must have progressed on treatment
• Measurable disease
Locations
United States
California
Hoag Cancer Center
WITHDRAWN
Irvine
University of California Irvine Chao Family Comprehensive Cancer Center
NOT_YET_RECRUITING
Irvine
UCLA Jonsson Comprehensive Cancer Center
RECRUITING
Los Angeles
USC Norris Comprehensive Cancer Center
RECRUITING
Los Angeles
University of San Francisco
WITHDRAWN
San Francisco
Colorado
Rocky Mountain Cancer Center
RECRUITING
Denver
Connecticut
Yale Cancer Center
RECRUITING
New Haven
Delaware
Medical Oncology Hematology Consultants
RECRUITING
Newark
Florida
University of Miami - Sylvester Comprehensive Cancer Center
RECRUITING
Miami
Advent Health
NOT_YET_RECRUITING
Orlando
Florida Cancer Specialists South
RECRUITING
Port Charlotte
Illinois
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
NOT_YET_RECRUITING
Chicago
Indiana
Indiana University
WITHDRAWN
Indianapolis
Massachusetts
Dana Farber Cancer Institute
RECRUITING
Boston
Massachusetts General Hospital
RECRUITING
Boston
Michigan
Karmanos Cancer Institute
RECRUITING
Detroit
North Carolina
Duke University
RECRUITING
Durham
New York
New York University - Long Island Hospital
WITHDRAWN
Mineola
Memorial Sloan Kettering
RECRUITING
New York
New York University Perlmutter Cancer Center
WITHDRAWN
New York
Ohio
The Cleveland Clinic Taussig Cancer Center
RECRUITING
Cleveland
Oklahoma
University of Oklahoma
RECRUITING
Oklahoma City
Oregon
Oregon Health & Science University (OHSU)
RECRUITING
Portland
Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
RECRUITING
Philadelphia
University of Pittsburgh Medical Center
NOT_YET_RECRUITING
Pittsburgh
WellSpan York Cancer Center
NOT_YET_RECRUITING
York
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Tennessee
Sarah Cannon Research Institute
RECRUITING
Nashville
Vanderbilt University Medical Center - Ingram Cancer Center
WITHDRAWN
Nashville
Texas
New Experimental Therapeutics - NEXT Oncology
RECRUITING
Austin
UT Southwest Simmons Cancer Center
NOT_YET_RECRUITING
Dallas
UTSW - Moody Outpatient Center - Parkland Health
NOT_YET_RECRUITING
Dallas
The University of Texas MD Anderson Cancer Center
RECRUITING
Houston
New Experimental Therapeutics of San Antonio - NEXT Oncology
RECRUITING
San Antonio
Virginia
Virginia Cancer Specialists
RECRUITING
Fairfax
Washington
Swedish Medical Center
NOT_YET_RECRUITING
Seattle
University of Washington, Fred Hutchinson Cancer Center
RECRUITING
Seattle
Wisconsin
University of Wisconsin Carbone Cancer Center
RECRUITING
Madison
Other Locations
Australia
Flinders Medical Center
RECRUITING
Bedford Park
Chris O'Brien Lifehouse Hospital
RECRUITING
Camperdown
Monash Medical Centre
RECRUITING
Clayton
Linear Clinical Research
RECRUITING
Nedlands
Mater Cancer Care Centre
RECRUITING
South Brisbane
France
Institut Bergonie
RECRUITING
Bordeaux
Centre Jean Perrin
RECRUITING
Clermont-ferrand
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer
RECRUITING
Lyon
CHU de Nîmes
RECRUITING
Nîmes
EDOG Institut de Cancerologie de l'Ouest
RECRUITING
Saint-herblain
ICANS - Institut de cancérologie Strasbourg Europe
RECRUITING
Strasbourg
Institut Claudius Regaud
RECRUITING
Toulouse
Institute Cancer De Lorraine
RECRUITING
Vandœuvre-lès-nancy
Institut Gustave Roussy
RECRUITING
Villejuif
Germany
Universitätsklinikum Augsburg
RECRUITING
Augsburg
Universitätsklinikum Essen
RECRUITING
Essen
Universitätsklinikum Frankfurt
RECRUITING
Frankfurt Am Main
Asklepios Klinik Altona
RECRUITING
Hamburg
Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg
RECRUITING
Heidelberg
Italy
Fondazione del Piemonte per l'Oncologia (IRCCS)
RECRUITING
Candiolo
ASST Grande Ospedale Metropolitano Niguarda
RECRUITING
Milan
Fondazione IRCCS Istituto Nazionale Dei Tumori
RECRUITING
Milan
Humanitas San Pio X
NOT_YET_RECRUITING
Milan
Istituto Europeo Di Oncologia
RECRUITING
Milan
IRCCS - lstituto Nazionale Tumori - Fondazione G. Pascale
RECRUITING
Napoli
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
RECRUITING
Rome
Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena
RECRUITING
Rome
Istituto Clinico Humanitas
RECRUITING
Rozzano
Republic of Korea
Asan Medical Center
RECRUITING
Seoul
National Cancer Center
NOT_YET_RECRUITING
Seoul
Samsung Medical Center
RECRUITING
Seoul
Seoul University Hospital
RECRUITING
Seoul
Severance Hospital Yonsei University
RECRUITING
Seoul
Singapore
National University Hospital
RECRUITING
Kent Ridge
National Cancer Center of Singapore
RECRUITING
Singapore
Spain
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
RECRUITING
Barcelona
NEXT Oncology-Hospital Quironsalud Barcelona
RECRUITING
Barcelona
Hospital Universitario 12 de Octubre
RECRUITING
Madrid
START MADRID_Hospital Universitario Fundacion Jimenez Diaz
RECRUITING
Madrid
START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
RECRUITING
Madrid
START Rioja
NOT_YET_RECRUITING
Rioja
Hospital Clinico Universitario de Valencia
RECRUITING
Valencia
United Kingdom
Sarah Cannon Research Institute UK
RECRUITING
London
Freeman Hospital
RECRUITING
Newcastle Upon Tyne
Contact Information
Primary
PMV Pharma Clinical Study Information Center
clinicaltrials@pmvpharma.com
(609) 235-4038
Time Frame
Start Date: 2020-10-29
Estimated Completion Date: 2026-07-14
Participants
Target number of participants: 230
Treatments
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 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.
Related Therapeutic Areas
Sponsors
Collaborators: Merck Sharp & Dohme LLC
Leads: PMV Pharmaceuticals, Inc