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

Breast Cancer Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04585750
• Other study ID #: PMV-586-101
• Secondary ID: KEYNOTE-D79MK-34
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 29, 2020
• Est. completion date: July 14, 2026

Study information

• Verified date: February 2024
• Source: PMV Pharmaceuticals, Inc
• Contact: PMV Pharma Clinical Study Information Center
• Phone: (609) 235-4038
• Email: clinicaltrials[@]pmvpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 1/2 study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 (INN: rezatapopt) alone (monotherapy) and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.

Description:

PC14586 (INN: rezatapopt) is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation. The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of PC14586 (INN: rezatapopt). Secondary objectives are to characterize the pharmacokinetic (PK) properties, safety and tolerability, and to assess preliminary efficacy including overall response rate (ORR). The primary objective of Phase 1b Combination Therapy is to establish the MTD/RP2D of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy are to characterize PK, safety and tolerability, and to assess preliminary efficacy of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab, including ORR. The primary objective of Phase 2 Monotherapy is to evaluate the efficacy of PC14586 (INN: rezatapopt) at the RP2D including the ORR in the Ovarian Cancer Cohort and the ORR across all cohorts as determined by blinded independent central review. Secondary objectives of Phase 2 are to characterize the safety, PK properties, quality of life, and other efficacy measures of PC14586 (INN: rezatapopt) at the RP2D.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: July 14, 2026
• Est. primary completion date: March 17, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• At least 18 years of age or 12 to 17 years of age after Safety Review Committee approval.
• Advanced 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 (PC14586 (INN: rezatapopt) + pembrolizumab combination)
• Anti-PD-1/PD-L1 naive or must have progressed on treatment
• Measurable disease

Exclusion Criteria:

• Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
• Radiotherapy within 28 days of receiving the study drug
• Primary CNS tumor
• History of leptomeningeal disease or spinal cord compression
• Brain metastases, unless neurologically stable and do not require steroids to treat associated neurological symptoms
• Stroke or transient ischemic attack within 6 months prior to screening
• 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
• Strong CYP3A4 inhibitors or inducers, medications with a known risk of QT/QTc prolongation, or proton pump inhibitors
• History of gastrointestinal (GI) disease that may interfere with absorption of study drug or patients unable to take oral medication
• History of prior organ transplant
• Known, active malignancy, except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
• Known, active uncontrolled Hepatitis B, Hepatitis C, or human immunodeficiency virus infection Additional Criteria for Exclusion from Phase 2 (PC14586 monotherapy)
• Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2) Additional Criteria for Exclusion from Phase 1b (PC14586 (INN: rezatapopt) + pembrolizumab combination)
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and discontinued from that treatment due to a Grade 3 or higher immune-related AE (irAE)
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention
• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy within 7 days prior to the first dose of study drug
• Hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in past 2 years
• History of radiation pneumonitis
• History of (non-infectious) or active pneumonitis / interstitial lung disease that required steroids
• Active infection requiring systemic therapy
• Known history of HIV infection
• Has previously received PC14586 (INN: rezatapopt)

Related Conditions & MeSH terms

• Advanced Malignant Neoplasm
• Advanced Solid Tumor
• Breast Cancer
• Colorectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Head and Neck Cancer
• Locally Advanced
• Lung Cancer
• Metastatic Cancer
• Metastatic Solid Tumor
• Neoplasms
• Other Cancer
• Ovarian Cancer
• Prostate Cancer

Intervention

Drug:
• PC14586
First-in-class, oral, small molecule p53 reactivator selective for the p53 Y220C mutation.
• pembrolizumab
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion over 30 minutes.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
France	Institut Bergonie	Bordeaux	Gironde
France	Centre Jean Perrin	Clermont-Ferrand	Puy-de-Dôme
France	Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer	Lyon
France	EDOG Institut de Cancerologie de l'Ouest	Saint-Herblain	Loire-Atlantique
France	ICANS - Institut de cancérologie Strasbourg Europe	Strasbourg	Bas-Rhin
France	Institut Claudius Regaud	Toulouse	Haute-Garonne
France	Institut Gustave Roussy	Villejuif	Val-de-Marne
Germany	Universitätsklinikum Augsburg	Augsburg	Bayern
Germany	Universitätsklinikum Essen	Essen	Nordrhein-Westfalen
Germany	Universitätsklinikum Frankfurt	Frankfurt	Hessen
Germany	Asklepios Klinik Altona	Hamburg
Germany	Nationale Centrum für Tumorerkrankungen (NCT) Heidelberg	Heidelberg	Baden-Württemberg
Italy	Fondazione del Piemonte per l'Oncologia (IRCCS)	Candiolo	Torino
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milano	Lombardia
Italy	Fondazione IRCCS Istituto Nazionale Dei Tumori	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome	Lazio
Italy	Istituti Fisioterapici Ospitalieri - Istituto Nazionale Tumori Regina Elena	Rome	Lazio
Italy	Istituto Clinico Humanitas	Rozzano	Lombardia
Korea, Republic of	Asan Medical Center	Seoul
Singapore	National University Hospital	Kent Ridge
Spain	Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON	Barcelona
Spain	NEXT Oncology-Hospital Quironsalud Barcelona	Barcelona
Spain	START MADRID_Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	START MADRID_Hospital Universitario HM Sanchinarro - CIOCC	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	Sarah Cannon Research Institute UK	London	Middlesex
United Kingdom	Royal Victoria Infirmary	Newcastle Upon Tyne	Tyne And Wear
United States	New Experimental Therapeutics - NEXT Oncology	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California, San Diego	La Jolla	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University (OHSU)	Portland	Oregon
United States	New Experimental Therapeutics of San Antonio - NEXT Oncology	San Antonio	Texas
United States	University of Washington, Fred Hutchinson Cancer Center	Seattle	Washington
United States	Florida Cancer Specialists South	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
PMV Pharmaceuticals, Inc	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  France,  Germany,  Italy,  Korea, Republic of,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt)	Number of participants with treatment related adverse events	40 months
Primary	Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)	RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data	30 months
Primary	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 PC14586 (INN: rezatapopt)	The first 28 days of treatment (Cycle 1) per patient
Primary	Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab	Number of participants with treatment related adverse events	18 months for treatment arm
Primary	Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab	Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with PC14586 (INN: rezatapopt)	The first 28 days of combination treatment arm (starting on Day -7) per patient
Primary	Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab	RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data	18 months
Primary	Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt) when administered in combination with pembrolizumab	Number of participants with treatment related adverse events	12 months for treatment arm
Primary	Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of PC14586 (INN: rezatapopt)	Overall response rate in accordance with Response Evaluation Criteria across all cohorts (RECIST) v.1.1 as assessed by independent review	34 months
Secondary	Phase 1 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Peak concentration (Cmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Time of peak concentration (Tmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy: PK profile of PC14586 (INN: 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy: PK profile of PC14586 (INN: 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Trough observed concentrations (Ctrough/Ctau)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy: Blood plasma assessment to describe the concentration of PC14586 and metabolite (M1) when PC14586 (INN: rezatapopt) is administered orally.	Blood plasma concentration	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 1 Monotherapy (Dose Escalation): Overall Response Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1 Monotherapy (Dose Escalation): Time to Response per RECIST v1.1 or PCWG3 modified RECIST v1.1	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1 Monotherapy (Dose Escalation): Duration of Response per RECIST v1.1 or PCWG3 modified RECIST v1.1	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1 Monotherapy (Dose Escalation): Disease Control Rate per RECIST v1.1 or PCWG3 modified RECIST v1.1	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1 Monotherapy (Dose Escalation): Progression Free Survival per RECIST v1.1 or PCWG3 modified RECIST v1.1	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1 Monotherapy (Dose Escalation): Overall Survival	Evaluation of preliminary anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	41 months for study (end of Phase 1)
Secondary	Phase 1b Combination Therapy: PK profile of PC14586 (INN: rezatapopt) in combination with pembrolizumab - Peak concentration (Cmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: PK profile of PC14586 (INN: rezatapopt) in combination with pembrolizumab - Time of peak concentration (Tmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: PK profile of PC14586 (INN: rezatapopt) in combination with pembrolizumab - 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: PK profile of PC14586 (INN: rezatapopt) in combination with pembrolizumab - 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: PK profile of PC14586 (INN: rezatapopt) in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: Blood plasma assessment to describe the concentration of PC14586 (INN: rezatapopt) and metabolite (M1) when PC14586 (INN: rezatapopt) is administered orally in combination with pembrolizumab.	Blood plasma concentration	Approximately 12 months per patient (30 months for treatment arm)
Secondary	Phase 1b Combination Therapy: Overall Response Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Time to Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Duration of Response per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Disease Control Rate per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Overall Survival	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt)	Number of participants with treatment related adverse events	30 months for study (end of Phase 1b)
Secondary	Phase 1b Combination Therapy: Progression Free Survival per RECIST v1.1, iRECIST, or PCWG3 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) in combination with pembrolizumab	30 months for study (end of Phase 1b)
Secondary	Phase 2 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Time of peak concentration (Tmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Peak concentration (Cmax)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy: PK profile of PC14586 (INN: 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy: PK profile of PC14586 (INN: 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 PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy: PK profile of PC14586 (INN: rezatapopt) - Trough observed concentrations (Ctrough/Ctau)	Pharmacokinetic parameters will be determined by non-compartmental methods using pharmacokinetic profile of PC14586 (INN: rezatapopt)	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy: Blood plasma assessment to describe the concentration of PC14586 (INN: rezatapopt) and metabolite (M1) when PC14586 (INN: rezatapopt) is administered orally.	Blood plasma concentration	Approximately 12 months per patient (75 months for Phase 1 and Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Determine the number and type of adverse events to characterize the safety of PC14586 (INN: rezatapopt)	Number of participants with treatment related adverse events	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Overall Response Rate across all cohorts per RECIST v1.1 as assessed by Investigator	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Overall Response Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Time to Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Time to Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Duration of Response in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Duration of Response across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Disease Control Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Disease Control Rate across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Progression Free Survival in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Progression Free Survival across all cohorts per RECIST v1.1 as assessed by Investigator and as assessed by independent review	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts	Evaluation of anti-tumor activity of PC14586 (INN: rezatapopt) as a single agent	34 months for study (end of Phase 2)
Secondary	Phase 2 Monotherapy (Dose Expansion): Quality of life assessment	Changes from baseline in quality of life as measured by a validated instrument, for participants 18 and older	Evaluated at every visit. 34 months for treatment arm (end of Phase 2)