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The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy of PC14586 (INN rezatapopt). Overall, 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.
Study details:
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 2 Monotherapy is to evaluate the efficacy of PC14586 (INN: rezatapopt) at the Recommended Phase 2 Dose (RP2D) including the Overall Response Rate (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, pharmacokinetic (PK) properties, quality of life, and other efficacy measures of PC14586 (INN: rezatapopt) at the RP2D.
Enrollment is open for the Phase 2 Monotherapy portion of the study. The primary objective of Phase 1 Monotherapy is to establish the maximum tolerated dose (MTD) and RP2D of PC14586 (INN: rezatapopt). Secondary objectives are to characterize the PK properties, safety and tolerability, and to assess preliminary efficacy including ORR.
Enrollment into Phase 1 Monotherapy is complete. 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.
Enrollment into Phase 1b Combination Therapy is complete.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 12 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-10-29
Primary completion: 2026-03-17
Study completion finish: 2026-07-14
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT04585750
Intervention or treatment
DRUG: PC14586
DRUG: pembrolizumab
Conditions
- • Advanced Solid Tumor
- • Metastatic Cancer
- • Metastatic Solid Tumor
- • Lung Cancer
- • Ovarian Cancer
- • Endometrial Cancer
- • Prostate Cancer
- • Colorectal Cancer
- • Breast Cancer
- • Head and Neck Cancer
- • Advanced Malignant Neoplasm
- • Other Cancer
- • Locally Advanced
Find a site
Closest Location:
Chris O'Brien Lifehouse Hospital
Research sites nearby
Select from list below to view details:
Chris O'Brien Lifehouse Hospital
Camperdown, New South Wales, Australia
Flinders Medical Center
Bedford Park, South Australia, Australia
Monash Medical Centre
Clayton, Victoria, Australia
Linear Clinical Research
Nedlands, Western Australia, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Phase 1 Monotherapy Dose Escalation
| DRUG: PC14586
|
EXPERIMENTAL: Phase 1b Combination Therapy Dose Escalation, Part 1
| DRUG: PC14586
|
EXPERIMENTAL: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 naive patients
| DRUG: PC14586
|
EXPERIMENTAL: Phase 1b Combination Therapy Dose Expansion, PD(L)-1 relapsed/refractory patients
| DRUG: PC14586
|
EXPERIMENTAL: Phase 2 Monotherapy Dose Expansion, Ovarian Cancer Cohort
| DRUG: PC14586
|
EXPERIMENTAL: Phase 2 Monotherapy Dose Expansion, Lung Cancer Cohort
| DRUG: PC14586
|
EXPERIMENTAL: Phase 2 Monotherapy Dose Expansion, Breast Cancer Cohort
| DRUG: PC14586
|
EXPERIMENTAL: Phase 2 Monotherapy Dose Expansion, Endometrial Cancer Cohort
| DRUG: PC14586
|
EXPERIMENTAL: Phase 2 Monotherapy Dose Expansion, Other Solid Tumors Cohort
| DRUG: PC14586
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
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 |
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 |
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 |
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 |
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 |
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 |
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 |
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 outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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) |
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