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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 144
- 主要终点
- Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
研究概览
简要总结
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.
详细描述
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 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 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 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 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 rezatapopt when administered in combination with pembrolizumab, including ORR. Enrollment into Phase 1b Combination Therapy is complete.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Anti-cancer therapy within 21 days (or 5 half-lives) of receiving the study drug
- •Radiotherapy within 14 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 within 6 months prior to screening, uncontrolled hypertension, a heart attack within 6 months prior to screening, congestive heart failure, prolongation of QT interval, or other rhythm abnormalities
- •Strong CYP3A4 inducers and strong CYP2C9 inhibitors/inducers within 14 days of first dose of rezatapopt
- •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 (rezatapopt monotherapy)
- •Known KRAS mutation, defined as a single nucleotide variant (SNV) (Phase 2)
- •Additional Criteria for Exclusion from Phase 1b (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 rezatapopt
研究组 & 干预措施
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).
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: pembrolizumab (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: pembrolizumab (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: rezatapopt (Drug)
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.
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
时间窗: 40 months
Number of participants with treatment related adverse events
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab
时间窗: The first 28 days of combination treatment arm (starting on Day -7) per patient
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab
时间窗: 18 months
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
时间窗: 12 months for treatment arm
Number of participants with treatment related adverse events
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt
时间窗: 34 months
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
时间窗: 30 months
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)
时间窗: The first 28 days of treatment (Cycle 1) per patient
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
时间窗: 18 months for treatment arm
Number of participants with treatment related adverse events
Phase 1 Monotherapy (Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt
时间窗: 40 months
Number of participants with treatment related adverse events
Phase 1 Monotherapy (Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D)
时间窗: 30 months
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Phase 1 Monotherapy (Dose Escalation): Establish the maximum tolerated dose (MTD) (Phase 1)
时间窗: The first 28 days of treatment (Cycle 1) per patient
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Phase 1b Combination Therapy (Part 1: Dose Escalation): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
时间窗: 18 months for treatment arm
Number of participants with treatment related adverse events
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the maximum tolerated dose (MTD) of rezatapopt when administered in combination with pembrolizumab
时间窗: The first 28 days of combination treatment arm (starting on Day -7) per patient
Incidence of dose limiting toxicities (DLTs) during the first 28 days of treatment with rezatapopt
Phase 1b Combination Therapy (Part 1: Dose Escalation): Establish the Recommended Phase 2 Dose (RP2D) of rezatapopt when administered in combination with pembrolizumab
时间窗: 18 months
RP2D will be determined using available safety and pharmacokinetics and pharmacodynamics data
Phase 1b Combination Therapy (Part 2: Dose Expansion): Determine the number and type of adverse events to characterize the safety of rezatapopt when administered in combination with pembrolizumab
时间窗: 12 months for treatment arm
Number of participants with treatment related adverse events
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt
时间窗: 34 months
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review across all cohorts
Phase 2 Monotherapy (Dose Expansion): Response rate assessment to evaluate the clinical activity / efficacy of rezatapopt in ovarian cancer patients
时间窗: 34 months
Overall response rate in accordance with Response Evaluation Criteria (RECIST) v.1.1 as assessed by independent review in the ovarian cancer cohort
次要结局
- Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)(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(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(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(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(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(41 months for study (end of Phase 1))
- Phase 1 Monotherapy (Dose Escalation): Overall Survival(41 months for study (end of Phase 1))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Peak concentration (Cmax)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Time of peak concentration (Tmax)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)(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(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(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(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(30 months for study (end of Phase 1b))
- Phase 1b Combination Therapy: Overall Survival(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 rezatapopt(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(30 months for study (end of Phase 1b))
- Phase 2 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)(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 rezatapopt(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(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(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(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(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(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(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(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(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(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(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Quality of life assessment(Evaluated at every visit. 34 months for treatment arm (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Overall Response Rate in ovarian cancer cohort per RECIST v1.1 as assessed by Investigator(34 months for study (end of Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 1 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)(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 metabolites when rezatapopt is administered orally.(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(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(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(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(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(41 months for study (end of Phase 1))
- Phase 1 Monotherapy (Dose Escalation): Overall Survival(41 months for study (end of Phase 1))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Peak concentration (Cmax)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Time of peak concentration (Tmax)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: PK profile of rezatapopt in combination with pembrolizumab - Trough observed concentrations (Ctrough/Ctau)(Approximately 12 months per patient (30 months for treatment arm))
- Phase 1b Combination Therapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally in combination with pembrolizumab.(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(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(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(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(30 months for study (end of Phase 1b))
- Phase 1b Combination Therapy: Overall Survival(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 rezatapopt(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(30 months for study (end of Phase 1b))
- Phase 2 Monotherapy: PK profile of rezatapopt - Time of peak concentration (Tmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Peak concentration (Cmax)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve from time zero to time of last sampling timepoint (AUC0-t)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Area under the plasma concentration-time curve in one dosing interval (AUCtau)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: PK profile of rezatapopt - Trough observed concentrations (Ctrough/Ctau)(Approximately 12 months per patient (75 months for Phase 1 and Phase 2))
- Phase 2 Monotherapy: Blood plasma assessment to describe the concentration of rezatapopt and metabolites when rezatapopt is administered orally.(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 rezatapopt(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(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(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(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(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(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(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(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(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(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Overall Survival in ovarian cancer cohort(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Overall Survival across all cohorts(34 months for study (end of Phase 2))
- Phase 2 Monotherapy (Dose Expansion): Quality of life assessment(Evaluated at every visit. 34 months for treatment arm (end of Phase 2))