TulmiSTAR-02: A Two-part Phase I Dose Escalation Study of Tulmimetostat (DZR123) in Combination With Darolutamide or Abiraterone Followed by Open-label, Randomized, Phase II Dose Expansion Study to Assess the Safety and Efficacy of Tulmimetostat in Combination With Darolutamide Versus Darolutamide Alone in Patients With Metastatic Hormone-sensitive Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 181
- 试验地点
- 34
- 主要终点
- Phase I (Group A and Group B): Dose-limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and efficacy of two different treatment combinations of tulmimetostat in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). Phase I aims to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in combination with darolutamide or abiraterone. Phase II is designed to further evaluate the efficacy and safety of tulmimetostat in combination with darolutamide compared with darolutamide alone in participants with mHSPC.
详细描述
This is a Phase I/II, open-label, global, multicenter study evaluating tulmimetostat in combination with androgen receptor pathway inhibitors in participants with de novo or recurrent metastatic hormone-sensitive prostate cancer (mHSPC). The study consists of two phases:
Phase I (Dose Escalation)
Phase I includes two treatment groups:
- Group A (Part 1): tulmimetostat in combination with darolutamide.
- Group B (Part 2): tulmimetostat in combination with abiraterone.
The primary objective of Phase I is to determine the recommended dose(s) for expansion (RDE) of tulmimetostat in each combination regimen through a parallel dose-escalation design guided by a Bayesian Logistic Regression Model (BLRM). Enrollment will follow a staggered approach between the two groups. Participants may have received prior taxane-based chemotherapy and/or prior androgen receptor pathway inhibitor (ARPI) therapy and must not have received prior radioligand therapy. Participants will continue androgen deprivation therapy (ADT) to maintain castrate testosterone levels (<50 ng/dL or <1.7 nmol/L) according to investigator choice and local prescribing information. In Group B, abiraterone will be administered with prednisone or prednisolone according to local prescribing information.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both.
- Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Adequate bone marrow and organ function
- Prior ADT: Participants must have started ADT at least 1 month (at least 28 days) but no more than 12 months before study entry and be willing to continue ADT during treatment
- Prior taxane use for mHSPC is permitted:
- Phase I and II: Participants may have received, but not progressed on, one prior taxane-based therapy.
- Phase II: Limited to 25% participants with prior taxane use.
- Prior ARPI is allowed in both Phase I and Phase II:
- Prior ARPI use in biochemical recurrence (BCR) or curative treatment is allowed for any duration, provided therapy was discontinued and participant had no evidence of conventional imaging positive metastatic disease at that time
- Prior ARPI use in mHSPC is permitted but not mandated. If participants meet all study eligibility criteria, they are required to stop their prior ARPI after providing informed consent and remain off ARPI until Cycle 1 Day 1, when study treatment is initiated.
- Phase I: Allowed for any duration.
- Phase II: Allowed prior exposure to ARPI is ≤4 months. Participants with ongoing use of darolutamide are not eligible.
- Participants with ongoing ARPI are eligible for a switch from their ongoing ARPI therapy if they have not progressed to CRPC disease, and meet any of the criteria, indicative of suboptimal biochemical response, or intolerability, as assessed by the Investigator:
- Evidence of insufficient PSA control or suboptimal PSA response, defined as PSA ≥ 0.2 ng/mL after 6-12 months ADT and no more than 4 months of current ARPI therapy in mHSPC with declining or stable PSA trend. Eligibility based on biochemical progression should be supported by objective evidence (e.g. PSA results).
- Intolerance and non-compliance: Participant's inability to tolerate or comply with the prescribed ARPI. The site should maintain documentation to support the appropriateness of therapy changes resulting from intolerance or non-compliance.
- Other permitted prior local therapy for mHSPC:
- Phase I and II: Prior prostate-directed radiation or surgical intervention. Radiation must be completed before study entry; surgery at least 2 weeks prior.
- Key
排除标准
- Participants with evidence of mCRPC or biochemical recurrence / PSA only disease or asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy and with normal PSA for ≥ 1 year prior to the start of study treatment.
- Participants who have not received ARPI treatment for mHSPC and present with PSA levels of ≤0.5 ng/mL or those with prior/ongoing ARPI treatment presenting with PSA levels of ≤ 0.2 ng/mL prior to treatment assignment/randomization.
- Participants with CNS metastases are excluded unless:
- they have received prior therapy (e.g. surgery, radiotherapy, gamma knife), are neurologically stable and asymptomatic.
- they are not receiving corticosteroid for the purpose of maintaining neurologic integrity and have baseline and subsequent radiological imaging of the brain.
- Concurrent use of first-generation anti-androgens (like bicalutamide). Prior use of a first-generation anti-androgen drug in the context of ADT initiation with a GNRH analog is allowed, provided it was administered for ≤14 days and the last dose was administered ≥7 days from the study entry.
- Systemic ketoconazole is used as antineoplastic treatment for prostate cancer.
- Previous exposure to radioligand therapy.
- Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
- Previous treatment with any Polycomb Repressive Complex 2 (PRC2) inhibitor, including but not limited to Enhancer of Zeste Homolog 2 (EZH2) inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
- Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study.
- Participants taking prohibited medication(s) (e.g., strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors that cannot be stopped within 7 days or 5 half-lives (whichever is longer) prior to study treatment and for the duration of the study treatment or prohibited herbal product(s) that cannot be stopped 7 days prior to study treatment.
- Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Participants with a history of leukemia/lymphoma and/or MDS are not eligible.
- Other inclusion/exclusion criteria may apply
研究组 & 干预措施
Phase I: Group B (part 2)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information.
干预措施: Prednisone/Prednisolone (Drug)
Phase I: Group B (part 2)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Phase I: Group A (part 1)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT) throughout the study.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Phase II: Arm 1
Tulmimetostat Dose 1 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Phase II: Arm 2 (Optional)
Tulmimetostat Dose 2 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). This arm will be included if two recommended dose(s) for expansion are selected from Phase I.
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Phase II: Arm 3 (Control)
Darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).
干预措施: Androgen Deprivation Therapy (ADT) (Drug)
Phase II: Arm 3 (Control)
Darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).
干预措施: Darolutamide (Drug)
Phase II: Arm 2 (Optional)
Tulmimetostat Dose 2 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). This arm will be included if two recommended dose(s) for expansion are selected from Phase I.
干预措施: Tulmimetostat (Drug)
Phase II: Arm 2 (Optional)
Tulmimetostat Dose 2 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). This arm will be included if two recommended dose(s) for expansion are selected from Phase I.
干预措施: Darolutamide (Drug)
Phase I: Group A (part 1)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT) throughout the study.
干预措施: Tulmimetostat (Drug)
Phase I: Group B (part 2)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information.
干预措施: Tulmimetostat (Drug)
Phase I: Group B (part 2)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information.
干预措施: Abiraterone (Drug)
Phase I: Group A (part 1)
Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT) throughout the study.
干预措施: Darolutamide (Drug)
Phase II: Arm 1
Tulmimetostat Dose 1 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).
干预措施: Tulmimetostat (Drug)
Phase II: Arm 1
Tulmimetostat Dose 1 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT).
干预措施: Darolutamide (Drug)
结局指标
主要结局
Phase I (Group A and Group B): Dose-limiting toxicities (DLTs)
时间窗: From the first dose of study treatment through the end of Cycle 1, up to 28 days
A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value that was not clearly attributable to the underlying disease or an extraneous cause, occurred during the first 28 days of treatment with tulmimetostat, and met the protocol-defined dose-limiting toxicity criteria. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dose-limiting toxicities were included in the Bayesian Logistic Regression Model used to support dose-escalation decisions.
Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
The incidence, type, frequency, seriousness, and severity of adverse events and serious adverse events will be summarized. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
Phase I (Group A and Group B): Number of Participants with dose adjustments
时间窗: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
The number of participants with dose reductions, dose interruptions, or permanent discontinuations, including the reasons for the dose adjustments, will be summarized by treatment group and dose cohort.
Phase I (Group A and Group B): Dose Intensity
时间窗: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
Dose intensity, calculated as the actual cumulative dose received divided by the actual duration of exposure, and relative dose intensity, calculated as the dose intensity divided by the planned dose intensity, will be summarized using descriptive statistics for each study drug.
Phase I (Group A and Group B): Duration of exposure to each study drug
时间窗: From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months
The duration of exposure, in months, to each study drug will be summarized using descriptive statistics by treatment group and dose cohort.
Phase II (Group A): Prostate-Specific Antigen (PSA) response rate of < 0.2 ng/mL at Month 6
时间窗: At Month 6, with confirmation by a second prostate-specific antigen assessment performed at least 3 weeks later
Prostate-Specific Antigen (PSA) response rate is defined as the proportion of participants who achieved a prostate-specific antigen level below 0.2 ng/mL at Month 6, confirmed by a second prostate-specific antigen assessment performed at least 3 weeks later.
Phase I (Group A and Group B): Dose-limiting toxicities (DLTs)
时间窗: Up to 28 days
A dose-limiting toxicity is defined as an adverse event or abnormal laboratory value, not clearly due to underlying disease or extraneous causes, that occurs within the first 28 days of treatment with tulmimetostat and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose-escalation decisions, DLTs will be considered and included in the Bayesian Logistic Regression Model (BLRM).
Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Phase I (Group A and Group B): Number of Participants with dose adjustments
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Phase I (Group A and Group B): Dose Intensity
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics
Phase I (Group A and Group B): Duration of exposure to each study drug
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Duration of exposure (in months) to each study drug will be summarized by means of descriptive statistics
Phase I (Group A and Group B): Dose-limiting toxicities (DLTs)
时间窗: Up to 28 days
A dose-limiting toxicity is defined as an adverse event or abnormal laboratory value, not clearly due to underlying disease or extraneous causes, that occurs within the first 28 days of treatment with tulmimetostat and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose-escalation decisions, DLTs will be considered and included in the Bayesian Logistic Regression Model (BLRM).
Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
Phase I (Group A and Group B): Number of Participants with dose adjustments
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Phase I (Group A and Group B): Dose Intensity
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics
Phase I (Group A and Group B): Duration of exposure to each study drug
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Duration of exposure to each study drug will be summarized by means of descriptive statistics
Phase II (Group A): Biochemical Response Rate (BCR)
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Biochemical Response Rate (BCR) is defined as prostate-specific antigen (PSA) decline to \< 0.2 ng/mL at 6 months, confirmed by a second PSA measurement ≥ 3 weeks later.
Phase II (Group A): Prostate-Specific Antigen (PSA) response rate of < 0.2 ng/mL
时间窗: From date of randomization till 30 days safety fup, assessed up to approximately 79 months
Prostate-Specific Antigen (PSA) response rate is defined as proportion of participants who achieved a decline in PSA to \< 0.2 ng/mL at month 6 months, confirmed by a second PSA measurement ≥ 3 weeks later.
次要结局
- Phase II (Group A):Overall survival (OS)(From randomization until death from any cause, assessed up to approximately 79 months)
- Phase I (Group A): Plasma concentrations of Tulmimetostat and Darolutamide(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Cycle 1, Day 2: 0 and 24 hours post-dose for tulmimetostat; Cycle 1, Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days)
- Phase I (Group A): AUC of Tulmimetostat and Darolutamide(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Cycle 1, Day 2: 0 and 24 hours post-dose for tulmimetostat; Cycle 1, Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days)
- Phase I (Group A): Maximum Observed Plasma Concentration (Cmax) of Tulmimetostat and Darolutamide(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Cycle 1, Day 2: 0 and 24 hours post-dose for tulmimetostat; Cycle 1, Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days)
- Phase I (Group B): Plasma concentrations of Tulmimetostat and Abiraterone(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Day 2: 0 and 24 hours post-dose; Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days.)
- Phase I (Group B): AUC of Tulmimetostat and Abiraterone(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Day 2: 0 and 24 hours post-dose; Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days.)
- Phase I (Group B): Maximum Observed Plasma Concentration (Cmax) of Tulmimetostat and Abiraterone(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Day 2: 0 and 24 hours post-dose; Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days.)
- Phase II (Group A): Radiographic progression free survival (rPFS)(From randomization until the first documented radiographic disease progression or death from any cause, whichever occurs first, assessed up to approximately 79 months)
- Phase II (Group A): Objective Response Rate (ORR)(From randomization until disease progression, death, or the last adequate tumor assessment, assessed up to approximately 79 months)
- Phase II (Group A): Best Overall Response (BOR)(From randomization until disease progression or death from any cause, whichever occurred first, assessed up to approximately 79 months)
- Phase II (Group A): Duration of Response (DOR)(From the first documented complete or partial response until disease progression or death from any cause, whichever occurred first, assessed up to approximately 79 months)
- Phase II (Group A): Prostate-Specific Antigen 50 (PSA50) response rate(From randomization until the last prostate-specific antigen assessment, assessed up to approximately 79 months)
- Phase II (Group A): Prostate-Specific Antigen (PSA) Response below 0.1 ng/mL(From randomization until the last prostate-specific antigen assessment, assessed up to approximately 79 months)
- Phase II (Group A): Time to castration-resistant prostate cancer (CRPC)(From randomization until prostate-specific antigen progression, radiographic progression in bone, or radiographic progression in soft-tissue or visceral lesions, whichever occurred first, assessed up to approximately 79 months)
- Phase II (Group A): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months)
- Phase II (Group A): Number of Participants with dose adjustments(From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months)
- Phase II (Group A): Dose Intensity(From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months)
- Phase II (Group A): Duration of exposure to each study drug(From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months)
- Phase II (Group A): Plasma concentrations of tulmimetostat and darolutamide in participants included in intensive pharmacokinetic sampling(Cycles 1 and 2, Day 1: 0, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose; Cycle 1, Day 2: 0 and 24 hours post-dose for tulmimetostat; Cycle 1, Days 8 and 15: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days)
- Phase II (Group A): Plasma concentrations of Tulmimetostat(Cycles 1 and 2, Day 1: 0 and 2 hours post-dose; Cycles 3 to 5, Day 1: pre-dose. Each cycle is 28 days)
- Phase II (Group A): Time to first symptomatic skeletal event (TTSSE)(From the first dose of study treatment until the first symptomatic skeletal event, assessed up to approximately 79 months)
- Phase II (Group A): Number of Participants with dose adjustments(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Dose Intensity(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Duration of exposure to each study drug(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase I (Group A): Plasma concentrations of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group A): AUC of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group A): Cmax of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): Plasma concentrations of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): AUC of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): Cmax of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Radiographic progression free survival (rPFS)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 79 months)
- Phase II (Group A): Objective response (OR)(From date of randomization until date of confirmed Complete Response (CR) or Partial Response (PR), assessed up to approximately 79 months)
- Phase II (Group A): Best Overall response (BOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 79 months)
- Phase II (Group A): Duration of response (DOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 79 months)
- Phase II (Group A): Prostate-Specific Antigen 50 (PSA50)(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Time to castration-resistant prostate cancer (CRPC)(From date of randomization until date of PSA progression, radiological progression by bone lesions, or radiological progression by soft tissue and visceral lesions, whichever comes first, assessed up to approximately 79 months)
- Phase II (Group A): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Plasma concentrations of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): AUC of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Cmax of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Plasma concentrations of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): AUC of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Cmax of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Time to first symptomatic skeletal event (TTSSE)(From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 79 months.)
- Phase I (Group A): Plasma concentrations of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group A): AUC of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group A): Cmax of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): Plasma concentrations of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): AUC of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase I (Group B): Cmax of Tulmimetostat and Abiraterone(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours), Day 2 (0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Radiographic progression free survival (rPFS)(From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 79 months)
- Phase II (Group A):Overall survival (OS)(From date of randomization until date of death from any cause, assessed up to approximately 79 months)
- Phase II (Group A): Objective response (OR)(From date of randomization until date of confirmed Complete Response (CR) or Partial Response (PR), assessed up to approximately 79 months)
- Phase II (Group A): Best Overall response (BOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 79 months)
- Phase II (Group A): Duration of response (DOR)(From date of randomization until date of progression or date of death from any cause, whichever come first, assessed up to approximately 79 months)
- Phase II (Group A): Prostate-Specific Antigen 50 (PSA50)(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Biochemical Response of <0.1 ng/mL(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Time to castration-resistant prostate cancer (CRPC)(From date of randomization until date of PSA progression, radiological progression by bone lesions, or radiological progression by soft tissue and visceral lesions, whichever comes first, assessed up to approximately 79 months)
- Phase II (Group A): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Number of Participants with dose adjustments(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Dose Intensity(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Duration of exposure to each study drug(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
- Phase II (Group A): Plasma concentrations of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): AUC of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Cmax of Tulmimetostat and Darolutamide(Cycle 1-2: Day 1 (0 hour, 0.5 hours, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours and 8 hours). Cycle 1: Day 2 (Tulmimetostat only: 0 hour and 24 hours), Days 8 and 15 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Plasma concentrations of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): AUC of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Cmax of Tulmimetostat(Cycle 1-2: Day 1 (0 hour and 2 hours). Cycles 3-5: Day 1 (0 hour). 1 cycle = 28 days.)
- Phase II (Group A): Time to first symptomatic skeletal event (TTSSE)(From randomization until the first occurrence of a new symptomatic bone fracture, spinal cord compression, tumor-related orthopedic surgery, radiation therapy for bone pain, or death, assessed up to 79 months.)
- Phase II (Group A): Prostate-Specific Antigen (PSA) Response of <0.1 ng/mL(From date of randomization till 30 days safety fup, assessed up to approximately 79 months)
研究者
研究点 (34)
标识符
- NCT 编号
- NCT07190300
- 其他研究编号
- CDZR123C12101, 2025-521873-15-00, 2025
日期
- 首次提交
- (去年)
- 首次发布
- (去年)
- 主要完成日期
- (5年后)
- 研究完成日期
- (5年后)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com