REJOICE-PanTumor01: A Phase 2, Multicenter, Open-Label, Pan-Tumor Trial to Evaluate Efficacy and Safety of Raludotatug Deruxtecan (R-DXd) in Participants With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 335
- 试验地点
- 90
- 主要终点
- Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
研究概览
简要总结
This pan-tumor trial is designed as a signal-seeking trial to assess efficacy and safety of raludotatug deruxtecan (R-DXd) monotherapy in locally advanced or metastatic solid tumors with various cadherin-6 (CDH6) expression levels, including gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and clear cell renal cell carcinoma [ccRCC]).
详细描述
This trial is designed to evaluate the efficacy and safety of R-DXd in locally advanced or metastatic solid tumors with various CDH6 expression levels. Solid tumor types will include gynecological cancers (endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer) and genitourinary cancers (urothelial cancer and ccRCC).
For all cohorts except ccRCC, the primary endpoint will be objective response rate (ORR) by investigator assessment per RECIST 1.1. For the ccRCC cohort, the primary endpoint will be disease control rate (DCR) by investigator assessment per RECIST 1.1. All cohorts will also have the assessment of safety and tolerability as another primary objective.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for endometrial cancer cohort:
- •Pathologically or cytologically documented endometrial cancer (carcinoma of any histological subtype or carcinosarcoma), irrespective of microsatellite instability (MSI) or mismatch repair status: small cell/neuroendocrine tumors are not allowed even if mixed histology.
- •Documented disease progression after having received ≥1 line of therapy (no more than 3), including platinum-based chemotherapy (PBC)-containing systemic treatment and an anti-PD-(L)1 therapy containing regimen (combined or sequential) in the advanced/metastatic setting.
- •Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose.
- •Prior hormonal therapy is not counted as a line of therapy in regard to the maximum allowed lines of treatment.
- •Additional inclusion criterion for non-HGSOC cohort:
- •Pathologically or cytologically documented unresectable or metastatic CCOC, low-grade endometrioid (Grade2 or lower), low-grade serous (Grade2 or lower), or mucinous OVC, from ovary, fallopian tube or peritoneum origin that was previously treated with at least 1 prior line of therapy.
- •Neo-adjuvant/adjuvant systemic therapies are counted as 1 line of therapy if there was progression or recurrence within 1 year from the final dose.
- •In Stage 3 only, participants with pathologically or cytologically documented unresectable or metastatic CCOC can be enrolled. Prior line of therapy requirements remains unchanged.
- •Participants who meet any of the following criteria will be disqualified from entering the trial:
- •Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis.
- •Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event (e.g., intestinal ischemia).
- •Uncontrolled or significant cardiovascular disease as specified in the protocol.
- •Has any history of (noninfectious) interstitial lung disease (ILD)/pneumonitis irrespective of steroid use, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Clinically severe pulmonary compromise.
- •Chronic steroid treatment (greater than [>]10 mg/day prednisone [or equivalent]) with exceptions as noted in the protocol.
- •History of other active malignancy within 3 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (eg, 5-year OS rate >90%) and treated with expected curative outcome.
- •Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0, Grade less than or equal to (≤)1 or baseline.
- •Prior exposure to other CDH6-targeted agents or an antibody drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (e.g., trastuzumab deruxtecan, datopotamab deruxtecan).
- •Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- •Has active or uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
排除标准
- 未提供
研究组 & 干预措施
Cervical Cancer Cohort
Participants with cervical cancer who will receive R-DXd administered intravenously Q3W.
干预措施: Raludotatug deruxtecan (Drug)
Urothelial Cancer Cohort
Participants with urothelial cancer who will receive R-DXd administered intravenously Q3W.
干预措施: Raludotatug deruxtecan (Drug)
Clear Cell Renal Carcinoma (ccRCC) Cohort
Participants with clear cell renal carcinoma (ccRCC) who will receive R-DXd administered intravenously Q3W.
干预措施: Raludotatug deruxtecan (Drug)
Non-high-grade Serous Ovarian Cancer
Participants with non-high-grade serous ovarian cancer who will receive R-DXd administered intravenously Q3W.
干预措施: Raludotatug deruxtecan (Drug)
Endometrial Cancer Cohort
Participants with endometrial cancer who will receive raludotatug deruxtecan (R-DXd) administered intravenously every 3 weeks (Q3W).
干预措施: Raludotatug deruxtecan (Drug)
结局指标
主要结局
Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
时间窗: Baseline up to 48 months
Objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
Disease Control Rate (DCR) as Assessed by the Investigator (ccRCC Cohort Only)
时间窗: Baseline up to 48 months
DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (maintained for ≥5 weeks) according to RECIST version 1.1.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
时间窗: Baseline up to 48 months
Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
时间窗: Baseline up to 32 months
Objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST version 1.1 criteria.
Disease Control Rate (DCR) as Assessed by the Investigator (ccRCC Cohort Only)
时间窗: Baseline up to 32 months
Disease control rate (DCR) is defined as proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (maintained for ≥5 weeks) according to RECIST version 1.1.
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
时间窗: Baseline up to 32 months
次要结局
- Progression-free Survival (PFS) as Assessed by the Investigator(Baseline up to 48 months)
- Duration of Response (DoR) as Assessed by the Investigator(Baseline up to 48 months)
- Time to Response (TTR) as Assessed by the Investigator(Baseline up to 48 months)
- Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)(Baseline up to 48 months)
- Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)(Baseline up to 48 months)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) of R-DXd(Cycles 1 and 3 Day 1 predose and end of infusion (EOI), 3 hours (hr), and 5 hr postdose; Cycle 1 Days 8, 15, and 22; Cycle 2 Day 1 predose and EOI postdose; Cycle 4 (and every 2 cycles thereafter) predose, up to 48 months (each cycle is 21 days))
- The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have a Treatment-emergent ADA(Baseline up to 48 months)
- The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have a Treatment-emergent ADA(Baseline up to 32 months)
- Progression-free Survival (PFS) as Assessed by the Investigator(Baseline up to 32 months)
- Duration of Response (DoR) as Assessed by the Investigator(Baseline up to 32 months)
- Time to Response (TTR) as Assessed by the Investigator(Baseline up to 32 months)
- Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)(Baseline up to 32 months)
- Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)(Baseline up to 32 months)
- Pharmacokinetic Parameter Maximum Concentration (Cmax) of R-DXd(Cycles 1 and 3 Day 1 predose and end of infusion (EOI), 3 hours (hr), and 5 hr postdose; Cycle 1 Days 8, 15, and 22; Cycle 2 Day 1 predose and EOI postdose; Cycle 4 (and every 2 cycles thereafter) predose, up to 32 months (each cycle is 21 days))