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
- 200
- 试验地点
- 95
- 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 MSI or mismatch repair status.
- •Documented disease progression after having received ≥1 line of therapy (no more than 3), including PBC-containing systemic treatment and an anti-PD-1 therapy containing regimen (combined or sequential) in the advanced/metastatic setting.
- •Additional inclusion criteria for cervical cancer cohort
- •Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.
- •Disease progression after having received ≥1 prior line of therapy that includes systemic therapy in the advanced or metastatic setting.
- •Additional inclusion criterion for non-HGSOC cohort
- •a. Pathologically or cytologically documented unresectable or metastatic CCOC, low grade endometrioid, low-grade serous, or mucinous OVC that was previously treated with at least 1 prior line of therapy.
- •Additional inclusion criteria for urothelial cancer cohort
- •Pathologically or cytologically documented unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant.
- •Relapsed or progressed after treatment with ≥1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting.
- •Additional inclusion criterion for the ccRCC cohort a. Pathologically or cytologically documented unresectable or metastatic ccRCC that was previously treated with no more than 3 prior systemic regimens for locally advanced or metastatic RCC, including both a PD-(L)1 checkpoint inhibitor and a VEGF-TKI in sequence or in combination.
- •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.
- •Uncontrolled or significant cardiovascular disease as specified in the protocol.
- •Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Clinically severe pulmonary compromise
- •Chronic steroid treatment (>10 mg/day) 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 NCI-CTCAE Version 5.0, Grade ≤1 or baseline.
- •Prior exposure to other CDH6-targeted agents or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan, datopotamab deruxtecan).
- •Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- •Has active or uncontrolled HIV, HBV, or HCV infection.
排除标准
- 未提供
研究组 & 干预措施
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)
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)
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 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 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))
- 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)