A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01)

Trial Title: A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01)

NCT ID: NCT06660654

Condition: Advanced Solid Tumor
Metastatic Solid Tumors

Conditions: Official terms:
Neoplasms

Conditions: Keywords:
Advanced/metastatic solid tumors
Raludotatug Deruxtecan
R-DXd
DS-6000

Study type: Interventional

Study phase: Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Raludotatug deruxtecan
Description: IV administration Q3W
Arm group label: Cervical Cancer Cohort
Arm group label: Clear Cell Renal Carcinoma (ccRCC) Cohort
Arm group label: Endometrial Cancer Cohort
Arm group label: Non-high-grade Serous Ovarian Cancer
Arm group label: Urothelial Cancer Cohort

Other name: R-DXd

Summary: 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]).

Detailed description: 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.

Criteria for eligibility:
Criteria:
Participants must meet all of the following criteria to be eligible for enrollment into the trial: 1. Adults ≥18 years of age on the day of signing the ICF. 2. Participants must have at least 1 lesion, not previously irradiated, amenable to biopsy, and must consent to provide a pre-treatment biopsy from a primary and/or metastatic lesion. 3. Has at least 1 measurable lesion according to RECIST version 1.1 per investigator assessment. 4. Participants must have progressed radiologically on or after their most recent line of systemic therapy. 5. Eastern Cooperative Oncology Group performance status of 0 or 1. 6. Additional inclusion criteria for endometrial cancer cohort 1. Pathologically or cytologically documented endometrial cancer (carcinoma of any histological subtype or carcinosarcoma), irrespective of MSI or mismatch repair status. 2. 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. 7. Additional inclusion criteria for cervical cancer cohort 1. Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix. 2. Disease progression after having received ≥1 prior line of therapy that includes systemic therapy in the advanced or metastatic setting. 8. 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. 9. Additional inclusion criteria for urothelial cancer cohort 1. 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. 2. 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. 10. 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: 1. Clinically active brain metastases, spinal cord compression, or leptomeningeal carcinomatosis 2. Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event. 3. Uncontrolled or significant cardiovascular disease as specified in the protocol. 4. 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. 5. Clinically severe pulmonary compromise 6. Chronic steroid treatment (>10 mg/day) with exceptions as noted in the protocol. 7. 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. 8. 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. 9. 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). 10. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. 11. Has active or uncontrolled HIV, HBV, or HCV infection.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Clinical Research Alliance

Address:
City: Westbury
Zip: 11590
Country: United States

Contact:
Last name: Principal Investigator

Start date: December 31, 2024

Completion date: September 30, 2027

Lead sponsor:
Agency: Daiichi Sankyo
Agency class: Industry

Collaborator:
Agency: Merck Sharp & Dohme LLC
Agency class: Industry

Source: Daiichi Sankyo

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06660654