Clinical trial NCT06660654: A Study of Raludotatug Deruxtecan in Participants With Advanced/Metastatic Solid Tumors (REJOICE-PanTumor01)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Advanced Solid Tumor
Metastatic Solid Tumors
Keywords: Advanced/metastatic solid tumors
Raludotatug Deruxtecan
R-DXd
DS-6000
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2024-10-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC)
timeFrame: Baseline up to 32 months
measure: Disease Control Rate (DCR) as Assessed by the Investigator (ccRCC Cohort Only)
timeFrame: Baseline up to 32 months
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) (All Cohorts)
timeFrame: Baseline up to 32 months
Secondary outcomes:
measure: Progression-free Survival (PFS) as Assessed by the Investigator
timeFrame: Baseline up to 32 months
measure: Duration of Response (DoR) as Assessed by the Investigator
timeFrame: Baseline up to 32 months
measure: Time to Response (TTR) as Assessed by the Investigator
timeFrame: Baseline up to 32 months
measure: Objective Response Rate as Assessed by the Investigator (ccRCC Cohort Only)
timeFrame: Baseline up to 32 months
measure: Disease Control Rate (DCR) as Assessed by the Investigator (All Cohorts Except ccRCC Cohort)
timeFrame: Baseline up to 32 months
measure: Pharmacokinetic Parameter Maximum Concentration (Cmax) of R-DXd
timeFrame: 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)
measure: The Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive At Any Time and Who Have a Treatment-emergent ADA
timeFrame: Baseline up to 32 months
Other outcomes:
Locations:
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: Albany
country: United States
facility: Women's Cancer Care Associates
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Catania
country: Italy
facility: AO per lEmergenza Cannizzaro
city: Genova
country: Italy
facility: Irccs Ospedale San Martino
city: Meldola
country: Italy
facility: IRCCS Dino Amadori - IRST
city: Terni
country: Italy
facility: Azienda Ospedaliera S Maria
city: Akashi
country: Japan
facility: Hyogo Cancer Center
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Jfcr
Study officials:
References: