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

Eligibility: Inclusion 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.