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

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 \[ccRCC\]).

Participants must meet all of the following criteria to be eligible for enrollment into the trial: 1. Adults greater than or equal to ( ≥) 18 years of age on the day of signing the informed consent form (ICF). 2. Participants must have at least 1 lesion, 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. Adequate organ/bone marrow function. 7. Additional inclusion criteria for endometrial cancer cohort: 1. 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. 2. 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. 8. Additional inclusion criterion for non-HGSOC cohort: 1. 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. 2. 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: 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 (e.g., intestinal ischemia). 3. Uncontrolled or significant cardiovascular disease as specified in the protocol. 4. 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. 5. Clinically severe pulmonary compromise. 6. Chronic steroid treatment (greater than \[\>\]10 mg/day prednisone \[or equivalent\]) 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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0, Grade less than or equal to (≤)1 or baseline. 9. 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). 10. Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection. 11. Has active or uncontrolled human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection