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 \[ccRCC\]).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Objective Response Rate as Assessed by the Investigator (All Cohorts Except ccRCC) — Baseline up to 48 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) — Baseline up to 48 months DCR is defined as the 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) — Baseline up to 48 months
Trial sites (48)
Facility
City
Region
Status
Northside Hospital
Marietta
Georgia
University of Michigan Comprehensive Cancer Center Michigan Medicine
Ann Arbor
Michigan
Astera Cancer Care
East Brunswick
New Jersey
Women's Cancer Care Associates
Albany
New York
Memorial Sloan-Kettering Cancer Center
New York
New York
Clinical Research Alliance
Westbury
New York
West Cancer Center and Research Institute
Germantown
Tennessee
The University of Texas MD Anderson Cancer Center
Houston
Texas
UZ Leuven Gynaec onco
Leuven
Belgium
ZAS Sint-Augustinus
Wilrijk
Belgium
Hunan Cancer Hospital
Changsha
China
Shanghai Cancer center
Shanghai
China
Herlev og Gentofte Hosp
Copenhagen
Denmark
François Baclesse Center
Caen
France
Centre Georges-François Leclerc
Dijon
France
Centre Oscar Lambret
Lille
France
Centre Leon Berard
Lyon
France
Grp Hsp Diac Croix Saint Simon
Paris
France
Cario - Centre Armoricain de Radiothérapie, Imagerie Médicale Et Oncologie
Plérin
France
Ico - Site René Gauducheau
Saint-Herblain
France
Institut Claudius Regaud
Toulouse
France
Gustave Roussy
Villejuif
France
AO per lEmergenza Cannizzaro
Catania
Italy
Irccs Ospedale San Martino
Genova
Italy
IRCCS Dino Amadori - IRST
Meldola
Italy
IRCCS San Raffaele
Milan
Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan
Italy
Federico II Hospital
Naples
Italy
Azienda Ospedaliera S Maria
Terni
Italy
Hyogo Cancer Center
Akashi
Japan
National Cancer Center Hospital
Chūōku
Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka
Japan
Saitama Medical University International Medical Center
Hidaka
Japan
National Cancer Center Hospital East
Kashiwa
Japan
The Cancer Institute Hospital of Jfcr
Kōtoku
Japan
Aichi Cancer Centre
Nagoya
Japan
Osaka International Cancer Institute
Osaka
Japan
National Cancer Center
Goyang-si
South Korea
Severance Hospital
Seoul
South Korea
Asan Medical Center
Seoul
South Korea
+ 8 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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