Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
- Sign and date the informed consent form prior to the start of any study-specific
qualification procedures.
- Age ≥18 years or the minimum legal adult age (whichever is greater) at the time the
informed consent form is signed.
- Participants with histologically or cytologically documented high-grade serous ovarian
cancer (OVC), high-grade endometrioid OVC, primary peritoneal cancer, or fallopian
tube cancer.
- Participants must have at least 1 lesion, not previously irradiated, amenable to
biopsy, and must consent to provide a pretreatment biopsy and on-treatment biopsy
tissue sample (on-treatment biopsy sample not required for the Phase 3 part of the
study).
- Has received at least 1 but no more than 3 prior systemic lines of anticancer therapy.
- Has platinum-resistant disease. If a subject had only 1 line of platinum therapy, must
have received at least 4 cycles of platinum, must have had a best response of not PD,
and then progressed between >90 and ≤180 days after the date of the last dose of
platinum If a subject had 2 or 3 lines of platinum therapy, must have received at
least 2 cycles of platinum and have progressed on or within 180 days after the date of
the last dose of platinum.
- Has had prior poly-ADP ribose polymerase (PARP) inhibitors for participants with
documented breast cancer gene mutation (germline and/or somatic), unless the
participant is not eligible for treatment with a PARP inhibitor.
- Has had prior treatment with mirvetuximab soravtansine for participants with
documented high-folate receptor alpha expression, unless the participant is not
eligible for treatment with mirvetuximab soravtansine due to precautions/intolerance,
or if the treatment is not approved or available locally.
- Has at least 1 measurable lesion evaluated by computed tomography or magnetic
resonance imaging according to Response Evaluation Criteria in Solid Tumors version
1.1 (RECIST v1.1) per investigator assessment.
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Required baseline local laboratory data (within 7 days before start of study drug
administration).
- If the participant is a female of childbearing potential, she must have a negative
serum pregnancy test at 72 hours before the first dose of study drug and must be
willing to use highly effective birth control upon enrollment, during the Treatment
Period, and for 7 months following the last dose of study drug.
- Female participants must not donate, or retrieve for their own use, ova from the time
of screening and throughout the study treatment period, and for at least 7 months
after the final study drug administration.
- Is willing and able to comply with scheduled visits, drug administration plan,
laboratory tests, other study procedures, and study restrictions.
- For Phase 3 (Part B) only: Participants must be eligible for one of the treatments
included in the Investigator's choice of chemotherapy arm and must not have received
it previously for OVC.
Exclusion Criteria
- Has clear cell, mucinous, or sarcomatous histology; mixed tumors containing any
histology; or low-grade/borderline OVC.
- Clinically active brain metastases, spinal cord compression, or leptomeningeal
carcinomatosis, defined as untreated or symptomatic, or requiring therapy with
steroids or anticonvulsants to control associated symptoms.
- Any of the following within the past 6 months prior to randomization: cerebrovascular
accident, transient ischemic attack, or other arterial thromboembolic event.
- Uncontrolled or significant cardiovascular disease
- Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that
required corticosteroids, has current ILD/pneumonitis, or where suspected
ILD/pneumonitis cannot be ruled out by imaging at screening.
- Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
including, but not limited to, any underlying pulmonary disorder and any autoimmune,
connective tissue, or inflammatory disorders with potential pulmonary involvement or
prior pneumonectomy.
- Chronic steroid treatment (>10 mg/day)
- History of malignancy other than epithelial OVC, primary peritoneal cancer, or
fallopian tube cancer within 3 years prior to enrollment
- 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 Version 5.0 Grade ≤1 or baseline.
- Prior exposure to other CDH6-targeted agents or an antibody-drug conjugate that
consists of an exatecan derivative that is a topoisomerase I inhibitor (eg,
trastuzumab deruxtecan or datopotamab deruxtecan).
- History of hypersensitivity to any excipients in the R-DXd or any known
contraindication to treatment with, including hypersensitivity to, the study drug(s).
- Has a known human immunodeficiency virus (HIV) infection that is not well controlled.
Participants must be tested for HIV viral load during the Screening Period if
acceptable by local regulations or institutional review boards/ethics committees.
- Has any evidence of severe or uncontrolled systemic diseases (including active
bleeding diatheses or active infection, substance abuse) or other factors that, in the
investigator's opinion, makes it undesirable for the participant to participate in the
study or which would jeopardize compliance with the protocol.
- Has an active or uncontrolled hepatitis B and/or hepatitis C infection. Participants
must be tested for hepatitis B (hepatitis B surface antigen [HBsAg] and anti-hepatitis
B core antigen) and hepatitis C (hepatitis C virus [HCV] antibody) during the
Screening Period. Participants are eligible if they meet the following conditions.
- Female who is pregnant or breastfeeding or intends to become pregnant during the
study.
- Psychological, social, familial, or geographical factors that would prevent regular
follow-up.
- Prior or ongoing clinically relevant illness, medical condition, surgical history,
physical finding, or laboratory abnormality that, in the investigator's opinion, could
affect the safety of the participants ; alter the absorption, distribution,
metabolism, or excretion of the study drug; or confound the assessment of study
results.
- Has a history of receiving live-attenuated vaccine (messenger RNA [mRNA] and
replication-deficient adenoviral vaccines are not considered attenuated live vaccines)
within 30 days prior to the first exposure to study intervention.
- For Phase 3 (Part B) only: Participants are ineligible if they have a history of any
contraindication included in the approved local label for the control group treatment.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 1/25/24. Questions regarding updates should be directed to the study team contact.