Condition médicale (spécialité visée)
Choix aire thérapeutique
Cancérologie / Radio-oncologie/ tumeurs solides
Santé des femmes (Obstétrique, gynécologie)
Stades de cancer
Rechute
Avancé
Biomarqueur
CA125
Autre :
HRD -
Profil des participants
Sexe(s) des participants
Femmes
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
1.Has pathologically documented diagnosis of high-grade serous epithelial ovarian cancer,
primary peritoneal cancer, or fallopian tube cancer.
2. Has measurable disease per RECIST 1.1, as assessed by the investigator. Lesions situated
in a previously irradiated area are considered measurable if progression has been shown
in such lesions.
3. Cohort A-1 Arm 2 and Arm 3: Has relapsed disease after 1 to 3 prior lines of therapy and
radiographic evidence of disease progression ≥6 months (≥180 days) after the last dose of
platinum-based therapy (ie, platinum-sensitive disease). Refer to Section 8.1.6.1 for the
definition of prior lines of therapy.
4. Cohort B-1 and Cohort B-2: Has relapsed disease after 1 to 3 prior lines of therapy and
radiographic evidence of disease progression <6 months (<180 days) after the last dose of
platinum-based therapy (ie, platinum-resistant disease). Refer to Section 8.1.6.1 for the
definition of prior lines of therapy.
Note: Participants with primary platinum-refractory ovarian cancer (defined as disease
that has progressed on or within 12 weeks after the first platinum-based therapy) are not
eligible.
5. Cohort B-1 and Cohort B-2: Participant is a candidate for bevacizumab treatment.
6. Has provided a tissue sample for biomarker research (most recent sample is preferred)
from a core or excisional biopsy of a tumor lesion not previously irradiated. Details
pertaining to tumor tissue submission are provided in the Central Laboratory Manual.
Tissue is required for testing by the Central Laboratory.
Participants who have AEs due to previous anticancer therapies must have recovered to
Grade ≤1 or baseline (except alopecia or vitiligo). Participants with endocrine-related
AEs who are adequately treated with hormone replacement are eligible.
7. An ECOG Performance Status of 0 to 1 assessed within 7 days before allocation.
8. HIV-infected participants must have well controlled HIV on ART, defined as:
a. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of
screening
b. Participants on ART must have achieved and maintained virologic suppression
defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of
detection) using the locally available assay at the time of screening and for at least
9. weeks before screening
c. It is advised that participants must not have had any AIDS-defining opportunistic
infections within the past 12 months
d. Participants on ART must have been on a stable regimen, without changes in drugs or
dose modification, for at least 4 weeks before study entry (Day 1) and agree to
continue ART throughout the study
10. Participants who are HBsAg positive are eligible if they have received HBV antiviral
therapy for at least 4 weeks, and have undetectable HBV viral load prior to allocation.
Note: Participants should remain on antiviral therapy throughout study intervention and
follow local guidelines for HBV antiviral therapy post completion of study intervention.
Hepatitis B screening tests are not required unless:
- Known history of HBV infection
- As mandated by local guidelines
11. Participants with history of HCV infection are eligible if HCV viral load is undetectable
at screening.
Note: Participants must have completed curative antiviral therapy at least 4 weeks prior
to allocation.
Hepatitis C screening tests are not required unless:
- Known history of HCV infection
- As mandated by local guidelines
12. Adequate organ function as defined in the following table (Table 6). Specimens must be
collected within 7 days before allocation.
Critères d'exclusion
Any of the following within 6 months before allocation: cerebrovascular accident,
transient ischemic attack, or other arterial thromboembolic event.
2. Uncontrolled or significant cardiovascular disease, including the following:
• QTcF interval >470 ms (average of triplicate determinations at Screening).
• Diagnosed or suspected long QT syndrome.
• History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia,
ventricular fibrillation, or Torsade de Pointes.
• Bradycardia of less than 50 bpm, unless the participant has a pacemaker.
History of second- or third-degree heart block. Candidates with a history of heart
block may be eligible if they currently have pacemakers and have no history of
fainting or clinically relevant arrhythmia with pacemakers.
• Myocardial infarction within 6 months before Screening.
• Uncontrolled angina pectoris within 6 months before Screening.
• New York Heart Association Class 3 or 4 congestive heart failure.
• LVEF <50% or institutional lower limit of normal as measured by echocardiography
or MUGA scan.
• Coronary/peripheral artery bypass graft within 6 months before Screening.
• Grade ≥3 hypertension as per NCI CTCAE version 5.0.
• Complete left or right bundle branch block.
Has clinically severe pulmonary compromise resulting from intercurrent pulmonary
illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary
emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive
lung disease, etc), and any autoimmune, connective tissue, or inflammatory disorders
with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren’s syndrome,
sarcoidosis), or prior pneumonectomy.
4. Has ≥Grade 2 peripheral neuropathy.
5. Cohort B-1, Cohort B-2, and if administering bevacizumab is planned in Cohort D: Has
current, clinically relevant bowel obstruction (including subocclusive disease) including
obstruction related to underlying epithelial ovarian cancer, abdominal fistula or
gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid
involvement by pelvic exam.
Note: This applies only to participants who will receive bevacizumab.
6. Cohort B-1, Cohort B-2, and if administering bevacizumab is planned in Cohort D: Has a
history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal
bleeding within 6 months before allocation.
Note: Participants with venous thromboembolic events that occurred >6 months before
allocation and are well controlled on therapy are eligible for the study.
The above criteria apply only to participants who will receive bevacizumab.
Prior treatment with CDH6-targeted agents.
8. Prior treatment with an ADC containing a topoisomerase I inhibitor (eg, trastuzumab
deruxtecan, datopotamab deruxtecan).
9. Received chloroquine or hydroxychloroquine within 14 days before allocation.
10. Received prior systemic anticancer therapy including investigational agents within
4 weeks or 5 half-lives (whichever is shorter) before allocation.
Received prior radiotherapy within 2 weeks of the start of study intervention, or has
radiation-related toxicities, requiring corticosteroids.
Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted.
The last palliative radiotherapy treatment must have been performed at least 7 days
before the first dose of study intervention.
12. Received a live or live-attenuated vaccine within 30 days before the first dose of study
intervention. Administration of killed vaccines is allowed.
13. Receives chronic steroid treatment (>10 mg prednisone [or equivalent] per day), with the
exception of the following:
• Inhaled steroids for asthma or COPD
• Mineralocorticoids (eg, fludrocortisone) for participants with orthostatic hypotension
• Topical steroids for mild skin conditions
• Low-dose supplemental corticosteroids for adrenocortical insufficiency
• Premedication for treatment groups and/or premedication in case of any
hypersensitivity
• Intraarticular steroid injections
14. Cohort B-1, Cohort B-2, and if administering bevacizumab is planned in Cohort D:
Bevacizumab is contraindicated or was previously discontinued due to an AE considered
related to bevacizumab.
Has received an investigational agent or has used an investigational device within
4 weeks prior to study intervention administration.
Known additional malignancy that is progressing or has required active treatment within
the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the
skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have
undergone potentially curative therapy are not excluded.
17. Known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat
imaging performed during the study screening, are clinically stable and have not required
steroid treatment for at least 14 days before the first dose of study intervention.
18. History of (noninfectious) pneumonitis/ILD that required steroids or has current
pneumonitis/ILD, or where suspected ILD/pneumonitis cannot be ruled out by standard
diagnostic assessments at screening.
19. Active infection requiring systemic therapy.
20. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric
Castleman’s Disease.
Severe hypersensitivity (≥Grade 3) to R-DXd and/or any of its excipients, or other
biologic therapy.
22. For Cohort A-1 Arm 3: Severe hypersensitivity (≥Grade 3) to carboplatin and/or any of
its excipients.
23. For Cohort A-1 Arm 2: Severe hypersensitivity (≥Grade 3) to paclitaxel and/or any of its
excipients.
24. For Cohort B-1, Cohort B-2 and if administering bevacizumab is planned in Cohort D:
Severe hypersensitivity (≥Grade 3) to bevacizumab and/or any of its excipients
Note: This applies to all participants who will receive bevacizumab. Participants with
known sensitivity to Chinese Hamster Ovary cell products or other recombinant human
or humanized antibodies are prohibited from receiving bevacizumab during the study.
25. History or current evidence of any condition, therapy, laboratory abnormality, or other
circumstance that might confound the results of the study or interfere with the
participant's ability to cooperate with the requirements of the study, such that it is not in
the best interest of the participant to participate, in the opinion of the treating investigator.
26. Participants who have not adequately recovered from major surgery or have ongoing
surgical complications.
Note: For all participants who will receive bevacizumab, surgery must have been at least
28 days before allocation.
27. Criterion removed.
28. For Cohort C-1: Diagnosis of immunodeficiency or is receiving immunosuppressive
therapy within 7 days prior to the first dose of study intervention.
29. For Cohort C-1: Active autoimmune disease that has required systemic treatment in the
past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
is allowed.
30. For Cohort C-1: History of stem cell/solid organ transplant.
31. For Cohort C-1: Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2
agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg,
CTLA-4, OX-40, CD137).
32. For Cohort C-1: Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.