A Study to Investigate Mocertatug Rezetecan With Bevacizumab Compared With Platinum Doublet With Bevacizumab in Participants With Platinum-sensitive Ovarian Cancer (BEHOLD-Ovarian02)

Официальное название

A Randomized, Open-Label, Multicenter, Phase 3 Study to Investigate Mocertatug Rezetecan With Bevacizumab Compared With Platinum Doublet With Bevacizumab in Participants With Platinum-Sensitive Ovarian Cancer

Обзор

This study specifically aims to evaluate how well mocertatug rezetecan (Mo-Rez) in combination with bevacizumab works in treating platinum-sensitive ovarian cancer compared to standard treatments by checking whether it makes cancers smaller or disappear completely and if it helps participants live longer. The study also assesses whether Mo-Rez in combination with bevacizumab is safe and tolerated well by participants compared to standard treatments and aims to provide a better understanding of the main side effects of Mo-Rez.

Вмешательства

• Препарат Mocertatug rezetecan (Mo-Rez)
  Mocertatug rezetecan will be administered
• Препарат Carboplatin
  Carboplatin will be administered
• Препарат Paclitaxel
  Paclitaxel will be administered
• Препарат Gemcitabine
  Gemcitabine will be administered
• Препарат Pegylated liposomal doxorubicin (PLD)
  PLD will be administered
• Препарат Bevacizumab
  Bevacizumab will be administered

Первичные конечные точки

• Progression Free Survival (PFS) by BICR [Срок оценки: Up to approximately 191 weeks]

Вторичные конечные точки (12)

• Overall Survival (OS) [Срок оценки: Up to approximately 343 weeks]
• PFS by investigator assessment [Срок оценки: Up to approximately 343 weeks]
• Time to Second Progression (PFS2) [Срок оценки: Up to approximately 343 weeks]
• Objective response rate (ORR) by investigator assessment [Срок оценки: Up to approximately 343 weeks]
• Duration of Response (DOR) by investigator assessment [Срок оценки: Up to approximately 343 weeks]
• ORR by BICR [Срок оценки: Up to approximately 343 weeks]
• DOR by BICR [Срок оценки: Up to approximately 343 weeks]
• Time to first subsequent therapy (TFST) [Срок оценки: Up to approximately 343 weeks]
• Time to second subsequent therapy (TSST) [Срок оценки: Up to approximately 343 weeks]
• Number of participants with Treatment-emergent adverse event (TEAEs), Adverse event of special interest (AESIs) and Treatment-emergent serious adverse event (TESAEs) [Срок оценки: Up to approximately 343 weeks]
• Number of participants with TEAEs leading to dose modifications or study intervention discontinuation [Срок оценки: Up to approximately 343 weeks]
• Number of participants with changes in vital signs, laboratory tests (hematology and clinical chemistry), and Electrocardiogram (ECG) [Срок оценки: Up to approximately 343 weeks]

Критерии участия

Критерии включения

• Is at least 18 years of age and the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the Informed Consent Form (ICF).
• Has epithelial ovarian, primary peritoneal, or fallopian-tube cancer with a histologically confirmed diagnosis of high grade serous, high grade endometrioid, clear cell carcinoma, or carcinosarcoma.
• Has recurrent or progressive disease after completion of at least 1 and a maximum of 2 previous lines of systemic anticancer therapy. Recurrent or progressive disease should be determined based on radiographic assessment according to RECIST 1.1 per investigator and/or clinical assessment of disease progression by investigator. Prior lines of therapy are defined as follows:

• Adjuvant ± neoadjuvant is considered one line of therapy.
• Maintenance therapy (e.g., bevacizumab, Poly ADP-ribose polymerase inhibitor \[PARPi\]) will be considered as part of the preceding line of therapy (i.e., not counted independently).
• Therapy changed to another agent in the same class due to toxicity, in the absence of progression, will be considered as part of the same line (i.e., not counted independently).
• Unplanned addition or switching to a new drug in a different class is considered a separate line of therapy
• Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance.
• Has platinum-sensitive disease and is suitable for platinum doublet chemotherapy with bevacizumab for the treatment of recurrent disease. Platinum sensitive disease is defined as recurrent or progressive disease >6 months after last dose of platinum-based chemotherapy.
• Has documented results of local testing (compliant to local regulations) for tumor and/or germline Breast Cancer Gene (BRCA1 and BRCA2) mutation. Participants with a known tumor or germline deleterious BRCA1 or BRCA2 mutation must have previously received PARPi maintenance therapy, alone or in combination with bevacizumab, if the participant was considered a candidate for this treatment and the treatment is locally available.
• Has provided a Formalin Fixed Paraffin Embedded (FFPE) tumor tissue sample sufficient for the central assessment of B7 homolog 4 protein (B7-H4) expression, with the result of B7-H4 expression testing available prior to the date of randomization.
• Is willing to use adequate contraception. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• A female participant is eligible to participate if they are not pregnant or breastfeeding, and 1 of the following conditions applies:

• Is a Participant of Non-Childbearing Potential (PONCBP). OR
• Is a Participant of Childbearing Potential (POCBP) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, 30 days prior to Cycle 1 Day 1 (C1D1) and during the study intervention period and for at least 8 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A POCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
• Is capable of giving signed informed consent including compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function.

Критерии исключения

• Plans to undergo interval secondary cytoreductive surgery for recurrent PSOC during induction therapy (platinum doublet and bevacizumab).
• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 36 months prior to the date of randomization, except for basal cell or squamous cell carcinomas of the skin or in situ carcinomas (e.g., breast, cervix, bladder) that have been resected with no evidence of metastatic disease, or that is otherwise considered cured by the investigator.
• Has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Has untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g., evidence of new or enlarging brain metastasis or new neurologic symptoms attributable to brain/CNS metastases). Participants with previously treated and clinically stable brain/CNS metastases and who have completed all corticosteroid therapy for ≥14 days prior to the date of C1D1 are not excluded from participation.
• Has any evidence of current Interstitial Lung Disease (ILD) or pneumonitis or a prior history of ILD or non-infectious pneumonitis.
• Has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to Grade ≤1 or to the baseline status preceding prior therapy, excluding alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, Grade 2 neuropathy or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Has any serious and/or unstable medical condition (including infection) or any serious and/or unstable psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.
• Has clinically significant wound healing complications or incompletely healed wounds.
• Has a history or evidence of gastrointestinal perforation, tracheoesophageal fistula, or any Grade 4 fistula; has gastrointestinal fistula, visceral fistula, or abdominal abscess within 6 months prior to the date of C1D1; has osteonecrosis of the jaw.
• Has evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction.
• Has clinically significant bleeding symptoms, significant bleeding tendency, or bleeding tumors within 30 days prior to the date of C1D1.
• Has congenital bleeding diathesis, acquired coagulopathy, recent pulmonary hemorrhage/hemoptysis (>2.5 mL of red blood or a half teaspoon) within 3 months prior to the date of C1D1.
• Has had any major surgery within 28 days prior to the date of C1D1 or history of focal radiotherapy within 21 days prior to the date of C1D1.
• Has received treatment with an investigational agent within 30 days prior to the date of C1D1.
• Has ever received prior therapy with topoisomerase 1 inhibitor \[Topo1i\] (e.g., topotecan) or antibody-Drug Conjugate (ADC) with a Topo1i warhead, or B7-H4 targeted therapy.
• Has received treatment with any cytotoxic chemotherapy drugs or other antitumor drugs (including endocrine therapy, molecular targeted therapy, immunotherapy or biotherapy) within 30 days or 5 half-lives, whichever is shorter, prior to the date of C1D1; or need to continue these drugs during study participation.
• Has received treatment with inhibitors of P-glycoprotein (P-gp), or Breast Cancer Resistant Protein (BCRP), or Organic Anion Transporting Polypeptides 1B1/1B3 (OATP1B1/1B3) within 7 days prior to the date of C1D1. Has received treatment with inducers of P-gp within 14 days prior to the date of C1D1.
• Has received any live vaccine within 30 days prior to the date of C1D1.
• Has received any transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days prior to date of C1D1.
• Has a history within 12 months prior to screening of clinically significant or uncontrolled cardiac disease, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, or clinically significant arrhythmia not controlled by standard of care therapy.
• Has baseline Left Ventricular Ejection Fraction (LVEF) <50% or less than institutional lower limit of normal.
• Has clinically significant abnormal blood pressure according to investigator assessment, or inadequately treated and uncontrolled hypertension including history of hypertensive crisis; hypertensive encephalopathy; or adjustment of antihypertensive medications due to poor blood pressure control within 14 days prior to the date of C1D1.
• Has a history of nephrotic syndrome or Grade 3 proteinuria.
• Meets the following criteria for proteinuria during screening assessments: ≥2+ proteinuria on urine dipstick and 24-hour urine collection demonstrating ≥1 g of urine protein in 24 hours.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07684612 · 224040 · 2025-523366-24-00 · GOG- 3136 · ENGOT-ov99 · APGOT-OV19

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗