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Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer

28 septembre 2026 mis à jour par: Peking University Cancer Hospital & Institute

Trastuzumab Rezetecan Plus Bevacizumab in Platinum-Sensitive Recurrent Ovarian Cancer: A Phase II, Multicenter, Single-Arm Study

This study is a prospective, multicenter, single-arm, open-label phase II clinical trial.

It is planned to enroll 53 subjects with HER2-expressing (IHC 1+, 2+, or 3+) partially platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (defined as disease recurrence occurring ≥6 months and <12 months after the completion of the last platinum-containing therapy).

The study adopts a two-stage sequential treatment strategy:

Stage 1: All enrolled subjects will receive Trastuzumab Rezetecan (4.8 mg/kg IV, Q3W) combined with Bevacizumab (7.5 mg/kg IV, Q3W). Trastuzumab Rezetecan will be administered for a maximum of 1 year, or until disease progression, unacceptable toxicity, or other protocol-defined discontinuation criteria are met, whichever occurs first; Bevacizumab will be continued until disease progression, unacceptable toxicity, or other protocol-defined reasons.

Stage 2: Upon confirmed disease progression in Stage 1, subjects will enter Stage 2 to receive platinum-based chemotherapy (e.g., Carboplatin + Paclitaxel, Carboplatin + Liposomal Doxorubicin, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may replace Carboplatin in cases of intolerance, including but not limited to these regimens, determined by the investigator) until subsequent disease progression or unacceptable toxicity.

The primary objective is to evaluate progression-free survival 1 (PFS1) of SHR-A1811 combined with bevacizumab based on RECIST v1.1. Secondary objectives include objective response rate (ORR), disease control rate (DCR), progression-free survival 2 (PFS2), overall survival (OS), and safety and tolerability.

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Estimé)

53

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Beijing Municipality
      • Beijing, Beijing Municipality, Chine, 100000
        • Peking University Cancer Hospital & Institute

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 75 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Femelle

La description

Inclusion Criteria:

  1. Voluntarily agree to participate in the study, provide written informed consent, demonstrate good compliance, and be able to cooperate with protocol-required follow-up visits.

  2. Female patients aged 18 to 75 years old (inclusive, calculated from the date of signing the informed consent form).

  3. Histologically or cytologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (mucinous carcinoma is excluded).

  4. Received 1 to 2 prior lines of systemic therapy and must have received prior PARP inhibitor therapy.

  5. Partially platinum-sensitive recurrence, defined as disease recurrence occurring ≥6 months but <12 months after the completion of the last platinum-containing therapy:

    • Neoadjuvant and/or adjuvant therapy are combined and counted as 1 line of therapy;
    • Maintenance therapy does not count as a separate line of therapy;
    • Changes in treatment regimens due to reasons other than disease progression (such as intolerable toxicity) are considered part of the same line of therapy and are not counted separately.
  6. Confirmed HER2 expression status: IHC 1+, 2+, or 3+.

  7. At least one measurable lesion according to RECIST v1.1 criteria (longest diameter ≥10 mm on spiral CT scan, or short axis ≥15 mm for lymph nodes).

  8. ECOG performance status (PS) score: 0 to 1..

  9. Expected life expectancy ≥12 weeks.

  10. Adequate function of vital organs.

Exclusion Criteria:

  1. Central nervous system (CNS) metastasis: Untreated or active CNS metastases. Subjects are eligible if CNS metastases have received adequate local therapy (e.g., surgery or radiotherapy), neurological symptoms have returned to baseline (excluding residual signs or symptoms related to CNS treatment), and clinical stability has been maintained for ≥ 4 weeks prior to the first dose.
  2. Second primary malignancy, except for the following: adequately treated basal cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of the breast, or papillary thyroid carcinoma; or other malignancies that have been adequately treated with curative intent and have shown no evidence of recurrence or metastasis for >= 2 years prior to the first dose.
  3. Uncontrolled pleural effusion or ascites. Subjects are eligible if therapeutic drainage has been performed and clinical stability has been maintained for at least 2 weeks after drainage.
  4. Severe pulmonary disease: History of interstitial lung disease (ILD) or non-infectious pneumonitis (such as radiation pneumonitis) requiring systemic corticosteroid therapy; current or suspected ILD, non-infectious pneumonitis, or other active pulmonary inflammation; or significant pulmonary impairment including severe asthma, severe chronic obstructive pulmonary disease (COPD), or restrictive lung disease within 6 months prior to the first dose.
  5. Tuberculosis infection: Active pulmonary tuberculosis infection. Subjects who have received adequate and standard anti-tuberculosis therapy and have discontinued anti-tuberculosis treatment for >= 3 months prior to the first dose are eligible.
  6. Uncontrolled cardiovascular disease: Poorly controlled or serious cardiovascular disease, including but not limited to unstable angina, symptomatic congestive heart failure (NYHA Class II-IV), acute myocardial infarction within 6 months prior to the first dose, or unstable arrhythmias requiring clinical intervention within 1 month prior to the first dose.
  7. High-risk gastrointestinal indications (perforation/fistula): Gastrointestinal perforation, gastrointestinal fistula, tracheoesophageal fistula, urethral fistula, or abdominal abscess occurring within 3 months prior to the first dose, or judged by the investigator to have a high risk of occurrence in the near future. Subjects who have undergone definitive treatments such as artificial stoma or ureteral stent placement and are evaluated by the investigator as clinically stable are eligible.
  8. Active infection: Severe infection occurring within 1 month prior to the first dose; any active infection requiring systemic intravenous antimicrobial therapy; or unexplained fever (> 38.5 deg C) from the screening period up to the first dose.
  9. Specific prior drug exposure: Prior treatment with antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, or prior single-agent topoisomerase I inhibitor therapy (such as irinotecan, topotecan).
  10. Drug hypersensitivity: Known hypersensitivity to any active ingredient or excipient of Trastuzumab Rezetecan (SHR-A1811), including the antibody, payload SHR169265, and linker; known hypersensitivity to any component of Bevacizumab, or a history of severe hypersensitivity reactions.
  11. Other comprehensive risks: Any clinical condition that, in the opinion of the investigator, may increase the risk to the subject, interfere with the interpretation of study results, or preclude compliance with the study protocol.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: N / A
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Sequential Treatment Group

Stage 1: SHR-A1811 (4.8 mg/kg, IV) + Bevacizumab (7.5 mg/kg, IV), Q3W, until disease progression or intolerable toxicity. Stage 2: Upon confirmed progression in Stage 1, subjects proceed to receive investigator's choice of platinum-based chemotherapy rechallenge until subsequent progression or intolerable toxicity.

Humanized anti-HER2 IgG1 monoclonal antibody conjugated with a topoisomerase I inhibitor payload (SHR169265). Administered IV at 4.8 mg/kg on Day 1 of each 21-day cycle.

Recombinant humanized anti-VEGF monoclonal antibody. Administered IV at 7.5 mg/kg on Day 1 of each 21-day cycle (dosing interval >30 min after SHR-A1811).

Platinum-based chemotherapy rechallenge administered in Stage 2, selected by the investigator based on patient clinical condition (including but not limited to: Carboplatin + Paclitaxel ± Bevacizumab, Carboplatin + Pegylated Liposomal Doxorubicin ± Bevacizumab, or Carboplatin + Gemcitabine ± Bevacizumab; Cisplatin or Nedaplatin may be substituted if carboplatin is not tolerated).

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
PFS1
Délai: From the first dose of study treatment up to approximately 36 months.

Progression-Free Survival 1 (PFS1) as assessed by the investigator based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Defined as the time from the date of the first dose of study treatment to the date of first documented objective tumor progression or death due to any cause, whichever occurs first.

From the first dose of study treatment up to approximately 36 months.

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Objective Response Rate (ORR)
Délai: Up to approximately 36 months.

Defined as the proportion of subjects who achieve a Best Overall Response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) based on RECIST v1.1 criteria.

Up to approximately 36 months.
Disease Control Rate (DCR)
Délai: Up to approximately 36 months.

Defined as the proportion of subjects who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) based on RECIST v1.1 criteria.

Up to approximately 36 months.
Progression-Free Survival 2 (PFS2)
Délai: Up to approximately 36 months.

Defined as the time from the date of the first dose of study treatment in Stage 1 to the second documented objective disease progression or death due to any cause, whichever occurs first.

Up to approximately 36 months.
Overall Survival (OS)
Délai: Up to approximately 36 months.

Defined as the time from the date of the first dose of study treatment to death due to any cause, calculated in the intent-to-treat (ITT) population.

Up to approximately 36 months.
Safety and Tolerability
Délai: From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).

Incidence, severity, and causality of adverse events (AEs) and serious adverse events (SAEs) graded according to NCI-CTCAE v5.0 criteria, as well as the proportion of dose interruptions, dose reductions, and treatment discontinuations due to treatment-related toxicities.

From signing the informed consent form up to 30 days after the last dose of study treatment (and up to 90 days after the last dose of bevacizumab).

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Estimé)

22 octobre 2026

Achèvement primaire (Estimé)

30 septembre 2028

Achèvement de l'étude (Estimé)

30 septembre 2029

Dates d'inscription aux études

Première soumission

20 septembre 2026

Première soumission répondant aux critères de contrôle qualité

20 septembre 2026

Première publication (Réel)

28 septembre 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

1 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 septembre 2026

Dernière vérification

1 septembre 2026

Plus d'information

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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