Surgery for Relapsed Ovarian Cancer in Precision

Официальное название

Surgery With ICBs in BRCAwt, CD8+ TILs, 1st Relapsed Ovarian Cancer: A Pilot Study

Обзор

This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with anti-PD1/CTLA-4 bispecifics therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC).

Подробное описание

The immune phenotype of patients with relapsed ovarian cancer may correlate with their response to immunotherapy. This multicenter, biomarker-driven, patient-centric study aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with anti-PD1/CTLA-4 bispecifics therapy in patients with platinum-sensitive relapsed ovarian cancer (PSROC). PD-L1 expression and CD8+ tumor-infiltrating T cell count (CD8+ TILs count) were evaluated as biomarkers using archived or fresh tumor tissue samples in patients with BRCA1/2 wild type.

This study would be proceeded in two phases. The phase 1b single-arm study aimed to evaluate the efficacy of Iparomlimab/tuvonralimab in the treatment of BRCA wild type, PD-L1-positive, CD8+ TILs-positive, patients with PSROC. The patent-centric phase II study with three arms aimed to evaluate the efficacy of secondary cytoreduction followed by platinum-based chemotherapy in combination with Iparomlimab/tuvonralimab in these patients. In arm 1 and 2, patients received secondary cytoreduction followed by platinum-based chemotherapy in combination with Iparomlimab/tuvonralimab. In arm 3, patients received physician's therapy of choice.

Вмешательства

• Процедура surgery/chemotherapy
  secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy
• Препарат Iparomlimab/Tuvonralimab
  Iparomlimab/tuvonralimab will be administered at a dose of 5 mg per kilogram IV every 21 days. Treatment will continue until disease progression confirmed by RECIST criteria v1.1, intolerable toxicity or withdrawal of consent.

Первичные конечные точки

• Progression-free survival in CF arm [Срок оценки: Up to 3 years]
• 3-years Overall Survival Rate in CF arm [Срок оценки: Up to 3 years]

Вторичные конечные точки (6)

• Overall survival in CF arm [Срок оценки: Up to 3 years]
• TFST in CF arm [Срок оценки: Up to 3 years]
• TSST in CF arm [Срок оценки: Up to 3 years]
• Post-operative complications in CF and CU arms [Срок оценки: Up to 1 months]
• Quality of life assessments in CF arm using EORTC QLQ-C30 [Срок оценки: Up to 3 years]
• Quality of life assessments in CF arm using FACT-O [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• Arm 1 (criteria-fulfilled, CF)

• Age at recurrence ≥ 18 years, <80 years.
• Patients with platinum-sensitive, first relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer (EOC, PPC, FTC), which is defined as those with treatment -free interval of 6 months or more.
• If the patient had previous PARPi maintenance therapy, disease progression should occurring at lease 3 months after the prior PARPi withdrawal.
• BRCA1/2 wild type (both germline and somatic)
• Homologous Recombination Deficiency (HRD) is available
• Patients must provide archived or fresh tumor tissue samples for biomarker detection.
• PD-L1 positive (if either at least 1% of assessed tumour cells expressed membranous PD-L1, at least 5% of immune cells within the tumour area expressed PD-L1, or both) and number of intraepithelial CD8+ tumor-infiltrating lymphocytes (TILs) per high-powered field ≥ 6.
• Assessed by the experienced surgeons, complete resection of all recurrent disease is possible (predicted by iMODEL score or by PET/CT).
• ECOG performance status of 0 to 2
• Adequate bone marrow, liver, and renal function to receive combined immunotherapy
• Written informed consent
• Arm 2 (compassionate use, CU), Similar to cohort 1, except for:

• If the patient had previous PARPi maintenance therapy, disease progression should occurring within 3 months after the prior PARPi withdrawal or during the PARPi maintenance therapy.
• PD-L1 positive or number of intraepithelial CD8+ TILs per high-powered field ≥ 6.
• Arm 3 (real word) Patients who meet the inclusion criteria but refuse to participate in the phase II CF and CU cohorts.

Критерии исключения

• Patients with borderline, low-grade tumors, clear cell carcinoma, as well as non-epithelial tumors.
• Patients with platinum-resistant or refractory diseases.
• Lack of tumor samples (archived and/or recently obtained) for biomarker detection.
• Previous administration of immunotherapy
• Patients have been vaccinated with the live vaccine or received anti-tumor treatment within 4 weeks before the first administration.
• Synchronous or metachronous (within 5 years) malignancy, symptomatic or uncontrolled visceral metastases that require simultaneous treatment, other than carcinoma in situ or breast cancer (without any signs of relapse or activity).
• Patients with parenchymal metastases and life-threatening complications in short term.
• Any other concurrent medical conditions contraindicating surgery, chemotherapy, or immunotherapy that could compromise the adherence to the protocol.
• Patients are known to be allergic to the active ingredients or excipients of Sintilimab.
• HRD status is not available.
• Any medication induced considerable risk of surgery, e.g. estimated bleeding due to oral anticoagulating agents or bevacizumab.
• Patients for interval-debulking, or for second-look surgery, or palliative surgery planned.
• Impossible to assess the resectability of recurrent disease or evaluate the score. Radiological signs suggesting complete resection is impossible.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Zhongshan Hospital Fudan University — Шанхай
• Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT06602063 · SOC-P

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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