Surgery for Relapsed Ovarian Cancer in Precision

Shanghai Gynecologic Oncology Group

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma; Fallopian Tube Cancer

Treatments: Drug: Iparomlimab/Tuvonralimab; Procedure: surgery/chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06602063

SOC-P

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 33 estimated patients

Sex: Female

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Arm 1 (criteria-fulfilled, CF)

  1. Age at recurrence ≥ 18 years, <80 years.
  2. 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.
  3. If the patient had previous PARPi maintenance therapy, disease progression should occurring at lease 3 months after the prior PARPi withdrawal.
  4. BRCA1/2 wild type (both germline and somatic)
  5. Homologous Recombination Deficiency (HRD) is available
  6. Patients must provide archived or fresh tumor tissue samples for biomarker detection.
  7. 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.
  8. Assessed by the experienced surgeons, complete resection of all recurrent disease is possible (predicted by iMODEL score or by PET/CT).
  9. ECOG performance status of 0 to 2
  10. Adequate bone marrow, liver, and renal function to receive combined immunotherapy
  11. Written informed consent

• Arm 2 (compassionate use, CU), Similar to cohort 1, except for:

  1. 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.
  2. 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.

Exclusion criteria

1. Patients with borderline, low-grade tumors, clear cell carcinoma, as well as non-epithelial tumors.
2. Patients with platinum-resistant or refractory diseases.
3. Lack of tumor samples (archived and/or recently obtained) for biomarker detection.
4. Previous administration of immunotherapy
5. Patients have been vaccinated with the live vaccine or received anti-tumor treatment within 4 weeks before the first administration.
6. 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).
7. Patients with parenchymal metastases and life-threatening complications in short term.
8. Any other concurrent medical conditions contraindicating surgery, chemotherapy, or immunotherapy that could compromise the adherence to the protocol.
9. Patients are known to be allergic to the active ingredients or excipients of Sintilimab.
10. HRD status is not available.
11. Any medication induced considerable risk of surgery, e.g. estimated bleeding due to oral anticoagulating agents or bevacizumab.
12. Patients for interval-debulking, or for second-look surgery, or palliative surgery planned.
13. Impossible to assess the resectability of recurrent disease or evaluate the score. Radiological signs suggesting complete resection is impossible.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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33 participants in 3 patient groups

criteria-fulfilled arm

Experimental group

Description:

Patients who meet the inclusion and exclusion criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.

Treatment:

Procedure: surgery/chemotherapy

Drug: Iparomlimab/Tuvonralimab

compassionate use arm

Experimental group

Description:

Patients who are enrolled under expanded eligibility criteria will receive secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy with Iparomlimab/tuvonralimab maintenance therapy.

Treatment:

Procedure: surgery/chemotherapy

Drug: Iparomlimab/Tuvonralimab

real world arm

No Intervention group

Description:

Patients who meet the inclusion and exclusion criteria but refuse to participate in the CF and CU arms will receive the physician's therapy of choice.