Surgery for Relapsed Ovarian Cancer in Precision

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Procedure: surgery/chemotherapy; Drug: Iparomlimab/Tuvonralimab

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tingyan Shi, MD, PHD; Phone Number: 86-21-64041990; Email: shi.tingyan@zs-hospital.sh.cn
• Study Contact Backup: Name: Yulian Chen, MD; Phone Number: 86-21-64041990; Email: emma_serendipity@163.com

Study Locations

• China
  • Shanghai, China
    • Zhongshan Hospital Fudan University
    • Contact: Tingyan Shi, MD, PHD; Email: shi.tingyan@zs-hospital.sh.cn
    • Principal Investigator: Rongyu Zang, MD, PHD
  • Wuhan, China
    • Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
    • Contact: Qinglei Gao, MD, PHD; Email: gingleigao@hotmiail.com
    • Principal Investigator: Qinglei Gao, MD,PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: real world arm; 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.
Experimental: criteria-fulfilled arm; 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.	Procedure: surgery/chemotherapy; secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy; Drug: 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.
Experimental: compassionate use arm; 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.	Procedure: surgery/chemotherapy; secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival in CF arm	The time from entry into the study to the diagnosis of the first progression or recurrence or death in CF arm, whichever occurs first	Up to 3 years
3-years Overall Survival Rate in CF arm	The proportion of patients without death at 3 years after entry into the study in CF arm	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival in CF arm	The time from entry into the study to the date of death from any cause or last follow-up in CF arm	Up to 3 years
TFST in CF arm	Time from entry into the study until the starting date of the first subsequent anticancer therapy or death, whichever occurred first, whichever occurred first, in CF arm	Up to 3 years
TSST in CF arm	Time from entry into the study until the starting date of the second subsequent anticancer therapy or death, whichever occurred first, in CF arm	Up to 3 years
Post-operative complications in CF and CU arms	The surgical complications will be evaluated at 30-day after secondary cytoreductive surgery in CF and CU arms	Up to 1 months
Quality of life assessments in CF arm using EORTC QLQ-C30	Changes in EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) scores in CF arm (baseline; 6 months, 12 months, 24 months and 36 months after entry into the study; score range 0-126; higher score = worse outcome)	Up to 3 years
Quality of life assessments in CF arm using FACT-O	Changes in FACT-O (Functional Assessment of Cancer Therapy-Ovarian cancer) scores in CF arm (baseline; 6 months, 12 months, 24 months and 36 months after entry into the study; score range 0-156; higher score = worse outcome)	Up to 3 years

Collaborators and Investigators

• Sponsor: Shanghai Gynecologic Oncology Group
• Collaborators: Shanghai Zhongshan Hospital; Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: September 9, 2024
• First Submitted That Met QC Criteria: September 15, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): June 27, 2025
• Last Update Submitted That Met QC Criteria: June 24, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Ovarian cancer; Biomarker-driven; Immune checkpoint inhibitor; Secondary cytoreduction
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Neoplasms, Glandular and Epithelial; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Carcinoma; Fallopian Tube Diseases; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms; Fallopian Tube Neoplasms
• Other Study ID Numbers: SOC-P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No