Epithelial Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
Conditions
Keywords
Ovarian cancer, Immune checkpoint inhibitor, Secondary cytoreduction, Biomarker-driven
Brief summary
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).
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.
Interventions
PROCEDUREsurgery/chemotherapy
secondary cytoreductive surgery followed by 6 cycles of post-operative chemotherapy
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.
Sponsors
Shanghai Zhongshan Hospital
Tongji Hospital
Shanghai Gynecologic Oncology Group
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival in CF arm | Up to 3 years | The time from entry into the study to the diagnosis of the first progression or recurrence or death in CF arm, whichever occurs first |
| 3-years Overall Survival Rate in CF arm | Up to 3 years | The proportion of patients without death at 3 years after entry into the study in CF arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TSST in CF arm | Up to 3 years | Time from entry into the study until the starting date of the second subsequent anticancer therapy or death, whichever occurred first, in CF arm |
| Post-operative complications in CF and CU arms | Up to 1 months | The surgical complications will be evaluated at 30-day after secondary cytoreductive surgery in CF and CU arms |
| Overall survival in CF arm | Up to 3 years | The time from entry into the study to the date of death from any cause or last follow-up in CF arm |
| Quality of life assessments in CF arm using FACT-O | Up to 3 years | 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) |
| Quality of life assessments in CF arm using EORTC QLQ-C30 | Up to 3 years | 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) |
| TFST in CF arm | Up to 3 years | 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 |
Countries
China
Contacts
Primary ContactTingyan Shi, MD, PHD
Backup ContactYulian Chen, MD
Outcome results
None listed