Related Experiment Video
Updated: Sep 17, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Nivolumab and Ipilimumab Combination Treatment in Advanced Ovarian and Endometrial Clear Cell Cancers: A
Bo Gao1, Matteo S Carlino1,2, Michael Michael3
1Department of Medical Oncology, Blacktown and Westmead Hospitals, Sydney, Australia.
Importance:
Gynecological clear cell cancers (CCCs) are aggressive malignant neoplasms with low response rate to chemotherapy. The treatment of patients with metastatic disease remains an area of significant unmet need.
Objective:
To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade using nivolumab and ipilimumab in advanced gynecological CCCs.
Design, Setting, And Participants:
The MoST-CIRCUIT prospective multicenter phase 2 nonrandomized clinical trial included patients with advanced selected rare cancers. Patients with advanced clear cell ovarian cancer (CCOC)/clear cell endometrial cancer (CCEC) with a maximum of 1 course of prior systemic therapy were enrolled from August 2021 to February 2024 across 17 Australian and New Zealand sites.
Interventions:
Patients received nivolumab, 3 mg/kg, and ipilimumab, 1 mg/kg, every 3 weeks for 4 doses followed by nivolumab, 480 mg, every 4 weeks for 96 weeks until disease progression or the development of unacceptable toxic effects.
Main Outcomes And Measures:
Coprimary end points were objective response rate (ORR) and 6-month progression-free survival (PFS) as assessed by RECIST version 1.1 criteria, with the secondary end points being median overall survival, PFS, and treatment-related toxic effects.
Results:
Of 28 included patients, the median (range) age was 55 (34-77) years. A total of 24 had CCOC and 4 had CCEC; 19 (68%) had a previous course of therapy. Overall ORR was 54% (95% CI, 35-71), with 3 (12%) with complete response and 12 (42%) with partial response; the ORR was 55% (95% CI, 35-73) in the CCOC group and 50% (95% CI, 9-91) in the CCEC group. The median duration of response has not been reached, with all responses ongoing. The 6-month PFS was 58% (95% CI, 39-74), and the median overall survival has not been reached. A total of 9 patients (35%) experienced a grade 3 or 4 immune-related adverse event, and a grade 5 myocarditis occurred in 1 patient.
Conclusions And Relevance:
In this nonrandomized clinical trial, immunotherapy using combined anti-PD-1/CTLA-4 blockade demonstrated encouraging activity with a high rate of durable responses in patients with advanced gynecological CCCs. This regimen should be further investigated in this patient population with unmet medical need.
Trial Registration:
ClinicalTrials.gov Identifier: NCT04969887.
Insights
Immunotherapy with combined anti-PD-1/CTLA-4 blockade shows promising results for advanced gynecological clear cell cancers (CCCs). This treatment offers durable responses in patients with unmet medical needs.
Area of Science:
- Oncology
- Immunotherapy
- Gynecologic Oncology
Background:
- Gynecological clear cell cancers (CCCs) are aggressive and respond poorly to chemotherapy.
- Metastatic disease presents a significant unmet need in CCC treatment.
Purpose of the Study:
- To evaluate the efficacy of combined anti-programmed cell death 1 protein (PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) blockade in advanced gynecological CCCs.
- To assess the safety and efficacy of nivolumab and ipilimumab in this patient population.
Main Methods:
- A prospective, multicenter, nonrandomized phase 2 clinical trial (MoST-CIRCUIT).
- Patients with advanced clear cell ovarian cancer (CCOC) or clear cell endometrial cancer (CCEC) received nivolumab and ipilimumab.
- Treatment involved 4 doses every 3 weeks, followed by nivolumab every 4 weeks for 96 weeks or until progression.
Main Results:
- An objective response rate (ORR) of 54% was observed (3% complete response, 42% partial response).
- The 6-month progression-free survival (PFS) was 58%.
- Grade 3 or 4 immune-related adverse events occurred in 35% of patients; one grade 5 myocarditis was reported.
Conclusions:
- Combined anti-PD-1/CTLA-4 blockade demonstrates encouraging activity and durable responses in advanced gynecological CCCs.
- This immunotherapy regimen warrants further investigation for patients with this rare and aggressive cancer.
More Related Videos
Related Concept Videos
02:56Treatment Resistant Cancers
01:27Tumor Immunotherapy
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:11Clinical Trials: Overview