Dostarlimab and Cobolimab in Advanced Cervical Cancer

NCT06238635 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-560
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

This research is being done to determine how effective dostarlimab in combination with cobolimab is in metastatic or recurrent cervical cancer.

Conditions

Recurrent Cervical Carcinoma; Cervical Cancer; Advanced Cervical Carcinoma; Metastatic Cervical Cancer; Metastatic Cervical Carcinoma

Keywords

Cervical Cancer; Advanced Cervical Cancer; Advanced Cervical Carcinoma; Metastatic Cervical Cancer; Metastatic Cervical Carcinoma; Recurrent Cervical Cancer; Recurrent Cervical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) Based on irRECIST

  ORR based on irRECIST is defined as the proportion of participants who achieved partial response or complete response during study treatment based on immune-related RECIST criteria.

  Up to 2 years

Secondary Outcomes (4)

• Median Progression-Free Survival (PFS)

  Up to 3 years

• Median Overall Survival (OS)

  Up to 3 years

• Immune-Related (PFS) Progression-Free Survival

  Up to 7 years

• Grade 3-5 Adverse Events Rate

  Up to 2 years

Study Arms (2)

Cohort A: Immunotherapy Naive

EXPERIMENTAL

10 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day 1 of 21 Day cycle: Dostarlimab 1x daily and Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 19 additional participants will be enrolled.

Drug: Dostarlimab; Drug: Cobolimab

Cohort B: Immunotherapy Exposed

EXPERIMENTAL

14 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day of 21 Day cycle: Predetermined dose of Dostarlimab 1x daily. Predetermined dose of Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 23 additional participants will be enrolled.

Drug: Dostarlimab; Drug: Cobolimab

Interventions

Dostarlimab DRUG

Humanized monoclonal antibody, 50mg/mL type 1 borosilicate clear glass vial, via intravenous infusion per protocol.

Also known as: TSR-042, GSK4057190, C6420H9832N1680O2014S44

Cohort A: Immunotherapy Naive; Cohort B: Immunotherapy Exposed

Cobolimab DRUG

Humanized anti-TIM-3 monoclonal antibody, 20mg/mL single-use vial, via intravenous infusion per protocol.

Also known as: TSR-022, GSK4069889A

Cohort A: Immunotherapy Naive; Cohort B: Immunotherapy Exposed

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed cervical carcinoma, all histologies included.
• All patients must have measurable disease as defined by RECIST 1.1. as defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be \>10 mm when measured by CT, MRI or caliper measurement by clinical exam; or \>20 mm when measured by chest x-ray. Lymph nodes must be \>15 mm in the short axis when measured by CT or MRI. Radiological evaluation should occur within 30 days prior to enrollment initiation.
• Age of 18 or greater years. Because insufficient dosing or adverse event data are available on the use of dostarlimab or cobolimab in participants \<18 years of age, children are excluded from the study. Cervical cancer is rare in the pediatric population.
• ECOG performance status 0, 1, or 2.
• Availability of at least two formalin fixed paraffin embedded (FFPE) blocks of cancer tissue OR at least 1 FFPE block AND at least 3 unstained 5-micron slides, OR at least 1 unstained 5-micron slides from original surgery or biopsy or from a biopsy of recurrent disease.
• Participants must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,500/mcL
• platelets ≥100,000/mcL
• hemoglobin ≥ 9 g/dL
• total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) OR direct bilirubin ≤ 1.0 x ULN
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN unless liver metastases are present, in which case they must be ≤ 5.0 x ULN
• creatinine ≤ 1.5 x institutional ULN OR Glomerular filtration rate (GFR) ≥50 mL/min/1.73 m2 unless data exists supporting safe use at lower kidney function values, no lower than 30 mL/min/1.73 m2 (see Appendix B).
• INR or PT ≤ 1.5 x ULN unless the patient receives anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured (via sustained virologic response). For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the first dose of study medication.
• Participants who are receiving any other investigational agents.
• Patient has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable, have no evidence of new or enlarging brain metastases on repeat imaging at least 4 weeks after treatment, and are off steroids 3 days prior to dosing with study treatment. Stable brain metastases by this definition should be established prior to the first dose of study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dostarlimab or cobolimab. Known severe hypersensitivity reactions to monoclonal antibodies (Grade \>=3, NCI CTCAE 5.0).
• Participants with a history of treatment anti-CTLA4, TIM3 antagonist, or other investigational agents that target immune checkpoint inhibitors
• Participants who had prior anti-PD-1 or anti-PD-L1 therapy
• History of interstitial lung disease
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), that does not meet the following criteria: a. subject with HIV infection is eligible if undetectable HIV RNA within 4 weeks of study drug administration, b. absence of acquired immunodeficiency syndrome defining opportunistic infections within the past 12 months prior to study enrollment, and c. is on antiretroviral therapy for at least 4 weeks prior to study enrollment.
• Patient has known active hepatitis B (eg, hepatitis B surface antigen reactive) or hepatitis C (eg, positive hepatitis C antibody and hepatitis C virus ribonucleic acid qualitative is detected) or known active hepatic cirrhosis. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for hormone replacement and at doses of \<=5 mg or 5 mg equivalent prednisone per day.
• Uncontrolled current illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Intranasal, inhaled, topical steroids or local steroid injections (e.g. intra-articular injection);
• at physiologic doses not to exceed 5 mg/day prednisone or equivalent;
• Steroids at premedication for hypersensitivity reactions (e.g., CT scan premedication)

Sponsors & Collaborators

• GlaxoSmithKline: collaborator
• Meghan Shea: lead

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Meghan Shea, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: March 11, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 15, 2027
• Last Updated: January 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (2)