Dostarlimab + Cobolimab for Cervical Cancer

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Meghan Shea, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Meghan Shea

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Herbal products

Disqualifiers: Active CNS metastases, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use natural herbal products or other 'folk remedies' while participating in this study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the drug Dostarlimab + Cobolimab for cervical cancer?

Dostarlimab has shown promising results in treating endometrial cancer and has been approved for use in certain cases, with a 100% remission rate reported in a trial for rectal cancer. Although not directly related to cervical cancer, these results suggest potential effectiveness in other cancers.

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Is Dostarlimab safe for humans?

Dostarlimab has been approved for use in certain types of cancer, like endometrial cancer, based on its ability to shrink tumors. While it has shown promise, its safety continues to be monitored through ongoing trials to ensure it is safe for humans.

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How is the drug Dostarlimab + Cobolimab unique for treating cervical cancer?

Dostarlimab is a novel drug that works by blocking a protein called PD-1, which helps the immune system attack cancer cells. It has shown promising results in treating other cancers like endometrial and rectal cancer, and its combination with Cobolimab for cervical cancer could offer a new approach by potentially enhancing the immune response against the tumor.

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Eligibility Criteria

This trial is for adults with measurable, recurrent or metastatic cervical cancer. They must have good organ function and performance status, no severe prior treatment side effects, and not be pregnant or breastfeeding. Those previously treated for hepatitis C can join if cured. Exclusions include past immune checkpoint inhibitor therapy, recent chemo or radiotherapy, active autoimmune diseases, HIV/AIDS, current serious illnesses, use of immunosuppressants or live vaccines recently.

Inclusion Criteria

My cancer can be measured by standard health scans.

I am 18 years old or older.

My organs and bone marrow are functioning well.

Exclusion Criteria

I have never had any type of cancer other than my current diagnosis.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to dostarlimab or cobolimab

I have a history of lung scarring or fibrosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab and cobolimab daily in 21-day cycles for up to 2 years

Up to 2 years

Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment with imaging tests every 3 months for 2 years, then every 6 months for an additional 5 years

7 years

Every 3 months for 2 years, then every 6 months for 5 years

Participant Groups

The study tests the effectiveness of combining two drugs: Dostarlimab and Cobolimab in treating advanced cervical cancer that has spread (metastatic) or returned after treatment (recurrent). The goal is to see how well these drugs work together against this type of cancer.

Group I: Cohort B: Immunotherapy Exposed Experimental Treatment 2 Interventions

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.

Group II: Cohort A: Immunotherapy Naive Experimental Treatment 2 Interventions

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Dana-Farber Cancer Institute Boston, MA

Massachusetts General Hospital Cancer Center Boston, MA

Beth Israel Deaconess Medical Center Boston, MA

Who Is Running the Clinical Trial?

Meghan Shea Lead Sponsor

GlaxoSmithKline Industry Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. [2023] Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer.

2. United States pubmed.ncbi.nlm.nih.gov

Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. [2023] Balstilimab (antiprogrammed death-1) and zalifrelimab (anticytotoxic T-lymphocyte-associated antigen-4) are two new checkpoint inhibitors emerging as promising investigational agents for the treatment of advanced cervical cancer. This phase II trial (ClinicalTrials.gov identifier: NCT03495882) evaluated the combination of balstilimab plus zalifrelimab in patients with recurrent and/or metastatic cervical cancer who relapsed after prior platinum-based therapy.

3. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021] The use of monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, programmed cell death 1 ligand 1 (PD-L1), widely extends to a large number of tumors such as melanoma, non-small cell lung, renal or lymphomas, among others. Some of them are already approved as first- or second-line treatment, as pembrolizumab, nivolumab or cemiplimab. Dostarlimab is an investigational humanized anti-PD-1 that is being developed both in monotherapy and as combination therapy, for gynecological tumors but also for lung cancer or melanoma. The preliminary results, particularly in endometrial cancer, show a high affinity against PD-1 with encouraging clinical activity. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022] Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody for the treatment of adult patients, with mismatch repair deficient (dMMR), recurrent or advanced endometrial cancer that has progressed on or following prior therapy with a platinum-containing regimen. As determined by an FDA-approved test this indication was granted rapid approval based on the rate of tumor response and the duration of the response. Continued approval for this indication is conditioned on further confirmatory trials demonstrating and documenting clinical benefit. In June 2022, the clinical trial NCT04165772 reported a 100% remission rate for rectal cancer. This clinical trial brought proof that we can match a tumor and the genetics of what is driving it, with therapy. This clinical trial continues to enroll patient and is currently enrolling patients with gastric, prostate, and pancreatic cancers. Dostarlamib is being recommended for rectal cancer. The focus of this review is to summarize the existing knowledge regarding Dostarlimab and explore the possibilities of mono- and combination therapies.

5. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021] Dostarlimab (Jemperli™; GlaxoSmithKline) is a humanized monoclonal antibody programmed death-1 (PD-1) receptor antagonist being developed for the treatment of various cancers. Based on preliminary results from the GARNET trial dostarlimab has recently been approved in the EU and USA for the treatment of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer. This article summarizes the milestones in the development of dostarlimab leading to these first approvals.

6. United States pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023] The Food and Drug Administration (FDA) has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors.

7. United States pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. [2022] Three new drugs are presented: dostarlimab, loncastuximab tesirine, and aducanumab. Product information, clinical trials, and recommendations are provided. Dostarlimab (Jemperli®) is FDA-indicated for the treatment of adult patients with mismatch repair deficient (dMMR - an abnormality that affects DNA repair) recurrent or advanced endometrial cancer (EC). Loncastuximab tesirine (Zynlonta®) is FDA-indicated for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. Aducanumab (Aduhelm®) is FDA-indicated for the treatment of Alzheimer's disease. It is an amyloid beta-directed antibody developed by Biogen of Cambridge, Massachusetts. This indication was approved on June 7, 2021, under the accelerated approval based on the reduction in amyloid beta plaques in patients treated with the drug.

8. United States pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. [2023] Dostarlimab (JEMPERLI) is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody (mAb) which is approved by the US Food and Drug Administration for patients with recurrent/advanced mismatch repair-deficient solid tumors, including endometrial cancer, following progression on prior treatment, with approval based on data from the phase I GARNET trial. To support dostarlimab dose regimen recommendations, we estimated and compared the potency of dostarlimab relative to anti-PD-1 mAb pembrolizumab using both data published from the KEYNOTE-001 trial of pembrolizumab and data from the GARNET trial. PD-1 target engagement was assessed ex vivo in blood samples via a super antigen staphylococcal enterotoxin B stimulation assay and interleukin-2 (IL-2) stimulation ratios calculated for dostarlimab. A non-linear mixed-effect sigmoid maximum effect inhibitory model was fitted to dostarlimab IL-2 stimulation ratios using extracted pembrolizumab data as informative priors. The estimated half-maximal effective concentration was 1.95 μg ml-1 (95% credibility interval: 0.21-5.87) for dostarlimab and 1.59 μg ml-1 (95% confidence interval: 0.42-6.12) for pembrolizumab. These findings suggest dostarlimab and pembrolizumab to be equipotent for peripheral PD-1 suppression based on analysis of ex vivo IL-2 stimulation ratios. Accounting for a three-fold dilution between serum and tumor, a target dostarlimab trough concentration of ~54 μg ml-1 would be needed for 90% suppression in the tumor. These data support the use of dostarlimab as a potent PD-1 suppressor and the recommended dostarlimab monotherapy dose regimen of 500 mg Q3W ×4 cycles followed by 1000 mg Q6W thereafter in recurrent/advanced solid tumors.