GSK6097608 + Dostarlimab for Advanced Cancers

Recruiting at 10 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: GlaxoSmithKline

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Active infection, Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: Every 3 weeks

107 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drugs alone or in combination to treat people with advanced solid tumors. The drugs either attack cancer cells directly or help the immune system fight cancer. The study includes Japanese and Chinese participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had any prior anti-cancer treatment within 4 weeks or 5 half-lives of the drug, whichever is shorter.

Will I have to stop taking my current medications?

The trial requires that you stop any prior anti-cancer treatments at least 4 weeks before starting the study. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

Is the combination of GSK6097608 and Dostarlimab safe for humans?

Dostarlimab, also known as Jemperli, has been approved for use in certain types of advanced cancers, and its safety has been evaluated in clinical trials for various conditions. While specific safety data for the combination with GSK6097608 is not provided, Dostarlimab has been generally considered safe in humans for approved uses. ^{1 2 3 4 5}

Is the combination of GSK6097608 and Dostarlimab safe for humans?

Dostarlimab, also known as Jemperli, has been approved for use in certain cancers, indicating it has undergone safety evaluations. It has been tested in various trials, including for endometrial cancer and non-small cell lung cancer, showing it is generally safe for human use. ^{1 2 3 4 6}

What makes the drug combination of GSK6097608 and Dostarlimab unique for treating advanced cancers?

This drug combination is unique because it includes Dostarlimab, a monoclonal antibody that targets the PD-1 receptor, which is involved in the immune system's ability to fight cancer. Dostarlimab has shown promising results in treating various cancers, including endometrial cancer, by enhancing the body's immune response against tumors. ^{1 2 3 5 6}

What makes the drug combination of GSK6097608 and Dostarlimab unique for treating advanced cancers?

This drug combination is unique because it includes Dostarlimab, a monoclonal antibody that targets the PD-1 receptor, which is involved in the immune system's ability to fight cancer. Dostarlimab has shown promising results in treating mismatch repair deficient cancers, such as endometrial cancer, and is being explored for other solid tumors, making it a novel option for advanced cancers. ^{1 2 3 5 6}

What data supports the effectiveness of the drug combination GSK6097608 and Dostarlimab for advanced cancers?

Dostarlimab, one of the drugs in the combination, has shown effectiveness in treating certain advanced cancers, like endometrial cancer, by blocking a protein that helps cancer cells hide from the immune system. It has been approved for use in the US and EU based on its ability to shrink tumors and maintain that response. ^{1 2 3 5 7}

What data supports the effectiveness of the drug combination GSK6097608 and Dostarlimab for advanced cancers?

Dostarlimab has shown effectiveness in treating certain advanced cancers, such as endometrial cancer, by blocking a protein that helps cancer cells hide from the immune system. It has been approved for use in patients with specific genetic markers, and studies suggest it is as effective as another similar drug, pembrolizumab, in suppressing cancer-related proteins. ^{1 2 3 5 7}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who've tried standard treatments without success or can't tolerate them. They must be in good physical condition, have proper organ function, and for certain arms of the trial, provide fresh tumor biopsies. Women able to have children must use effective birth control. Exclusions include uncontrolled brain metastases, recent cancers besides the one being treated, active autoimmune diseases requiring treatment within 2 years, liver disease, infections like HIV/HBV/HCV, heart risks including QT prolongation on ECG.

Inclusion Criteria

Adequate cardiac ejection fraction as measured by echocardiogram

I am fully active or restricted in physically strenuous activity but can do light work.

Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only: is of Chinese descent and lives in China

Exclusion Criteria

You have a history of drug or alcohol abuse.

I have had a bone marrow or organ transplant.

I haven't had cancer treatment or experimental drugs in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of GSK6097608 as monotherapy and in combination with dostarlimab, belrestotug, and cobolimab in various arms

Every 3 weeks

IV infusions every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cobolimab
• Dostarlimab
• GSK4428859A (EOS884448)
• GSK6097608

Trial Overview The study tests GSK6097608 alone and combined with dostarlimab against various solid tumors. Dostarlimab is also tested alone and with belrestotug or cobolimab in specific participant groups from Japan and China. The goal is to assess safety and effectiveness while monitoring how the body processes these drugs (pharmacokinetics) and their impact on the body (pharmacodynamics).

How Is the Trial Designed?

Group I: Participants receiving dostarlimab plus cobolimab (Arm G) Experimental Treatment 2 Interventions

Participants will be administered an IV infusion of cobolimab followed by dostarlimab

Group II: Participants receiving dostarlimab plus belrestotug plus GSK6097608 (Arm F) Experimental Treatment 3 Interventions

Participants will be administered an IV infusion of dostarlimab followed by belrestotug followed by GSK6097608 every 3 weeks.

Group III: Participants receiving dostarlimab plus belrestotug (Arm E) Experimental Treatment 2 Interventions

Participants will be administered IV infusions of dostarlimab followed by belrestotug, every 3 weeks.

Group IV: Participants receiving dostarlimab monotherapy (Arm D) Experimental Treatment 1 Intervention

Participants will be administered an IV infusion of dostarlimab monotherapy (1 cohort will receive dostarlimab every 3 weeks and 1 cohort will receive dostarlimab every 6 weeks).

Group V: Participants receiving GSK6097608 plus dostarlimab (Arm B) Experimental Treatment 2 Interventions

Participants will be administered IV infusion of GSK6097608 every 3 weeks in escalating doses followed by dostarlimab.

Group VI: Participants receiving GSK6097608 monotherapy (Arm A) Experimental Treatment 1 Intervention

Participants will be administered an intravenous (IV) infusion of GSK6097608 every 3 weeks as monotherapy in escalating doses.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

iTeos Therapeutics

Industry Sponsor

Trials

11

Recruited

2,500+

23andMe, Inc.

Industry Sponsor

Trials

10

Recruited

83,700+

Published Research Related to This Trial

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

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. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab is approved for treating advanced endometrial cancer in patients with mismatch repair deficiency, highlighting its targeted approach to a specific genetic abnormality.

Aducanumab is indicated for Alzheimer's disease and received accelerated approval based on its ability to reduce amyloid beta plaques, although its clinical efficacy remains a topic of debate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. Gettman, L.[2022]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

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

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. [2023]

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

Dostarlimab: First Approval. [2021]

4. 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]

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

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

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

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]