GSK6097608 + Dostarlimab for Advanced Cancers

Not currently recruiting at 11 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with advanced solid tumors, such as non-small-cell lung cancer, head and neck cancer, and colorectal cancer, particularly those who have not responded to standard treatments. Researchers test different drug combinations to assess their safety and effectiveness, including GSK6097608 (Nelistotug), dostarlimab, cobolimab, and belrestotug. Participants will receive these drugs in various combinations to identify the best approach. Individuals with solid tumors that have worsened after conventional treatments might be suitable for this study. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive potentially groundbreaking therapies.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dostarlimab, a drug in this clinical trial, has been generally well-tolerated in past studies. It demonstrated quick and lasting effects against tumors with few side effects when used alone. When combined with other drugs like belrestotug and cobolimab, dostarlimab improved results in certain cancers, such as non-small cell lung cancer (NSCLC) and melanoma. These combinations have been studied without major safety concerns.

GSK6097608 is another drug tested in this trial for advanced solid tumors and NSCLC. Early findings suggest it is generally safe for humans, but more safety data is needed as it remains in the early stages of testing.

Overall, while dostarlimab has a strong safety record, GSK6097608 is still under evaluation. Participants considering this trial can find some reassurance in the positive safety data available, especially for dostarlimab. However, as with any early-stage trial, unknowns remain about the full safety of the new drug combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they involve innovative combinations of drugs that might offer new hope for advanced cancer patients. Unlike the standard chemotherapy options, which can attack both cancerous and healthy cells, these treatments utilize immunotherapy agents like dostarlimab and cobolimab, which aim to boost the body's own immune system to specifically target and fight cancer cells. One standout feature is the use of GSK6097608, a novel compound being tested both alone and in combination with other drugs, potentially offering a unique mechanism of action that could lead to better outcomes. The combination strategies being explored, like dostarlimab with belrestotug and GSK6097608, are designed to enhance the immune response, making them distinct from more traditional therapies by possibly reducing side effects and improving efficacy.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that dostarlimab, one of the treatments in this trial, can effectively treat some advanced cancers, particularly endometrial cancer, when used alone. It blocks a protein that helps cancer cells evade the immune system. In this trial, participants may receive dostarlimab alone or with other drugs. Combining dostarlimab with belrestotug, as in one of the trial arms, improved responses in patients with a type of lung cancer that cannot be surgically removed, although overall benefits vary. Another trial arm combines dostarlimab with cobolimab, which showed better results in treating high-risk melanoma that can be surgically removed, compared to dostarlimab alone. GSK6097608, another treatment option in this trial, is a newer experimental drug with limited information available, but researchers are studying its potential to treat advanced solid tumors. The goal of combining these drugs in the various trial arms is to enhance the immune system's ability to fight cancer, although more data on GSK6097608 is still being gathered. ^{5 6 7 8 9}

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 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 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]

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, 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 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-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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2216334

Dostarlimab for Primary Advanced or Recurrent ... Dostarlimab plus carboplatin–paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer.

2. onclive.com onclive.com/view/real-world-analysis-confirms-efficacy-safety-of-dostarlimab-plus-chemotherapy-in-advanced-endometrial-cancer

Real-World Analysis Confirms Efficacy/Safety of ... Findings from a real-world study confirm the efficacy and safety of dostarlimab plus chemotherapy in advanced endometrial cancer.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40616648/

Efficacy of dostarlimab in recurrent or advanced mismatch ... Conclusion: Dostarlimab demonstrated limited efficacy in patients with pMMR EC, but it represented better outcomes in those with dMMR EC.

4. jemperlihcp.com jemperlihcp.com/efficacy/garnet-trial/

GARNET Efficacy & Study Design - Jemperli View study design and results for the GARNET trial, including key inclusion and exclusion criteria. See full Indication, Safety, & Prescribing Info.

5. gsk.com gsk.com/en-gb/media/press-releases/jemperli-dostarlimab-trial-continues-to-show-unprecedented-results/

Jemperli (dostarlimab) trial continues to show ... GSK is advancing studies evaluating dostarlimab in patients with advanced/metastatic stages of dMMR/MSI-H colorectal cancer through its AZUR ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39346117/

Safety of dostarlimab in combination with chemotherapy ... Dostarlimab, an immune checkpoint inhibitor, is being tested to treat many types of cancer, including endometrial cancer. In the RUBY trial, a ...

7. jemperlihcp.com jemperlihcp.com/

Primary Advanced or Recurrent Endometrial Cancer Treatment Discover JEMPERLI (dostarlimab-gxly) + CP, an IO-based treatment for primary advanced or recurrent endometrial cancer. See full Indication, Safety, & PI.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0090825824011727

Efficacy and safety of dostarlimab in combination with ... Dostarlimab+chemotherapy showed a statistically significant PFS benefit in patients with dMMR/MSI-H endometrial cancer (EC).

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02715284

NCT02715284 | Study of TSR-042, an Anti-programmed ... Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ ...