Novel Immunotherapy Combinations for Head and Neck Cancer

Recruiting at 126 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Previous malignancies, Active tumor bleeding, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 24 months

360 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of the study is to evaluate the antitumor activity and safety of novel immunotherapy combinations compared with dostarlimab in participants with Programmed death ligand 1 (PD-L1) positive Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination for head and neck cancer?

Dostarlimab, a component of the treatment, has shown effectiveness in treating certain types of cancer by enhancing the immune system's ability to fight tumors. It has been approved for use in endometrial cancer and has shown promising results in other cancers, suggesting potential benefits for head and neck cancer as well. ^{1 2 3 4 5}

Is dostarlimab safe for humans?

Dostarlimab has been approved by the FDA for certain types of cancer, and studies have shown it to be well tolerated in animal models and humans. Clinical trials have demonstrated its safety, with no major safety concerns reported for its use in treating cancers like endometrial cancer. ^{1 2 3 4 5}

What makes the drug combination of Belrestotug, Dostarlimab, and GSK6097608 unique for head and neck cancer?

This drug combination is unique because it includes Dostarlimab, a PD-1 monoclonal antibody that enhances the immune system's ability to fight cancer by blocking a pathway that tumors use to hide from immune cells. Dostarlimab has shown promising results in other cancers, such as endometrial cancer, and its use in combination with other drugs for head and neck cancer could offer a novel approach to treatment. ^{1 2 3 4 5}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for adults with PD-L1 positive recurrent or metastatic squamous cell carcinoma of the head and neck, who haven't had systemic therapy in this setting. They must have a performance status that allows daily living activities (ECOG PS 0-1), measurable disease, and provide a recent tumor sample. Excluded are those with prior immune checkpoint inhibitor treatment, certain other cancers within the last 2 years, high bleeding risk tumors, recent progression after curative treatment, CNS metastases or active autoimmune diseases.

Inclusion Criteria

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

I haven't had systemic therapy for recurrent/metastatic disease, but may have had chemoradiation over 6 months ago.

I can provide a recent or stored tissue sample from my cancer, not just cells.

Exclusion Criteria

My cancer progressed within 4 months after treatment aimed at curing it.

I had cancer before, but it's been in complete remission for over 2 years and I don't need treatment now.

I have previously been treated with drugs that boost the immune system to fight cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive novel immunotherapy combinations or dostarlimab monotherapy

Up to approximately 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Belrestotug
• Dostarlimab
• GSK6097608

Trial Overview The study tests new immunotherapy combinations against dostarlimab to see which is better at fighting cancer in patients with specific head and neck cancers. Participants will be randomly assigned to receive either one of the novel treatments like Belrestotug or GSK6097608 or the known drug dostarlimab.

Participant Groups

Group I: Sub study 4: Dostarlimab and GSK4381562 Experimental Treatment 2 Interventions

Group II: Sub study 3: Dosarlimab and Belrestotug and nelistotug Experimental Treatment 3 Interventions

Group III: Sub study 2: Dostarlimab and nelistotug Experimental Treatment 2 Interventions

Group IV: Sub study 1: Dostarlimab and Belrestotug Experimental Treatment 2 Interventions

Group V: Dostarlimab Monotherapy Experimental Treatment 1 Intervention

Belrestotug is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer

Approved in United States as Jemperli for:

• Mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer
• Mismatch repair deficient (dMMR) recurrent or advanced solid tumors

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+

Findings from Research

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, a humanized anti-PD-1 antibody, has shown significant antitumor activity in humanized mouse models by enhancing T-cell functions and increasing immune cell infiltration, indicating its potential effectiveness in cancer treatment.

In clinical trials, dostarlimab was well tolerated and received FDA approval for treating adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer, demonstrating its safety and efficacy in a specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. Kumar, S., Ghosh, S., Sharma, G., et al.[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 (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, 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]

References

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

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

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

Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. [2022]

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

Dostarlimab: First Approval. [2021]

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

Dostarlimab: A Review. [2022]

5. 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]