Novel Immunotherapy Combinations for Head and Neck Cancer

Recruiting at 151 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

316 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drug combinations to evaluate their effectiveness against head and neck cancer that has spread or recurred, specifically in patients whose cancer cells express the protein PD-L1. It compares several experimental treatments, including dostarlimab (an immunotherapy drug), either alone or combined with other drugs like belrestotug. The goal is to determine which combination is the safest and most effective in shrinking tumors. Suitable candidates have head and neck cancer that cannot be cured with local treatments, affecting areas such as the mouth or throat, and have not received certain previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

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

A previous study showed that dostarlimab achieved 100% remission in advanced rectal cancer without significant side effects, suggesting it might be well-tolerated. Researchers are also testing dostarlimab with other drugs like belrestotug and nelistotug. In one study, combining belrestotug with dostarlimab improved the response rate in lung cancer, and no specific safety issues were reported. However, another study halted the development of belrestotug due to mixed results in a different type of cancer. Nelistotug is still early in testing, and its safety is under review. There is no specific safety data for dostarlimab combined with remzistotug, but dostarlimab alone has generally been well-tolerated. As this is a Phase 2 trial, the safety of these drug combinations is still being evaluated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they explore innovative combinations of immunotherapy drugs like Dostarlimab, Belrestotug, and others. Unlike traditional treatments such as surgery, radiation, and chemotherapy, which often have broad and harsh effects, these investigational drugs are designed to enhance the body's own immune response against cancer cells. Dostarlimab, for instance, is a checkpoint inhibitor that blocks specific proteins to help immune cells better recognize and attack cancer. Combining these with other novel agents like Belrestotug aims to further boost effectiveness and potentially reduce side effects, providing hope for more targeted cancer therapy.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research shows that dostarlimab, a treatment in this trial, can help the immune system fight certain cancers. It has shown promise in studies on head and neck cancer. In this trial, some participants will receive dostarlimab alone, while others will receive it in combination with other drugs. When combined with belrestotug, another treatment option in this trial, patients responded better than with dostarlimab alone. However, belrestotug did not work in a different cancer study, leading to its development being stopped. Researchers are now testing whether adding two other drugs, nelistotug and remzistotug, to dostarlimab can enhance its effects against tumors. Early results are hopeful, but more research is needed to confirm these benefits. ^{2 3 6 7 8}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Sub study 4: Dostarlimab and remzistotug 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+

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, 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-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, 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40377969/

Phase II Study Evaluating the Efficacy of Niraparib and ... We designed a single arm, open label, Phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.6046

Phase II study evaluating the efficacy of niraparib and ... A phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent/metastatic head and neck squamous cell carcinoma.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04313504

NCT04313504 | Study Evaluating the Efficacy of Niraparib ... Recurrent and/or metastatic HNSCC patients will be treated with combination of the PD-1 inhibitor (dostarlimab) and PARPi (niraparib) concurrently and ORR, PFS ...

4. aacrjournals.org aacrjournals.org/cancerrescommun/article/doi/10.1158/2767-9764.CRC-25-0192/762454/am/Phase-II-study-evaluating-the-efficacy-of

Phase II study evaluating the efficacy of niraparib and ... Phase II study evaluating the efficacy of niraparib and dostarlimab (TSR-042) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06256588

NCT06256588 | A Study of Dostarlimab vs Placebo After ... The goal of this study is to assess the safety and effectiveness of Dostarlimab compared to Placebo in adult participants with Head and Neck Squamous Cell ...

6. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/6/939/762896/Phase-II-Study-Evaluating-the-Efficacy-of

Phase II Study Evaluating the Efficacy of Niraparib and ... We designed a single-arm, open-label, phase II clinical trial to evaluate the combination of niraparib and dostarlimab in patients with R/M HNSCC.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842824001173

Dostarlimab: Review on success story and clinical trials A recently published clinical trial reported 100 % remission of advanced rectal cancer without significant side effects in the participants.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10026921/

Dostarlimab: From preclinical investigation to drug approval ... Several ongoing studies are assessing the efficacy of the combination of dostarlimab and niraparib in different solid tumors including head and ...