Novel Immunotherapy Combinations for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

+126 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: GlaxoSmithKline

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Previous malignancies, Active tumor bleeding, others

No Placebo Group

Prior Safety Data

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}

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.

Trial 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 (Other)
• Dostarlimab (PD-L1 Inhibitor)
• GSK6097608 (Other)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

GSK Investigational Site Toronto, Canada

GSK Investigational Site Chicago, IL

GSK Investigational Site Saint Louis, MO

GSK Investigational Site Omaha, NE

More Trial Locations

Who Is Running the Clinical Trial?

GlaxoSmithKline Lead Sponsor

iTeos Therapeutics Industry Sponsor

References

1. 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.

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] Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. The availability of multiple anti-PD-(L)1 antibodies provides treatment and dosing regimen choice for patients with cancer. Here, we describe the nonclinical characterization of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, which binds with high affinity to human PD-1 and effectively inhibits its interaction with its ligands, PD-L1 and PD-L2. Dostarlimab enhanced effector T-cell functions, including cytokine production, in vitro. Since dostarlimab does not bind mouse PD-1, its single-agent antitumor activity was evaluated using humanized mouse models. In this model system, dostarlimab demonstrated antitumor activity as assessed by tumor growth inhibition, which was associated with increased infiltration of immune cells. Single-dose and 4-week repeat-dose toxicology studies in cynomolgus monkeys indicated that dostarlimab was well tolerated. In a clinical setting, based on data from the GARNET trial, dostarlimab (Jemperli) was approved for the treatment of adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer that had progressed on or following prior treatment with a platinum-containing regimen. Taken together, these data demonstrate that dostarlimab is a potent anti-PD-1 receptor antagonist, with properties that support its continued clinical investigation in patients with cancer.

3. 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.

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. 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.