Dostarlimab for Head and Neck Cancer

(JADE Trial)

Recruiting at 280 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: GlaxoSmithKline

Must not be taking: Anticancer, Experimental, Immunotherapy, others

Disqualifiers: Other cancers, Immunotherapy reactions, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

864 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Dostarlimab, an immunotherapy drug, for individuals with Head and Neck Squamous Cell Carcinoma (HNSCC). Researchers aim to determine if Dostarlimab is safe and effective compared to a placebo for those who have completed a treatment plan involving cisplatin and radiotherapy. The trial seeks participants with newly diagnosed, locally advanced cancer in areas like the mouth or throat, without distant metastasis. Joining the trial could advance research and potentially improve future treatments for this cancer type. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on any other anticancer or experimental therapy while participating.

Is there any evidence suggesting that Dostarlimab is likely to be safe for humans?

Research has shown that Dostarlimab was well-tolerated in past studies. In one study, all patients with advanced rectal cancer went into remission without major side effects. This suggests that Dostarlimab might be safe for people. However, treatments can affect everyone differently. Always consult a doctor to understand the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for head and neck cancer?

Unlike the standard treatments for head and neck cancer, which often include chemotherapy, radiation, and surgery, Dostarlimab offers a novel approach by targeting the PD-1/PD-L1 pathway. This pathway is a critical checkpoint in the immune system, and by inhibiting it, Dostarlimab helps the body's immune cells recognize and attack cancer cells more effectively. Researchers are excited about Dostarlimab because it could provide a more targeted therapy with potentially fewer side effects than traditional treatments. Additionally, its ability to boost the immune response might lead to better long-term outcomes for patients.

What evidence suggests that Dostarlimab might be an effective treatment for Head and Neck Cancer?

Research has shown that Dostarlimab has potential in treating certain cancers. In a recent trial, all patients with advanced rectal cancer experienced complete remission, meaning their cancer disappeared. In this trial, participants will receive either Dostarlimab or a placebo to evaluate its effectiveness in head and neck squamous cell carcinoma (HNSCC). Although more research is needed, early studies offer hope for Dostarlimab's effectiveness in targeting and treating cancer cells in HNSCC. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with locally advanced head and neck squamous cell carcinoma that cannot be removed by surgery. Participants should have completed chemoradiation therapy. Specific eligibility criteria are not provided, but typically include good organ function and no other serious medical conditions.

Inclusion Criteria

I have a specific type of throat or mouth cancer, treated with cisplatin and radiotherapy, with no spread to distant parts.

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

My organs are functioning well.

Exclusion Criteria

Participants who are pregnant, breastfeeding, or expecting to conceive children within the projected duration of the study

Participants receiving any other anticancer or experimental therapy

I have a history of lung scarring or inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo chemoradiation therapy as part of the initial treatment

6-8 weeks

Treatment

Participants receive Dostarlimab or placebo following chemoradiation

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab

Trial Overview The study is testing the safety and effectiveness of Dostarlimab, an immunotherapy drug, compared to a placebo (a substance with no active drug). It aims to see if Dostarlimab can improve outcomes after standard treatment with chemoradiation.

How Is the Trial Designed?

Group I: Arm A: Dostarlimab Experimental Treatment 1 Intervention

Group II: Arm B: Placebo Placebo Group 1 Intervention

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

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

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

Published Research Related to This Trial

In a phase II trial involving 41 patients with operable head and neck squamous cell carcinoma (HNSCC), preoperative treatment with olaparib, either alone or in combination with cisplatin or durvalumab, was found to be safe and resulted in a significant reduction in tumor cell proliferation, as indicated by a decrease in Ki67 of at least 25% in 44.8% of treated patients.

The treatment also modulated the tumor microenvironment, leading to increased levels of PD-L1 and changes in macrophage polarization, suggesting that combining olaparib with other therapies may enhance its antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. Moutafi, M., Koliou, GA., Papaxoinis, G., 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, 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 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 (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]

Duligotuzumab, when combined with chemotherapy, showed promising activity in treating recurrent/metastatic squamous cell cancer of the head and neck, with 67% of patients achieving objective responses, including complete and partial responses.

The combination therapy was associated with a higher frequency and severity of certain adverse events, such as neutropenia and anemia, compared to historical data, indicating that while effective, the treatment may increase the risk of chemotherapy-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of duligotuzumab (MEHD7945A) plus cisplatin/5-fluorouracil or carboplatin/paclitaxel for first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck. Jimeno, A., Machiels, JP., Wirth, L., et al.[2019]

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]

In the phase II HAWK study involving 112 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who had high PD-L1 expression, durvalumab showed an objective response rate of 16.2%, with a notably higher rate of 29.4% in HPV-positive patients.

Durvalumab was found to have an acceptable safety profile, with 57.1% of patients experiencing treatment-related adverse events, but none were fatal, indicating it could be a viable treatment option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Zandberg, DP., Algazi, AP., Jimeno, A., et al.[2020]

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. 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 ...

3. 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.

4. 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.

5. 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.

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. 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 ...