Dostarlimab for Head and Neck Cancer

(JADE Trial)

Recruiting at 229 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

Trial Summary

What is the purpose of this trial?

The goal of this study is to assess the safety and effectiveness of Dostarlimab compared to Placebo in adult participants with HNSCC (Head and Neck Squamous Cell Carcinoma)

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.

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

Dostarlimab has been approved for treating certain types of endometrial cancer, showing it can be effective in cancers with specific genetic features. While there's no direct evidence for head and neck cancer, similar drugs targeting the same pathway have shown promise in treating these cancers. ^{1 2 3 4 5}

Is dostarlimab safe for humans?

Dostarlimab has been approved for certain types of cancer, and studies have shown it to be generally well tolerated in humans, with safety data from trials involving endometrial cancer and other solid tumors. In animal studies, it was also well tolerated, suggesting it is generally safe for human use. ^{1 2 3 6 7}

What makes the drug dostarlimab unique for treating head and neck cancer?

Dostarlimab is unique because it is a PD-1 monoclonal antibody that enhances the immune system's ability to fight cancer by blocking the PD-1 pathway, which is a mechanism that some cancers use to evade immune detection. This drug has shown promising results in other cancers with similar genetic profiles, such as mismatch repair-deficient tumors, and is being explored for its potential in head and neck cancer. ^{2 3 6 7 8}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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-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]

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]

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]

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 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]

References

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

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. [2023]

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

Dostarlimab: First Approval. [2021]

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

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

4. United States 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. [2019]

5. England 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. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

7. 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]

8. United States 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. [2023]