Danvatirsen + Pembrolizumab for Head and Neck Cancer

(PEMDA-HN Trial)

Recruiting in Palo Alto (17 mi)

+31 other locations

Overseen by Ezra Cohen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Flamingo Therapeutics NV

Must not be taking: Steroids, Antivirals, Antimicrobials, others

Disqualifiers: Autoimmune, Cardiovascular, Pneumonitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing danvatirsen with pembrolizumab in patients with head and neck cancer that has returned or spread. Danvatirsen aims to stop cancer growth, and pembrolizumab helps the immune system attack the cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or have received a live vaccine recently, you may not be eligible to participate.

What data supports the effectiveness of the drug Danvatirsen + Pembrolizumab for head and neck cancer?

Research shows that pembrolizumab, a part of the treatment, is effective for recurrent or metastatic head and neck cancer, as it helps the immune system fight cancer cells. It is approved for use after other treatments have failed, indicating its potential benefit in challenging cases.

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What makes the drug Danvatirsen + Pembrolizumab unique for head and neck cancer?

The combination of Danvatirsen and Pembrolizumab is unique because it pairs an immune checkpoint inhibitor (Pembrolizumab) with another agent (Danvatirsen) to potentially enhance the immune response against head and neck cancer, offering a novel approach compared to traditional chemotherapy or single-agent immunotherapy.

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Eligibility Criteria

This trial is for adults with recurrent or metastatic head and neck squamous cell carcinoma that can't be cured by surgery. They must have a life expectancy of at least 3 months, measurable tumor growth, PD-L1 expression in the tumor, good organ function, and agree to birth control if necessary. Excluded are those with curable disease by local therapy, prior metastatic treatment, certain heart diseases, previous immunotherapy drugs like anti-PD-1/L1/L2 agents.

Inclusion Criteria

I am a man who is either surgically sterile or I agree to use birth control.

My tumor shows high PD-L1 levels according to an FDA-approved test.

Oxygen saturation on room air ≥92% by pulse oximetry

Exclusion Criteria

I have received treatment for advanced head and neck cancer before.

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

My condition can be treated with the goal of curing it.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive danvatirsen plus pembrolizumab or pembrolizumab alone in 21-day cycles

Up to 24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with radiologic tumor assessments every 6 weeks and survival follow-up every 12 weeks

Up to 18 months

Every 6 weeks (in-person) for tumor assessments, every 12 weeks (virtual) for survival follow-up

Participant Groups

The study compares two treatments: Danvatirsen combined with Pembrolizumab versus Pembrolizumab alone for first-line treatment of advanced head and neck cancer. Patients will be randomly assigned to either receive both drugs or just Pembrolizumab in an open-label Phase II trial.

Group I: Danvatirsen plus pembrolizumab Experimental Treatment 2 Interventions

Danvatirsen dosing: Week 1: Danvatirsen intravenously (IV) on Days 1, 3, and 5 Week 2 and subsequent weeks: Danvatirsen IV weekly Pembrolizumab dosing: Pembrolizumab every 3 weeks after the Danvatirsen dose.

Group II: Pembrolizumab Active Control 1 Intervention

Pembrolizumab IV every 3 weeks after the Danvatirsen dose.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Stony Brook Cancer Center Stony Brook, NY

University Hospitals Cleveland Cleveland, OH

University of Illinois Cancer Center Chicago, IL

Mary Bird Perkins Cancer Center Baton Rouge, LA

More Trial Locations

Who Is Running the Clinical Trial?

Flamingo Therapeutics NV Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019] Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Combination of pembrolizumab and lenvatinib is a potential treatment option for heavily pretreated recurrent and metastatic head and neck cancer. [2021] Immunotherapy has become the current standard of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). One potential approach to improve immunotherapy efficacy is to combine pembrolizumab, an anti-PD-1 agent, with lenvatinib, a potent multikinase inhibitor. In this study, we presented our up-to-date experience with pembrolizumab/lenvatinib combination therapy in heavily pretreated R/M HNSCC.

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

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022] Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.

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

Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens. [2023] Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear.

5. Greece pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023] Pembrolizumab exhibits anticancer efficacy in platinum-sensitive or platinum-unfit patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, no large-scale retrospective real-world data are available. This retrospective study aimed to examine the efficacy and safety of pembrolizumab in multiple facilities.

6. England pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. [2019] Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected.