Danvatirsen + Pembrolizumab for Head and Neck Cancer

(PEMDA-HN Trial)

Recruiting at 37 trial locations

Overseen By Flamingo Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Flamingo Therapeutics NV

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

Disqualifiers: Autoimmune, Cardiovascular, Pneumonitis, 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: 10

Duration: Up to 24 months

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs for a specific type of head and neck cancer that has returned or spread and cannot be cured with local treatment. It compares the effects of danvatirsen (an experimental treatment) combined with pembrolizumab against pembrolizumab alone. Pembrolizumab is already used for this cancer type, while danvatirsen is being tested to enhance treatment effectiveness. Individuals with squamous cell carcinoma in areas like the throat or mouth and who have a measurable tumor might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

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.

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

Research has shown that pembrolizumab, a treatment used in this study, is already approved for certain cancers, such as head and neck cancer. This approval indicates a proven safety record, although some patients have experienced side effects like tiredness and nausea.

For danvatirsen, less information is available, but the trial phase suggests it has shown some safety in earlier studies. Previous research did not find any major safety issues, but it remains under close monitoring.

This trial tests how well danvatirsen works with pembrolizumab. While pembrolizumab is well-studied, using it with danvatirsen is new. Therefore, updates from this trial about their combined safety are important to watch. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Danvatirsen and Pembrolizumab for head and neck cancer because it offers a novel approach to treatment. While most therapies for this cancer type, like chemotherapy and radiation, focus on directly killing cancer cells, Danvatirsen works by targeting the STAT3 pathway, which plays a critical role in cancer cell survival and immune system evasion. By pairing Danvatirsen with Pembrolizumab, an immunotherapy that blocks the PD-1 pathway to boost the immune response against cancer cells, researchers hope to enhance the overall effectiveness of treatment. This combination aims to not only attack cancer cells more effectively but also improve the immune system’s ability to fight the disease.

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

Research shows that pembrolizumab effectively treats head and neck cancer that has recurred or spread. It aids the immune system in identifying and attacking cancer cells. Patients previously treated with pembrolizumab have experienced positive outcomes. In this trial, one group of participants will receive pembrolizumab alone, while another group will receive a new combination of pembrolizumab with danvatirsen. Danvatirsen might further enhance the immune response. Early signs suggest this combination could be more beneficial than pembrolizumab alone. Ongoing studies aim to confirm the effectiveness of this combination. ^{1 2 4 6 7}

Who Is on the Research Team?

Ezra Cohen, MD

Principal Investigator

Moores Cancer Center at UC San Diego Health

Are You a Good Fit for This Trial?

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.

Must have given written informed consent (signed and dated)

Exclusion Criteria

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

I have an autoimmune disease treated with medication.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Danvatirsen
• Pembrolizumab

Trial Overview 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.

How Is the Trial Designed?

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.

Who Is Running the Clinical Trial?

Flamingo Therapeutics NV

Lead Sponsor

Trials

2

Recruited

110+

Published Research Related to This Trial

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

In a study of 66 patients with recurrent and metastatic head and neck squamous cell carcinoma treated with pembrolizumab, the one-year overall survival rate was 69.4%, indicating the regimen's effectiveness as a first-line therapy.

The depth of response (DpR) was found to be a significant predictor of survival outcomes, with a greater tumor reduction (≥-45%) correlating with improved overall survival and progression-free survival rates.

NCBI (Pubmed)

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. Saijo, K., Imai, H., Ouchi, K., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

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. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

A 69-year-old patient with relapsed squamous cell carcinoma showed significant improvement after 14 cycles of pembrolizumab, indicating its efficacy as a second-line treatment for metastatic head and neck cancer.

The patient developed severe immune-related adverse effects, specifically grade 4 mucositis and esophagitis, highlighting the importance of monitoring for such complications in patients receiving PD-1 inhibitors like pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. Acero Brand, FZ., Suter, N., Adam, JP., et al.[2019]

In a study of 14 heavily pretreated patients with recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), the combination of pembrolizumab and lenvatinib showed an objective response rate of 28.6%, indicating potential efficacy even in patients who had previously failed anti-PD-1 therapy.

The disease control rate was 42.9%, with an overall survival of 6.2 months and progression-free survival of 4.6 months, suggesting that this combination therapy may provide meaningful benefits for patients who have limited treatment options.

NCBI (Pubmed)

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. Chen, TH., Chang, PM., Yang, MH.[2021]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6113

PEMDA-HN, an open-label, phase II, randomized ... The current study aims at evaluating the first-line combination of DANVA with pembrolizumab, an anti-PD-1 agent approved as first-line monotherapy for RM HNSCC.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05814666

NCT05814666 | Activity and Safety of Danvatirsen and ... Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with ...

3. uclahealth.org uclahealth.org/clinical-trials/activity-and-safety-danvatirsen-and-pembrolizumab-hnscc

Activity and Safety of Danvatirsen and Pembrolizumab in ... Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with ...

4. withpower.com withpower.com/trial/phase-2-squamous-cell-carcinoma-of-head-and-neck-5-2023-b16d1

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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36219809/

Updated Results of the Phase III KEYNOTE-048 Study - PubMed Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048.

6. uhhospitals.org uhhospitals.org/uh-research/find-clinical-trials-and-studies/clinical-trials-search/activity-and-safety-of-danvatirsen-and-pembrolizumab-in-hnscc-pemda-hn-19332

Activity and Safety of Danvatirsen and Pembrolizumab in ... Open-label, Phase II, randomized, controlled study evaluating the efficacy and safety of danvatirsen in combination with pembrolizumab compared with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38043938/

Safety outcomes of pembrolizumab with platinum agent ... This study helps to characterize the safety profile and activity of pembrolizumab in combination with a platinum agent and taxane derivative ...