Eftilagimod Alpha + Pembrolizumab for Head and Neck Cancer

(TACTI-003 Trial)

Not currently recruiting at 30 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Immutep S.A.S.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Prior systemic therapy, Brain metastasis, 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: 2

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for head and neck cancer that has spread or returned and cannot be cured with standard treatments. Researchers are testing whether adding eftilagimod alpha (an experimental treatment) to pembrolizumab (Keytruda) proves more effective than using pembrolizumab alone. The trial includes patients whose tumors either show or do not show a specific protein called PD-L1. Individuals with head and neck cancer that cannot be treated with surgery or other local treatments, and who have not received certain previous treatments, might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on continuous systemic treatment with corticosteroids or other immunosuppressive medications, you may need to stop them at least 7 days before starting the trial.

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

Research has shown that combining eftilagimod alpha with pembrolizumab has yielded promising results in other studies. In patients with head and neck cancer, this combination proved safe and showed encouraging signs of combating the cancer. Specifically, a study involving patients with low levels of a protein called PD-L1 found the treatment well-tolerated, offering new hope for those with head and neck cancer.

Pembrolizumab alone has received FDA approval for various cancers, including some types of head and neck cancer, indicating its general safety. While every treatment can have side effects, these studies suggest that the combination of eftilagimod alpha and pembrolizumab has been safe for patients in the past. However, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine eftilagimod alpha with pembrolizumab (KEYTRUDA®), potentially enhancing the immune response against head and neck cancer. Unlike standard treatments that mainly rely on pembrolizumab alone, this combination uses eftilagimod alpha, a novel immune-boosting agent. Eftilagimod alpha works by activating and strengthening the patient’s immune system to better recognize and attack cancer cells. This unique combination targets the immune system differently, potentially offering a more effective option for patients, especially those whose immune systems need an extra push to combat the disease.

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

Research has shown that combining eftilagimod alpha with pembrolizumab may be promising for treating head and neck cancer, particularly in patients who are PD-L1–negative. In this trial, some participants will receive this combination. One study found that these patients lived a median of 17.6 months, a significant result. This combination appears to improve survival rates in cases with low PD-L1 scores, offering new hope for patients. Other participants will receive pembrolizumab alone, a well-known and effective cancer treatment. The combination aims to enhance these effects, potentially leading to better outcomes for more patients. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) that can't be cured by surgery or other local treatments. They must have a certain level of PD-L1 protein in their tumors, good physical health (ECOG 0-1), and no prior systemic cancer treatment for the recurrent/metastatic disease. People with brain metastases stable after treatment may join.

Inclusion Criteria

My cancer has been tested for PD-L1 using an FDA-approved method.

My head or neck cancer has returned or spread and cannot be cured with treatment.

I can carry out all my daily activities without help.

Exclusion Criteria

I have previously been treated with specific immune system targeting drugs.

I have stable brain metastases and haven't needed steroids for 14 days.

I have had at least one treatment for my cancer after it came back or spread, but not within the last 6 months if it was part of a combined treatment approach for advanced but not spread cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive eftilagimod alpha in combination with pembrolizumab or pembrolizumab alone for up to 24 months

24 months

Every 2-3 weeks for efti, every 6 weeks for pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eftilagimod alpha
• Pembrolizumab

Trial Overview The study tests Eftilagimod alpha combined with Pembrolizumab versus Pembrolizumab alone in treating HNSCC. It aims to see if adding Eftilagimod improves outcomes for patients whose tumors express different levels of the PD-L1 protein.

How Is the Trial Designed?

Group I: (CPS ≥1): pembrolizumab (KEYTRUDA®) + efti Experimental Treatment 2 Interventions

eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).

Group II: (CPS <1): pembrolizumab (KEYTRUDA®) + efti Experimental Treatment 2 Interventions

eftilagimod alpha: 30 mg every 2 weeks for the first 4 cycles;thereafter every 3 weeks for up to 18 cycles (1 cycle = 6 weeks). pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).

Group III: (CPS ≥1): pembrolizumab (KEYTRUDA®) Active Control 1 Intervention

pembrolizumab (KEYTRUDA®): 400 mg every 6 weeks for up to 18 cycles (1 cycle = 6 weeks).

Who Is Running the Clinical Trial?

Immutep S.A.S.

Lead Sponsor

Trials

15

Recruited

2,600+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase 3 study involving 495 patients with recurrent or metastatic head-and-neck squamous cell carcinoma, pembrolizumab demonstrated a median overall survival of 8.4 months, compared to 6.9 months for standard-of-care treatments, indicating a significant improvement in survival rates.

Pembrolizumab was associated with fewer severe treatment-related adverse events (13%) compared to standard-of-care therapies (36%), suggesting a better safety profile for patients receiving pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Cohen, EEW., Soulières, D., Le Tourneau, C., et al.[2019]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., 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]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a phase 1b trial involving 60 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, pembrolizumab was found to be well tolerated, with only 17% experiencing severe drug-related adverse events and no drug-related deaths.

The treatment showed clinically meaningful antitumor activity, with an overall response rate of 18%, and particularly higher in HPV-positive patients at 25%, indicating its potential as a viable therapy for advanced head and neck cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Seiwert, TY., Burtness, B., Mehra, R., et al.[2022]

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 involving 133 patients with locally advanced squamous cell carcinoma of the head and neck, pembrolizumab combined with radiotherapy did not show a significant improvement in locoregional control or survival compared to the standard treatment of cetuximab with radiotherapy.

However, patients receiving pembrolizumab experienced significantly lower toxicity, with only 74% reporting severe adverse events compared to 92% in the cetuximab group, suggesting it may be a safer option for patients unfit for high-dose cisplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Tao, Y., Biau, J., Sun, XS., et al.[2023]

Citations

1. onclive.com onclive.com/view/frontline-eftilagimod-alpha-pembrolizumab-yields-favorable-os-in-pd-l1-negative-hnscc

Frontline Eftilagimod Alpha/Pembrolizumab Yields ... Treatment with eftilagimod alpha plus pembrolizumab produced a median OS of 17.6 months in the first line for patients with PD-L1–negative HNSCC.

2. immutep.com immutep.com/detail/immutep-s-efti-in-combination-with-keytruda-r-pembrolizumab-drives-strong-overall-survival-in-head-and-neck-cancer-with-cps-1.html

Immutep's Efti in Combination with KEYTRUDA ... Immutep's Efti in Combination with KEYTRUDA® (pembrolizumab) Drives Strong Overall Survival in Head and Neck Cancer with CPS <1. May 5th 2025.

3. ascopubs.org ascopubs.org/doi/10.1200/OA-24-00102

Eftilagimod Alpha Plus Pembrolizumab in First-Line ... This phase II study investigated efti plus pembrolizumab treatment in patients with first-line metastatic non–small cell lung cancer (NSCLC) ...

4. oncodaily.com oncodaily.com/oncolibrary/immune-oncology/eftilagimod-alfa-for-head-and-neck-cancer

Positive FDA Feedback for Eftilagimod Alfa in Head and ... FDA supports ongoing development of eftilagimod alfa plus pembrolizumab in PD-L1–negative HNSCC after promising efficacy from Phase II data.

5. targetedonc.com targetedonc.com/view/eftilagimod-alfa-demonstrates-potential-in-pd-l1-low-head-and-neck-cancer

Eftilagimod Alfa Demonstrates Potential in PD-L1–Low ... Eftilagimod alfa shows promise as a novel immunotherapy for head and neck cancer patients with low PD-L1 expression, offering new treatment hope ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38995265/

Eftilagimod Alpha (Soluble LAG3 Protein) Combined with ... Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in patients with second-line head and neck squamous cell ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03625323

NCT03625323 | Combination Study With Soluble LAG-3 ... Evaluate the safety and efficacy of the combination of eftilagimod alpha with pembrolizumab in non-small cell lung carcinoma and head and neck carcinoma ...