Pembrolizumab + ALE.C04 for Head and Neck Cancer

No longer recruiting at 23 trial locations

Overseen By Luigi Manenti, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Alentis Therapeutics AG

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: CNS metastases, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for head and neck cancer that has recurred or spread and cannot be treated with local therapies. Researchers aim to assess the safety and effectiveness of ALE.C04, an experimental treatment, both alone and in combination with pembrolizumab, a drug that aids the immune system in fighting cancer. Participants will receive varying doses of ALE.C04 to determine the optimal dose for future treatments. This trial may suit individuals with head and neck squamous cell carcinoma that cannot be cured with local treatments and who have measurable disease. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have severe immune-related adverse events from prior treatments or certain dermatological conditions, you may be excluded. It's best to discuss your specific medications with the trial team.

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

Research shows that ALE.C04, a new treatment for head and neck cancer, is under study to ensure its safety. It is tested both alone and with pembrolizumab, a well-known cancer drug safely used in many patients with other cancers. The studies on ALE.C04 are in the early stages, so researchers focus on finding the right dose and ensuring safety for people.

In these studies, patients receive different doses of ALE.C04, and researchers closely monitor any side effects. So far, they are testing how well people tolerate the treatment. Since the trials are just beginning, the complete safety picture is still developing. However, combining ALE.C04 with pembrolizumab suggests some confidence in its potential safety.

Overall, the goal is to ensure ALE.C04 is safe and could help people with head and neck cancer. The research is ongoing, and the results will help determine if this treatment can be used more widely in the future. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ALE.C04 combined with pembrolizumab for head and neck cancer because this combination could offer a new approach to treatment. Unlike standard therapies like surgery, radiation, or chemotherapy, this combo uses pembrolizumab, an immunotherapy that helps the immune system attack cancer cells. ALE.C04 is a novel agent whose unique mechanism or active ingredient may enhance pembrolizumab's effects, potentially improving outcomes for patients. This innovative combination targets cancer in a way that could be more effective than current options.

What evidence suggests that this trial's treatments could be effective for Head and Neck Cancer?

Research has shown that ALE.C04, a new type of antibody, might help treat head and neck cancer. It enhances the effectiveness of other treatments, like PD-1 therapies, and aids the body's immune cells in attacking cancer. In this trial, some participants will receive ALE.C04 alone, while others will receive it in combination with pembrolizumab. Studies have found that using ALE.C04 with pembrolizumab may better dismantle cancer defenses. Although ALE.C04 remains under study, the FDA has granted it fast track status, indicating its promise as a treatment. Early results are hopeful, particularly for patients with Claudin-1 positive cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with incurable recurrent or metastatic head and neck squamous cell carcinoma. Participants must be able to consent, have measurable disease per RECIST 1.1, an ECOG performance status of 0 or 1, and provide tissue samples for specific biomarker analysis.

Inclusion Criteria

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

My oropharyngeal cancer has been tested for HPV.

You are capable and willing to provide written consent.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Dose Escalation

Dose escalation part for ALE.C04 monotherapy and in combination with pembrolizumab to determine safe and well-tolerated dose levels

21 days

Phase I Recommended Dose for Expansion

Two ALE.C04 dose levels (higher or lower) considered for combination with pembrolizumab

Phase II Randomized Combination

1:1 randomized trial assessing ALE.C04 and pembrolizumab combination versus pembrolizumab monotherapy

Up to 4.5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALE.C04
• Pembrolizumab

Trial Overview

The study is testing ALE.C04 alone and combined with pembrolizumab in patients with head and neck cancer. It aims to determine the safety profile, how the body processes ALE.C04, the recommended dose for Phase II trials, and its effectiveness against tumors.

How Is the Trial Designed?

Group I: Phase 1 Recommended Dose for Expansion Experimental Treatment 2 Interventions

Two ALE.C04 dose levels (higher or lower) will be considered for the combination with pembrolizumab

Group II: Phase 1 Dose Escalation Experimental Treatment 2 Interventions

ALE.C04 single agent: Three planned doses of ALE.C04 and ALE.C04 in combination with pembrolizumab. Once a certain dose level of ALE.C04 is considered safe and well tolerated, the first cohort of patients receiving ALE.C04 at a lower dose level combined with pembrolizumab will be initiated

Group III: Phase 2 Randomized Combination part Active Control 2 Interventions

ALE.C04 at RP2D combined to pembrolizumab compared to pembrolizumab monotherapy

ALE.C04 is already approved in United States for the following indications:

Approved in United States as ALE.C04 for:

• Recurrent or metastatic Claudin-1 (CLDN1)–positive head and neck squamous cell carcinomas (HNSCC)

Who Is Running the Clinical Trial?

Alentis Therapeutics AG

Lead Sponsor

Trials

4

Recruited

310+

Published Research Related to This Trial

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 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]

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 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, 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 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]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. Pei, R., Shi, Y., Lv, S., et al.[2021]

In a study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

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]

Citations

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Alentis Therapeutics Doses First Patient in Phase 1/2 ...

The first patient has been dosed in a Phase 1/2 clinical trial of ALE.C04, a Claudin-1 (CLDN1) targeting investigational antibody for the treatment of CLDN1+ ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT06054477

Study of ALE.C04 in Patients With Head and Neck Cancer

The purpose of this study is to evaluate the safety profile of ALE.C04 monotherapy and in combination with pembrolizumab, to characterize pharmacokinetics ...

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clinicaltrials.eu

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Ale.c04 – Application in Therapy and Current Clinical ...

C04 to pembrolizumab treatment can improve outcomes for patients with head and neck cancer. Safety and Efficacy Measures. The study is designed to ...

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onclive.com/view/fda-grants-fast-track-status-to-ale-c04-for-recurrent-or-metastatic-cldn1-hnscc

FDA Grants Fast Track Status to ALE.C04 for Recurrent or ...

ALE. C04 restored the efficacy of PD-1 treatment and T-cell infiltration. Moreover, the agent was found to disrupt the interface between CLDN1 ...

5.

cancernetwork.com

cancernetwork.com/view/fda-grants-fast-track-designation-to-ale-c04-in-cldn1-hnscc

FDA Grants Fast Track Designation to ALE.C04 in CLDN1+ ...

Investigators will assess the safety and pharmacodynamics of ALE.C04 in patients with CLDN1-positive head and neck squamous cell carcinoma ...

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cancer.gov

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Study of ALE.C04 in Patients With Head and Neck Cancer

The purpose of this study is to evaluate the safety profile of ALE.C04 monotherapy and in combination with pembrolizumab, to characterize pharmacokinetics ...