Pembrolizumab + ALE.C04 for Head and Neck Cancer

Recruiting at 21 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

21 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety profile of ALE.C04 monotherapy and in combination with pembrolizumab, to characterize pharmacokinetics profile of ALE.C04, recommended Phase II dose (RP2D) for ALE.C04 in combination with pembrolizumab and to assess anti-tumor activity of ALE.C04 in combination with pembrolizumab in patients with Head and Neck Cancer.

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.

What data supports the idea that Pembrolizumab + ALE.C04 for Head and Neck Cancer is an effective treatment?

The available research shows that Pembrolizumab, when used alone or with chemotherapy, is effective for treating head and neck cancer, especially in cases where the cancer has returned or spread. Studies like KEYNOTE-048 and KEYNOTE-040 demonstrate that Pembrolizumab can help control the disease and has fewer side effects compared to traditional treatments like methotrexate, docetaxel, or cetuximab. This suggests that Pembrolizumab is a promising option for patients with this type of cancer. ^{1 2 3 4 5}

What safety data is available for Pembrolizumab in head and neck cancer treatment?

Safety data for Pembrolizumab (KEYTRUDA) in head and neck cancer treatment shows that it was evaluated in 192 patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Serious adverse reactions occurring in 2% or more of patients included pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders. The benefit-risk profile was considered acceptable for this patient population. ^{1 3 5 6 7}

Is the drug Pembrolizumab a promising treatment for head and neck cancer?

Yes, Pembrolizumab is a promising drug for head and neck cancer. It is approved for use in cases where the cancer has returned or spread after initial treatments. It works by helping the immune system fight the cancer more effectively. Pembrolizumab has shown potential in improving outcomes for patients with this type of cancer. ^{1 3 4 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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 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 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]

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]

References

1. United States 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. [2023]

2. United States 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

4. 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]

5. England 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. [2019]

6. England 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. [2019]

7. Greece pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Severe immune mucositis and esophagitis in metastatic squamous carcinoma of the larynx associated with pembrolizumab. [2019]

9. United States 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. [2021]