Setanaxib + Pembrolizumab for Head and Neck Cancer

Recruiting at 45 trial locations

Overseen By Richard Philipson, CMO

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genkyotex Suisse SA

Must not be taking: Immunosuppressants, Steroids, CYP3A4 inhibitors

Disqualifiers: Immunosuppression, Autoimmune disease, HIV, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests setanaxib and pembrolizumab in patients with head and neck cancer that has returned or spread. Setanaxib may stop cancer growth, and pembrolizumab helps the immune system fight cancer. Pembrolizumab is now used for various cancers including head and neck cancer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use medications that are potent CYP3A4 or UGT1A9 inhibitors or inducers within 21 days before starting the trial treatment. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug pembrolizumab for head and neck cancer?

Pembrolizumab has been shown to be effective for treating recurrent or metastatic head and neck squamous cell carcinoma, with an objective response rate of 16% and some patients experiencing long-lasting responses. It was approved by the FDA for this use after showing antitumor activity and manageable side effects in clinical trials. ^{1 2 3 4 5}

Is the combination of Setanaxib and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been used in treating head and neck cancer and is generally considered safe, though it can cause serious side effects like pneumonia, breathing difficulties, confusion, and immune system-related issues. The safety of Setanaxib in combination with Pembrolizumab specifically hasn't been detailed, but Pembrolizumab alone has a manageable safety profile. ^{1 2 3 5 6}

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

The combination of Setanaxib and Pembrolizumab is unique because it pairs a novel drug, Setanaxib, with Pembrolizumab, an immune checkpoint inhibitor that blocks PD-1, to potentially enhance the immune system's ability to fight head and neck cancer, offering a new approach compared to traditional chemotherapy and EGFR inhibitors. ^{1 2 5 7 8}

Eligibility Criteria

Adults with recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are candidates for first-line pembrolizumab treatment. They must have adequate organ function, known HPV status, measurable disease per RECIST v1.1, a life expectancy over 6 months, and an ECOG performance status of 0 or 1. Women must use effective contraception and have a negative pregnancy test; men should also agree to use contraception.

Inclusion Criteria

My cancer can be measured and biopsied according to specific guidelines.

I am considered for my first treatment with pembrolizumab for my recurring or spreading head/neck cancer.

My cancer has returned or spread and cannot be removed by surgery.

Exclusion Criteria

Presence of any laboratory abnormality or condition that, in the opinion of the investigator, could interfere with or compromise a patient's treatment, assessment, or compliance with the protocol and/or study procedures

Any other condition that, in the opinion of the investigator, constitutes a risk or contraindication for the participation of the patient in the study, or that could interfere with the study objectives, conduct, or evaluation

I have cancer that has spread to my brain or spinal cord.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Setanaxib 800 mg twice daily and Pembrolizumab 200 mg intravenously every 3 weeks, or placebo and Pembrolizumab 200 mg intravenously every 3 weeks

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

Treatment Details

Interventions

• Pembrolizumab
• Placebo
• Setanaxib

Trial Overview The trial is testing the effectiveness of Setanaxib combined with Pembrolizumab versus a placebo with Pembrolizumab in shrinking tumors according to RECIST v1.1 criteria in patients with SCCHN. Participants will be randomly assigned to either receive Setanaxib or a placebo alongside standard Pembrolizumab therapy.

Participant Groups

Group I: Setanaxib 1600 mg and Pembrolizumab 200 mg Experimental Treatment 2 Interventions

Participants will be administered setanaxib at a dose of 1600 mg/day for the up to 24-month double-blind treatment period. Participants will also be administered Pembrolizumab 200 mg intravenously every 3 weeks.

Group II: Placebo and Pembrolizumab 200 mg Active Control 2 Interventions

Participants will be administered placebo for the up to 24-month double-blind treatment period. Participants will also be administered Pembrolizumab 200 mg intravenously every 3 weeks.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Genkyotex Suisse SA

Lead Sponsor

Trials

2

Recruited

130+

Calliditas Therapeutics Suisse SA

Lead Sponsor

Trials

2

Recruited

130+

Findings from Research

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]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

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]

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 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 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]

References

1. 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]

2. 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]

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

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. [2021]

4. England 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. [2021]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Greece pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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

8. 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]