Setanaxib + Pembrolizumab for Head and Neck Cancer

No longer recruiting at 51 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining setanaxib and pembrolizumab in shrinking tumors for individuals with a specific type of head and neck cancer that has recurred or spread. Researchers aim to determine if this combination is more effective than pembrolizumab (also known as KEYTRUDA) with a placebo (a substance with no active treatment). The trial suits those diagnosed with recurrent or metastatic squamous cell head and neck cancer who are candidates for pembrolizumab as a first-line treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that the combination of setanaxib and pembrolizumab has been tested for safety in patients with head and neck cancer. Previous studies found that this combination can improve survival rates in these patients. While these studies focus on the treatment's effectiveness, they also carefully monitor its safety.

Participants in these studies did not report any unexpected side effects from using setanaxib and pembrolizumab together. However, like many cancer treatments, some common side effects were noted, such as tiredness and nausea. These side effects are typical for cancer treatments and were manageable for most patients.

Since this trial is in a middle phase, setanaxib, when used with pembrolizumab, has shown a reasonable safety profile so far, indicating it has been well-tolerated by patients up to this point in the research process. However, as with any medical treatment, participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Setanaxib combined with Pembrolizumab for head and neck cancer because Setanaxib offers a novel mechanism of action. Unlike most existing treatments like chemotherapy or radiation that directly attack cancer cells, Setanaxib works by targeting the body's response to oxidative stress, which can help reduce inflammation and potentially slow cancer progression. Furthermore, when paired with Pembrolizumab, a well-known immunotherapy drug that helps the immune system recognize and attack cancer cells, this combination may enhance the overall effectiveness of treatment. This dual approach could offer a new and potentially more effective option for patients with head and neck cancer.

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

In this trial, participants will receive either the combination of setanaxib and pembrolizumab or a placebo with pembrolizumab. Studies have shown that using setanaxib with pembrolizumab can effectively treat advanced head and neck squamous cell carcinoma (SCCHN). Research indicates that this combination has extended patients' lives and delayed cancer progression. "Progression-free survival" refers to patients living longer without their cancer worsening. This treatment targets specific enzymes, NOX1/4, which aid tumor growth. These findings suggest that setanaxib with pembrolizumab could be a strong option for combating this type of cancer. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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]

Citations

1. healio.com healio.com/news/hematology-oncology/20240508/setanaxibpembrolizumab-combination-extends-survival-in-advanced-head-and-neck-cancer

Setanaxib-pembrolizumab combination extends survival in ... The combination of setanaxib and pembrolizumab improved survival outcomes in advanced head and neck cancer, according to topline data from a phase 2 study.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05323656

NCT05323656 | A Study of Setanaxib Co-Administered ... A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Setanaxib, When Administered With ...

3. onclive.com onclive.com/view/setanaxib-plus-pembrolizumab-elicits-pfs-benefit-in-recurrent-or-metastatic-hnscc

Setanaxib Plus Pembrolizumab Elicits PFS Benefit in ... The combination of the NOX1/4 inhibitor setanaxib and pembrolizumab produced progression-free survival benefits compared with placebo plus ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-setanaxib-and-pembrolizumab-for-patients-with-recurrent-or-metastatic-head-and-neck-squamous-cell-carcinoma/

Study on Setanaxib and Pembrolizumab for Patients with ... This clinical trial tests the efficacy and safety of Setanaxib in combination with Pembrolizumab in treating patients with recurrent or ...

5. cancerletter.com cancerletter.com/clinical-roundup/20240510_7e/

Setanaxib combination improves PFS and OS in SCCHN ... Pembro + standard-of-care improves survival in locally advanced head-and-neck cancer ... An international clinical trial co-led by WashU Medicine ...

6. onclive.com onclive.com/view/setanaxib-plus-pembrolizumab-improves-survival-in-recurrent-metastatic-hnscc

Setanaxib Plus Pembrolizumab Improves Survival in ... Setanaxib plus pembrolizumab improved progression-free survival and overall survival in recurrent or metastatic head and neck squamous cell carcinoma.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)02678-3/fulltext

703TiP A randomised, double-blind, placebo-controlled ... ... combination tx of setanaxib with pembrolizumab may improve clinical outcomes in CAF-rich tumours.3. Trial design. In this double-blind, placebo-controlled ...

8. cancernetwork.com cancernetwork.com/view/setanaxib-pembrolizumab-improves-survival-in-head-and-neck-cancer

Setanaxib/Pembrolizumab Improves Survival in Head and ... Phase 2 data also highlight an improvement in disease control rate with setanaxib/pembrolizumab in squamous cell carcinoma of the head and neck.