Zanzalintinib + Pembrolizumab for Head and Neck Cancer

(STELLAR-305 Trial)

Recruiting in Palo Alto (17 mi)

+168 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Exelixis

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

Disqualifiers: Nasopharynx, Salivary gland, Brain metastases, others

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, double-blind, controlled Phase 2/3 trial of zanzalintinib in combination with pembrolizumab versus zanzalintinib-matched placebo in combination with pembrolizumab in subjects with PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) incurable by local therapies who have not received prior systemic therapy for recurrent or metastatic disease.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you should not have had prior systemic therapy for recurrent or metastatic disease.

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

Research shows that Pembrolizumab is effective in treating head and neck cancer, especially in patients whose tumors have high levels of PD-L1, a protein that can help the immune system recognize and attack cancer cells. ^{1 2 3 4 5}

What safety data exists for Zanzalintinib + Pembrolizumab in humans?

Pembrolizumab, also known as KEYTRUDA, has been evaluated for safety in patients with head and neck cancer. Common serious side effects include pneumonia (lung infection), breathing difficulties, confusion, vomiting, fluid around the lungs, and respiratory failure. Other significant side effects can involve the immune system attacking healthy organs, leading to issues like lung inflammation, liver problems, and thyroid disorders. ^{1 3 6 7 8}

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

The combination of Zanzalintinib and Pembrolizumab is unique because it pairs a novel drug with an established immune checkpoint inhibitor, Pembrolizumab, which blocks the PD-1 pathway to help the immune system attack cancer cells. This combination may offer a new approach for treating head and neck cancer, especially in cases where traditional treatments have limited effectiveness. ^{1 3 4 7 9}

Eligibility Criteria

Adults with PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma, which is incurable by local therapy. They must not have had prior systemic therapy for this condition in the metastatic setting unless it was over 6 months ago as part of treatment for advanced disease. Eligible tumor locations include the oropharynx, oral cavity, hypopharynx, and larynx.

Inclusion Criteria

My throat cancer has been tested for HPV.

I can provide a sample of my tumor, either from previous or new biopsies.

I am fully active or can carry out light work.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zanzalintinib in combination with pembrolizumab or zanzalintinib-matched placebo in combination with pembrolizumab

Approximately 33 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 17 months

Treatment Details

Interventions

• Pembrolizumab (Other)
• Zanzalintinib (Other)

Trial Overview The trial compares Zanzalintinib combined with Pembrolizumab to a placebo paired with Pembrolizumab in patients who haven't tried systemic therapy yet. It's randomized and double-blind, meaning neither doctors nor participants know who gets the real drug versus placebo.

Participant Groups

Group I: Zanzalintinib + Pembrolizumab Experimental Treatment 2 Interventions

Subjects with R/M HNSCC will receive zanzalintinib + pembrolizumab

Group II: Zanzalintinib-Matched Placebo + Pembrolizumab Placebo Group 2 Interventions

Subjects with R/M HNSCC will receive zanzalintinib-matched placebo + pembrolizumab

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Exelixis Clinical Site #2 Fullerton, CA

Exelixis Clinical Site #19 Chicago, IL

Exelixis Clinical Site #4 Saint Louis, MO

Exelixis Clinical Site #3 Shirley, NY

More Trial Locations

Who Is Running the Clinical Trial?

Exelixis Lead Sponsor

Merck Sharp & Dohme LLC Industry Sponsor

References

1. 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] Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.

2. United States pubmed.ncbi.nlm.nih.gov

Pembro Ups Survival in PD-L1-positive HNSCC. [2019] In a phase III trial, first-line treatment with single-agent pembrolizumab led to deep and durable responses among patients with head and neck tumors that expressed high levels of PD-L1.

3. 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] Pembrolizumab is used in patients with metastatic head and neck squamous cell carcinoma contingent upon the programmed death ligand-1 (PD-L1) combined positive score (CPS).

4. United States pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Pembrolizumab and Vorinostat in Recurrent Metastatic Head and Neck Squamous Cell Carcinomas and Salivary Gland Cancer. [2020] This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck (HN), and salivary gland cancer (SGC).

5. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023] This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC).

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] On August 5, 2016, the U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA injection, Merck Sharp & Dohme Corp., Kenilworth, NJ) for treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. Approval was based on the objective response rate (ORR) and duration of response (DoR) in a cohort of patients in a nonrandomized multi-cohort trial (KEYNOTE-012) that included 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. Patients received either intravenous pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks. ORR was determined by independent review according to Response Evaluation Criteria in Solid Tumors 1.1. ORR was 16% (95% confidence interval 11, 22) with a complete response rate of 5%. DoR ranged from 2.4+ months to 27.7+ months. Twenty-three of 28 responding patients (82%) had response durations of ≥6 months. Safety was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab. Frequent (≥2%) serious adverse reactions were 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 of pembrolizumab was considered acceptable in this patient population. As a condition of accelerated approval, Merck is required to conduct a confirmatory trial; this trial, KEYNOTE-040, is ongoing.

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

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019] Until recently, palliative options for the treatment of platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have been cytotoxic chemotherapy and EGFR inhibitors. These agents offer limited efficacy with substantial toxicity. The development of novel immune checkpoint inhibitors has challenged the standard treatment. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that blocks the interaction between PD-1, an immune checkpoint receptor and its ligands PD-L1 and -2. In August 2016, the US FDA approved the use of pembrolizumab in R/M HNSCC following disease progression on or after platinum-containing chemotherapy. This review highlights the pharmacology, therapeutic efficacy and tolerability data relevant to the use of pembrolizumab for the treatment of R/M HNSCC. Readers will gain greater insight into the HNSCC tumor microenvironment, available biomarkers, and learn about important clinical considerations associated with the use of pembrolizumab and similar immune checkpoint inhibitors.

8. England 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. [2022] Patients with recurrent or metastatic squamous cell carcinoma of the head and neck have few treatment options. We aimed to assess the safety, tolerability, and antitumour activity of pembrolizumab, a humanised anti-programmed death receptor 1 (PD-1) antibody, in patients with PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck.

9. 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] Pembrolizumab is a humanized monoclonal antibody that blocks interaction between programmed death receptor-1 (PD-1) and its ligands (PD-L1, PD-L2). Although pembrolizumab is approved for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), its role in the management of locally advanced (LA) disease is not defined. We report a phase IB study evaluating the safety and efficacy of adding pembrolizumab to cisplatin-based chemoradiotherapy in patients with LA HNSCC.