INBRX-106 + Pembrolizumab for Head and Neck Cancer

(HexAgon-HN Trial)

No longer recruiting at 100 trial locations

Overseen By Study Director - Inhibrx

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Inhibrx Biosciences, Inc

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Nasopharynx, Salivary glands, Immunodeficiency, 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

Compensation: Varies

Number of Visits: 3

Duration: up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with head and neck cancer that cannot be cured with local therapies. Researchers aim to determine if the new drug, INBRX-106, is more effective when combined with pembrolizumab (an immunotherapy drug) than pembrolizumab alone. They seek participants whose cancer exhibits a certain protein (PD-L1) level and who have tumors in specific areas, such as the mouth or throat. For those whose cancer has returned or spread and cannot be cured with surgery or radiation, this trial may be suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are on systemic steroid therapy or any other form of immunosuppressive therapy, you must stop it at least 7 days before the first dose of the study treatment.

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

Research has shown that combining INBRX-106 and pembrolizumab was safe in previous studies. Earlier trials found that most side effects were mild to moderate, such as minor rashes or fatigue, and were related to the immune system.

Pembrolizumab, the other drug in the trial, has FDA approval for several types of cancer. It is generally considered safe, though some people may experience side effects like tiredness, itching, or nausea.

Overall, evidence suggests that both treatments are well-tolerated. However, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for head and neck cancer involve chemotherapy, radiation, or the use of immune checkpoint inhibitors like pembrolizumab. However, researchers are excited about INBRX-106 combined with pembrolizumab because INBRX-106 is a novel therapeutic antibody that targets the 4-1BB receptor on immune cells, enhancing the body's immune response against cancer cells. This new mechanism of action could potentially improve the effectiveness of pembrolizumab, an existing immune checkpoint inhibitor, offering a more powerful approach to fighting head and neck cancer. By combining these two treatments, there is hope for better outcomes and potentially fewer side effects compared to traditional therapies.

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

Research shows that pembrolizumab, a type of medicine, effectively treats head and neck cancers by helping the immune system attack cancer cells. In this trial, one group of participants will receive pembrolizumab monotherapy, while another group will receive a combination of INBRX-106 and pembrolizumab. INBRX-106 is a new treatment targeting a protein called OX40, which also boosts the immune system against tumors. Early studies combining INBRX-106 with pembrolizumab suggest they might work well together to enhance this immune response. The goal is to determine if using both treatments is more effective than pembrolizumab alone for patients with certain head and neck cancers. These treatments are being tested together to see if they provide better results than pembrolizumab by itself. ^{1 2 6 7 8}

Who Is on the Research Team?

Clinical Lead

Principal Investigator

Inhibrx Biosciences, Inc

Are You a Good Fit for This Trial?

This trial is for adults with a specific type of head and neck cancer (HNSCC) that can't be cured by surgery or radiation. They must have high levels of a protein called PD-L1, not been treated before, and their cancer should be measurable by scans. Participants need to be fairly healthy overall (good performance status), able to provide tissue samples, and if they can have children, they must use effective birth control.

Inclusion Criteria

Has your cancer spread from your head/neck to other body parts?

Has your cancer been treated "since" it spread to other body parts?

Was your last treatment at least 6 months ago?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive INBRX-106 combined with pembrolizumab or pembrolizumab with placebo, administered by IV infusion every 3 weeks

up to 2 years

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• INBRX-106
• Pembrolizumab

Trial Overview The study is testing INBRX-106 combined with Pembrolizumab against just Pembrolizumab in patients with advanced head and neck cancer expressing high PD-L1 levels. It's designed to see which treatment works better as the first line of attack without previous treatments.

How Is the Trial Designed?

Group I: INBRX-106 plus pembrolizumab Experimental Treatment 2 Interventions

Participants will receive INBRX-106 plus pembrolizumab, both given by intravenous (IV) infusion every 3 weeks (QW3)

Group II: pembrolizumab monotherapy (+ placebo in phase 3 part) Active Control 2 Interventions

Participants will receive pembrolizumab (plus placebo in Phase 3), given by intravenous (IV) infusion every 3 weeks (QW3)

Who Is Running the Clinical Trial?

Inhibrx Biosciences, Inc

Lead Sponsor

Trials

9

Recruited

1,700+

Inhibrx, Inc.

Lead Sponsor

Trials

9

Recruited

1,700+

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]

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]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[2022]

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 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 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 of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, 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 II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06295731

Study Details | NCT06295731 | INBRX-106 in Combination ... This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody INBRX-106 combined with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS6109

HexAgon-HN: Phase 2/3, randomized study of the ... A phase 2/3, randomized study evaluating INBRX-106 + pembro vs pembro alone as first-line treatment for R/M HNSCC with a PD-L1 CPS of ≥20.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04198766

NCT04198766 | Study of INBRX-106 and ... Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 ...

4. inhibrx.com inhibrx.com/inbrx-106-phase-2-3-trial/

Phase 2/3 Trial of INBRX-106 + Pembrolizumab in 1L R/M ... Phase 2/3, randomized study of INBRX-106 for Patients with Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC).

5. sciencedirect.com sciencedirect.com/science/article/pii/S1053429625000098

Metastatic Head and Neck Cancer: Immunotherapy and ... The anti-PD1 antibody pembrolizumab (Keytruda, Merck, Rahway, New Jersey) has demonstrated clinical success and has received FDA approval for the treatment of a ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-04886

INBRX-106 in Combination With Pembrolizumab in First- ... This seamless phase 2/3 randomized controlled study will evaluate the efficacy and safety of the hexavalent OX40 agonist antibody INBRX-106 combined with ...

7. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A747.full

651 Phase 2/3 study of the hexavalent OX40 agonist ... In an ongoing phase 1/2 study (NCT04198766), INBRX-106 + pembro has demonstrated a favorable safety profile, robust pharmacodynamics, and promising clinical ...

8. inhibrxbiosciences.investorroom.com inhibrxbiosciences.investorroom.com/2022-01-04-Inhibrx-Announces-Initial-Phase-1-Dose-Escalation-Results-for-INBRX-106,-a-Novel-Hexavalent-OX40-Agonist,-in-Combination-with-Keytruda-R-Pembrolizumab-Along-with-Updated-Single-Agent-Data

Inhibrx Announces Initial Phase 1 Dose Escalation Results for ... INBRX-106 in combination with Keytruda was observed to be well tolerated, with predominantly mild or moderate immune-related toxicities noted.