Not Yet RecruitingPhase 1/2

A Phase II Trial for MOR Antagonism With Axelopran to Enhance Immunotherapy in Head and Neck Cancer

18 participantsStarted 2026-06-30

Plain-language summary

This Phase 2, open-label, multicenter study will evaluate the safety and preliminary efficacy of axelopran in combination with pembrolizumab in patients with PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Axelopran is a peripherally acting mu-opioid receptor antagonist being developed to address opioid-induced immunodeficiency, a condition that may impair anti-tumor immune responses and reduce the effectiveness of immune checkpoint inhibitors. Many patients with advanced HNSCC require opioid analgesics for cancer-related pain management. Emerging evidence suggests that opioid signaling may suppress immune function and diminish the therapeutic activity of PD-1/PD-L1 inhibitors. By blocking peripheral mu-opioid receptor signaling without affecting central analgesia, axelopran may restore immune competence and enhance response to pembrolizumab. Approximately 18 patients with PD-L1 positive recurrent or metastatic HNSCC will be enrolled in a two-stage design consisting of an initial futility assessment cohort followed by expansion to the full study population. Participants will receive axelopran in combination with standard pembrolizumab therapy and will be followed for efficacy, safety, and survival outcomes. The estimated study duration is approximately 36 months, including enrollment, treatment, and follow-up. The primary objectives are to evaluate objective response rate and assess the safety and tolerability of the combination regimen. Secondary and exploratory objectives include progression-free survival, overall survival, duration of response, and assessment of biomarkers related to immune activation and opioid-induced immunosuppression. This study aims to determine whether targeting opioid-mediated immune suppression can improve clinical outcomes in patients receiving immune checkpoint inhibitor therapy for advanced head and neck cancer.

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

. Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the trial has been fully explained and must be willing to comply with all trial requirements and procedures
. Male or female ≥ 18 years of age
. Recurrent/Metastatic Squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx, hypopharynx) that is considered incurable by local therapies, who are planning to receive pembrolizumab as first line therapy or for platinum failure. Platinum Failure is defined as recurrence/progression between 3-6 months from definitive platinum based chemoradiation therapy.
. PD-L1 Combined positive score (CPS) \>1. PD-L1 can be done by local CLIA certified laboratory.
. Has not received anti-PD-1 or Anti-PD-L1 mAb therapy for recurrent/metastatic disease. A patient that received anti-PD-1 or Anti-PD-L1 mAb therapy as part of upfront curative intent therapy is eligible as long as it has been at least 1 year since the last dose of anti-PD-1 or anti-PD-L1 mAb therapy.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Safety and Tolerability

Timeframe: 12 weeks

Trial details

NCT IDNCT07662720

SponsorGlycyx Therapeutics

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2027-08-31

View on ClinicalTrials.gov More Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M) trials

Plain-language summary

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

. Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the trial has been fully explained and must be willing to comply with all trial requirements and procedures
. Male or female ≥ 18 years of age
. Recurrent/Metastatic Squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx, hypopharynx) that is considered incurable by local therapies, who are planning to receive pembrolizumab as first line therapy or for platinum failure. Platinum Failure is defined as recurrence/progression between 3-6 months from definitive platinum based chemoradiation therapy.
. PD-L1 Combined positive score (CPS) \>1. PD-L1 can be done by local CLIA certified laboratory.
. Has not received anti-PD-1 or Anti-PD-L1 mAb therapy for recurrent/metastatic disease. A patient that received anti-PD-1 or Anti-PD-L1 mAb therapy as part of upfront curative intent therapy is eligible as long as it has been at least 1 year since the last dose of anti-PD-1 or anti-PD-L1 mAb therapy.

A Phase II Trial for MOR Antagonism With Axelopran to Enhance Immunotherapy in Head and Neck Cancer

Plain-language summary

Who can participate

Inclusion criteria

Questions worth asking your doctor

Questions for the trial coordinator

What they're measuring

Trial details

A Phase II Trial for MOR Antagonism With Axelopran to Enhance Immunotherapy in Head and Neck Cancer

Plain-language summary

Who can participate

Inclusion criteria

Questions worth asking your doctor

Questions for the trial coordinator

What they're measuring

Trial details

Exclusion criteria