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

NCT07662720 · Status: NOT_YET_RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 18

Last updated 2026-07-15

No results posted yet for this study

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.

Conditions

  • Head and Neck Squamous Cell Carcinoma (HNSCC) - Recurrent/Metastatic (R/M)

Interventions

DRUG

axelopran

Axelopran is a investigational, orally administered, once daily, peripherally acting mu-opioid receptor antagonist administered in combination with pembrolizumab in patients with PD-L1 positive recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

DRUG

Pembolizumab

Pembrolizumab will be given every 6 weeks for 18 cycles

Sponsors & Collaborators

  • National Cancer Institute (NCI)

    collaborator NIH

  • Emory University

    collaborator OTHER

  • University of Pittsburgh

    collaborator OTHER

  • Glycyx Therapeutics

    lead INDUSTRY

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-07-15
Primary Completion
2027-08-31
Completion
2028-08-31
FDA Drug
Yes

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07662720 on ClinicalTrials.gov