A Phase II Trial for MOR Antagonism With Axelopran to Enhance Immunotherapy in Head and Neck Cancer
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorGlycyx Therapeutics
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Previous severe hypersensitivity reaction to treatment with a monoclonal antibody, hypersensitivity to excipients components of drug product, or has a known sensitivity to any component of the anti-PD-1 antibody (if applicable).
Has received chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for nonapproved indications(s) and in the context of a research investigation) ≤ 14 days prior to the first dose of axelopran or within 5 drug half- lives (whichever is shorter) prior to the first dose of study intervention.
Has received any systemic therapy for recurrent/metastatic HNSCC.
Patients with any ongoing toxicity related to a prior cancer therapy that is Grade >2 and considered by the Sponsor to be a safety risk for the study will be excluded.
Trial design
Design model
Single group
Treatments tested in this trial
axelopran
DrugAxelopran 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).
Pembolizumab
DrugPembrolizumab will be given every 6 weeks for 18 cycles
Treatment groups
18 Participants
are divided into 1 treatment groupGroup A: Axelopran in combination with Pembrolizumab in PDL-1 positive patients with HNSCCExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Safety and Tolerability
To assess the safety of daily axelopran in combination with standard of care pembrolizumab in the first line treatment of R/M HNSCC patients with PD-L1 CPS ≥1 receiving opioids for pain control over a 12-week period.
Time frame
12 weeksSecondary outcomes
1
Spontaneous bowel motility (SBM)
To evaluate SBM number and form associated with cancer progression outcome
Time frame
5 and 12 weeks2
Overall Response Rate (ORR)
ORR by investigator assessment based on RECIST v1.1, to assess efficacy by Objective Response Rate (ORR), per Response Evaluation Criteria in Solid Tumors (RECIST) with pembrolizumab plus axelopran
Time frame
Approximately 18 months3
Duration of Response (DOR)
To evaluate Duration of Response (DOR), time from start of treatment to disease progression or death in patients who achieve CR or PR per RECIST v1.1.
Time frame
Approximately 18 monthsLocations
Sponsors and contacts
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Glycyx Therapeutics
Lead sponsor
National Cancer Institute (NCI)
Collaborator
Emory University
Collaborator
University of Pittsburgh
Collaborator
Source ClinicalTrials.gov
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