Axelopran and Nivolumab in PD-1-Refractory Metastatic Melanoma
ConditionUnresectable Cutaneous Melanoma
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJohn Kirkwood
About this trial
This first-in-human study will evaluate the safety, clinical activity, and immunologic effects of combining axelopran with nivolumab in patients with PD-1-refractory unresectable or metastatic cutaneous melanoma. Exploratory analyses incorporating opioid exposure history and post-hoc OPRM1 genotyping will inform future precision immuno-oncology strategies.
Eligibility criteria
Qualifiers
Primary resistance: Disease progression as best response, or stable disease lasting <6 months, following at least 6 weeks (approximately two cycles) of anti-PD-1-based therapy, with progression confirmed by RECIST v1.1.
Secondary (acquired) resistance: Disease progression occurring after an initial objective response (complete or partial response) or durable stable disease (≥6 months) per RECIST v1.1 while receiving anti-PD-1-based therapy, or within 12 weeks of discontinuation of anti-PD-1 therapy following prior clinical benefit.
Note: Disease must have been histologically confirmed through prior pathology assessment conducted as per SOC.
Note: Prior anti-PD-1-based therapy may have been administered as monotherapy or in combination with other agents.
Disqualifiers
Participant is not a candidate to continue anti-PD-1 therapy due to unresolved toxicities resulting from previous treatment with anti-PD-1 therapy.
Has an active autoimmune disease requiring systemic treatment within the past 3 months, or a syndrome that requires ongoing systemic steroids or immunosuppressive agents. Subjects with vitiligo, Graves' disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule.
Participant is taking a daily dose of opioids that is >30 morphine milligram equivalents (MME) i. Daily opioid doses ≤30 MME are allowed
Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.
Trial design
Treatments tested in this trial
- Axelopran
- Nivolumab
Treatment groups
28 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov