LNS8801 alone or with pembrolizumab for people whose melanoma has stopped responding.
A Multicenter, Open-Label, Randomized, Controlled Study to Assess the Antitumor Activity of LNS8801 With and Without Pembrolizumab in Patients With Treatment-Refractory, Unresectable Melanoma
This trial will test whether LNS8801, by itself or combined with pembrolizumab, can keep melanoma that progressed after anti‑PD‑1 therapy from growing.
Quick facts
| Phase | Phase2; Phase3 |
|---|---|
| Study type | Interventional |
| Enrollment | 135 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Linnaeus Therapeutics, Inc. Industry-sponsored |
| Drugs / interventions | pembrolizumab, nivolumab, relatlimab, ipilimumab, chemotherapy, immunotherapy |
| Locations | 9 sites (Newport Beach, California and 8 other locations) |
| Trial ID | NCT06624644 on ClinicalTrials.gov |
What this trial studies
This is an open-label, randomized 1:1:1 multicenter trial enrolling about 135 patients who pass a prescreen blood test for the GPER C/C genotype. Eligible patients with unresectable or metastatic cutaneous melanoma who progressed on prior anti‑PD‑1 therapy will be assigned to LNS8801 alone, LNS8801 plus pembrolizumab, or a physician's choice arm that may include chemotherapy or other immunotherapies. LNS8801 is given orally daily; pembrolizumab is given IV every 3 weeks (with an option to switch to 400 mg every 6 weeks after 6 months), and treatment may continue for up to about 2 years. The trial’s primary focus is on safety, tolerability, and the length of time cancer does not grow (progression‑free survival) comparing the experimental arms to physician's choice.
Who should consider this trial
Good fit: Ideal candidates are adults with unresectable or metastatic cutaneous melanoma who are homozygous for the GPER C/C genotype, have progressed on prior anti‑PD‑1 therapy, have measurable disease, and have an ECOG performance status of 0–1.
Not a fit: Patients with non‑cutaneous melanoma subtypes (uveal, mucosal, acral lentiginous, blue nevus), those without the GPER C/C genotype, or those who have not progressed on anti‑PD‑1 therapy are unlikely to be eligible or to benefit.
Why it matters
Potential benefit: If successful, the treatment could extend the time the melanoma stays under control and provide a new option for patients whose disease stopped responding to prior immune checkpoint inhibitors.
How similar studies have performed: Combining novel small molecules with PD‑1 inhibitors has shown promise in some melanoma trials, but LNS8801 is a novel agent and has not yet been proven effective in this setting.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Confirmed unresectable and/or metastatic cutaneous melanoma. * 2 copies of the fully functional form of GPER protein-coding sequence. * Eligible for and willing to receive 1 or more of the physician's choice (PC) therapies. * Able to swallow tablets. * Progressed on treatment with an anti-PD-1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other therapies. * Received an anti-CTLA-4 and/or BRAF containing regimen or is not eligible for or has declined anti-CTLA-4 and/or BRAF therapy prior to and for this study. * Measurable disease. * Eastern Cooperative Oncology Group Performance Status of 0 to 1. Exclusion Criteria: * Blue nevus subtype, mucosal, acral lentiginous, or uveal/ocular/choroidal Melanoma. * Previous anti-cancer or investigational drug/device treatment within 4 weeks of the first dose of study drug. * Radiotherapy within 2 weeks of starting study drug. * Allogeneic tissue/solid organ transplant. * Unstable autoimmune or immunodeficiency disease. * Other concurrent health issues that would make participation or completion of the study difficult. * Prior reaction to anti PD-1 therapy that would make treatment with pembrolizumab unadvisable. * Other protocol-defined inclusion/exclusion criteria may apply.
Where this trial is running
Newport Beach, California and 8 other locations
- USC Newport Beach — Newport Beach, California, United States (Recruiting)
- UCSF — San Francisco, California, United States (Recruiting)
- Stanford — Stanford, California, United States (Recruiting)
- University of Colorado Anschutz — Aurora, Colorado, United States (Recruiting)
- University of Colorado — Denver, Colorado, United States (Recruiting)
- Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
- Dana Farber — Boston, Massachusetts, United States (Recruiting)
- University of New Mexico — Albuquerque, New Mexico, United States (Recruiting)
- UPenn — Philadelphia, Pennsylvania, United States (Recruiting)
Study contacts
- Study coordinator: Sudha Velayutham
- Email: svelayutham@lumabridge.com
- Phone: 210-563-8441
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.