A Trial of LNS8801 With or Without Pembrolizumab in Patients With Refractory Melanoma

The goal of this clinical trial is to understand if a new drug called LNS8801 can safely treat patients with melanoma. The primary question to be answered is what is the average length of time during which melanoma does not grow or spread after starting treatment with LNS8801? Researchers will compare LNS8801 taken alone or LNS8801 taken together with another drug called pembrolizumab to other therapies as decided by the treating doctor. 135 patients will be randomly (like flipping a coin) placed in 3 treatment groups. In the first group (LNS8801 only) - Patients will take 125mg tablet of LNS8801 by mouth once per day every day for up to 2 years. In the second group (LNS8801 + pembrolizumab) - Patients will take 125mg tablet of LNS8801 by mouth once per day plus 200 mg of pembrolizumab by IV infusion once every 3 weeks for up to 2 years. In the third group, called Physician's Choice (PC), patients will receive chemotherapy (dacarbazine or temozolomide) or immunotherapy (pembrolizumab, nivolumab/relatlimab or nivolumab/ipilimumab) as determined by their treating physician. How often the patient visits the clinic visits will depend on the treatment group. Besides returning to the clinic for treatment, the patient will undergo periodic safety assessments and other required study procedures such as imaging assessments.

Sex

All

Minimum age

18 Years

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.