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

NCT06624644 | Recruiting Phase 2 FDA Drug

• 1 other identifier: LNS-103
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Melanoma (Skin Cancer); Melanoma Stage IIIB-IV; Cutaneous Melanoma; Unresectable Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

• Compare progression-free survival (PFS) of LNS8801 + pembrolizumab vs PC arms as assessed by RECIST v1.1.

  Compare PFS between each of the 3 arms

  up to 2 years.

Secondary Outcomes (9)

• Overall Survival (OS) of LNS8801 + pembrolizumab with PC treatment

  up to 5 years after the end of treatment

• Hospitalization days of LNS8801 + pembrolizumab vs LNS8801 monotherapy vs PC arms.

  Length of hospital stay (assessed up to 10 days)

• Duration of Response (DOR) of LNS8801 + pembrolizumab vs LNS8801 monotherapy vs PC arms.

  up to 2 years.

• Overall Response Rate (ORR) of LNS8801 + pembrolizumab vs LNS8801 monotherapy vs PC arms.

  up to 2 years

• Duration of Disease Control (DDC) of LNS8801 + pembrolizumab vs LNS8801 monotherapy vs PC arms.

  up to 2 years.

Other Outcomes (9)

• OS in patients treated beyond progression vs those who stopped treatment at progression.

  up to 5 years after the end of treatment

• Change in quality of life (QOL) survey responses during therapy (QLQ-C30 questionnaire) on therapeutic intervention in LNS8801 + pembrolizumab vs LNS8801 monotherapy vs PC arms.

  At the beginning of Cycle 1 (each cycle 6 weeks), 2, and 3 then every 12 weeks for 1 year

• Subgroup analyses comparing patients with primary vs secondary resistance to prior PD-1 therapy, LDH, and extent of disease.

  Collected at screening

Study Arms (3)

LNS8801 Monotherapy

EXPERIMENTAL

125 mg LNS8801 by mouth every day

Biological: LNS8801

LNS8801 + Pembrolizumab

EXPERIMENTAL

125 mg LNS8801 by mouth every day plus 200 mg Pembrolizumab by IV infusion once every 3 weeks.

Biological: LNS8801; Biological: Pembrolizumab

Physician's Choice

ACTIVE COMPARATOR

patients may receive chemotherapy or immunotherapy as determined by physician.

Drug: Chemotherapy (dacarbazine or temozolomide); Biological: Immunotherapy (Pembrolizumab); Biological: Immunotherapy (nivolumab and relatlimab); Biological: Immunotherapy (ipilimumab and nivolumab)

Interventions

LNS8801 BIOLOGICAL

G protein-coupled estrogen receptor (GPER) agonist

LNS8801 + Pembrolizumab; LNS8801 Monotherapy

Pembrolizumab BIOLOGICAL

Recombinant monoclonal antibody (anti-PD1)

LNS8801 + Pembrolizumab

Chemotherapy (dacarbazine or temozolomide) DRUG

chemotherapy (dacarbazine, temozolomide)

Physician's Choice

Immunotherapy (Pembrolizumab) BIOLOGICAL

pembrolizumab

Physician's Choice

Immunotherapy (nivolumab and relatlimab) BIOLOGICAL

nivolumab and relatlimab

Physician's Choice

Immunotherapy (ipilimumab and nivolumab) BIOLOGICAL

ipilimumab and nivolumab

Physician's Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed unresectable and/or metastatic cutaneous melanoma.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Linnaeus Therapeutics, Inc.: lead

Study Sites (9)

USC Newport Beach

Newport Beach, California, 92663, United States

RECRUITING

UCSF

San Francisco, California, 94143, United States

RECRUITING

Stanford

Stanford, California, 94305, United States

RECRUITING

University of Colorado Anschutz

Aurora, Colorado, 80045, United States

RECRUITING

University of Colorado

Denver, Colorado, 80204, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 87535, United States

RECRUITING

Dana Farber

Boston, Massachusetts, 02215, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87106, United States

RECRUITING

UPenn

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; Drug Therapy; Dacarbazine; Temozolomide; Immunotherapy; Nivolumab; relatlimab; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Immunomodulation; Biological Therapy; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Sudha Velayutham

CONTACT

210-563-8441; svelayutham@lumabridge.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will be randomized 1:1:1 between LNS8801 + pembrolizumab, LNS8801 monotherapy, and PC arms. In the LNS8801 + pembrolizumab arm, LNS8801 will be administered every day per week and pembrolizumab will be administered 200 mg Q3W for up to 35 cycles (approximately 2 years; Note: Physicians may modify the pembrolizumab regimen to 400 mg Q6W pembrolizumab after 6 months of treatment, if appropriate). In the monotherapy arm, LNS8801 will be administered every day per week. In the PC arm, patients may receive chemotherapy (dacarbazine, temozolomide) or immunotherapy (pembrolizumab, nivolumab/relatlimab, nivolumab/ipilimumab). Patients' randomization will be stratified by normal or elevated baseline LDH, number of disease sites (\<3 or ≧3), and physician's determination of primary vs secondary resistance to prior anti-PD-1 therapy per SITC guidance. Patients who are on LNS8801 + pembrolizumab combination therapy may drop one of the study medications for safety reasons.

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 3, 2024
• Study Start: August 6, 2025
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2031
• Last Updated: April 22, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)