Fianlimab&Cemiplimab as TotalNeoadj The (TNT) ForMelanoma

Fianlimab and Cemiplimab as Total Neoadjuvant Therapy (TNT) For Melanoma

This is a phase II, open label clinical trial determining efficacy of Fianlimab in combination with Cemiplimab in subjects with Melanoma. These are subjects who will have surgery to remove their cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Drug: Fianlimab; Drug: Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chao Family Comprehensive Cancer Center University of California, Irvine; Phone Number: 1-877-827-8839; Email: ucstudy@uci.edu
• Study Contact Backup: Name: University of California Irvine Medical

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center University of California, Irvine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years at the time of signing informed consent form (ICF) and able to independently complete informed consent. A certified translator must be used in the completion of informed consent for non-English speaking individuals.
• Patients must have surgically resectable, macroscopic Stage IIIB-D cutaneous melanoma or oligometastatic resectable stage IV (M1a, M1b, and M1c) melanoma per American Joint Committee on Cancer 8th Edition Staging Criteria. Patients are eligible at the time of the initial diagnosis or recurrence after previous surgery. Patients should have > 1 RECIST measurable lesion.
• Participants must have Eastern Cooperative Group (ECOG) performance status score of 0, 1 or 2 at initial screening.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, liver, and renal function:
• Hemoglobin >8.0 g/dL
• Platelets >75/mm3
• ANC >1.5/mm3
• Creatinine Clearance > 30mL/min
• AST and ALT less than 3 times the Upper Limit of Normal. participants with Gilbert's syndrome are excluded if total bilirubin > 3.0 × ULN; or direct bilirubin > 1.5 × ULN
• Total Bilirubin < 3.1.
• Albumin ≥ 3.0 g/dL
• Absolute neutrophil count ≥ 1.5 × 109/L
• Absolute lymphocyte count ≥ 0.5 × 109/L
• Women of childbearing potential must have had a negative pregnancy test performed within 7 days prior to the start of treatment.
• Females of childbearing potential and males must be willing and able to use a highly effective method of contraception to avoid pregnancy for the duration of the study and for at least 6 months after the last dose of study treatment. Acceptable means of contraception are listed in the fianlimab institutional brochure.
• Male participants must be willing to abstain from donating sperm from the time of enrollment until 6 months after administration of study interventions.

Exclusion Criteria:

• Participants with visceral, bone, or brain metastases.
• Participants with a local recurrence in scar or surgical bed of the primary melanoma as the sole site of disease.
• Participants with N1a or N2a only disease.
• Participants with a diagnosis of acral, ocular or mucosal melanoma.
• Participants with a history of a malignant disease that can interfere with interpretation of study results.
• Participants with previous treatment with investigational or standard immunotherapy for melanoma or other malignancy.
• Patients with a history of myocarditis.
• Patients with a TnT or troponin I (TnI) > 2x institutional ULN at baseline. Patients with Troponin T (TnT) or troponin levels between > 1 to 2x ULN are permitted if repeat levels within 24 hours are ≤ 1x ULN. If TnT or TnI levels are > 1 to 2x ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest.
• Participants with known untreated or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Known hypersensitivity to the active substances or to any of the excipients.
• Participants with a known history of chronic viral infections as indicated below.
• Known HBV infection defined as hepatitis B surface antigen reactive. NOTE: Participants with HBV infection on stable anti-viral therapy for > 4 weeks prior to the planned first study intervention and viral load confirmed as undetectable during Screening may be eligible.
• Known active HCV infection defined as detectable HCV RNA (qualitative) infection. NOTE: History of HCV is not exclusionary if participant has received curative treatment and viral load is confirmed as undetectable during Screening.
• HIV infection with CD4 count <200/microliter as measured within screening time period. Patients with HIV infectious should be on combination antiretroviral medication.
• History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.
• Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents except for the following: . The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
• Participants with a history of allogeneic tissue/solid organ transplant.
• Live vaccine within 30 days of the planned administration of a study drug.
• Positive pregnancy test during screening. Pregnant or lactating women are prohibited from enrolling in this study.
• Participants must not have any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study treatment administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 3 doses of neoadjuvant of Fianlimab in combination with Cemiplimab; 3 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 13 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks	Drug: Fianlimab; Given IV; Drug: Cemiplimab; Given IV
Experimental: 6 doses of neoadjuvant Fianlimab in combination with Cemiplimab; 6 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 10 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks	Drug: Fianlimab; Given IV; Drug: Cemiplimab; Given IV
Experimental: 8 doses of neoadjuvant Fianlimab in combination with Cemiplimab; 8 doses of neoadjuvant 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks, followed by Surgery and then 8 doses of 1600 mg Fianlimab in combination with 350 mg Cemiplimab every 3 weeks	Drug: Fianlimab; Given IV; Drug: Cemiplimab; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathologic Response (MPR) Rate by RECIST v1.1	Evaluate the major pathologic response (MPR), defined as pathologic complete response (pCR) + pathologic near complete response (pnCR) after treatment with dual checkpoint blockade in the index lymph node of Cohort 2 and Cohort 3	16 months
Major Pathologic Response (MPR) Rate by RECIST v1.1	Evaluate the MPR rate in the primary cutaneous melanoma site after wide local excision (if wide local excision was deferred after diagnostic biopsy)	16 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathologic Response (MPR) Rate by RECIST v1.1	Evaluate the major pathologic response (MPR), defined as pathologic complete response (pCR) + pathologic near complete response (pnCR) in Cohort 1.	16 months
Objective Response Rate (ORR) by RECIST v1.1	Sum of Complete Response (CR) and Partial Response (PR) by RECIST v 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1): Complete Response (CR) is defined as the disappearance of all target lesions; Partial Response (PR) is defined as a 30% decrease in the sum of diameters of target lesions. ORR = CR + PR for each dose cohort.	16 months
Event-Free Survival (EFS)	Determine the event-free survival (EFS) for each cohort. EFS is measured from the date of randomization to the first date of any of the following occurrences: disease progression that preclude surgery, toxicity from neoadjuvant treatment that precludes surgery, inability to surgically resect the primary lesion or undergo TLND, disease progression, toxic effects of adjuvant treatment if indicated, surgical complications, melanoma recurrence after surgery during the follow up period, or death from any cause.	28 months
Number of Patients with Adverse Events	Number of Patients who received at least one dose of Fianlimab with Cemiplimab with any reported Adverse Events (AEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.	28 months
Number of Patients with Immune Related Adverse Events	Number of Patients who received at least one dose of Fianlimab with Cemiplimab with reported immune related AEs (irAEs) using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.	28 months
Number of Patients who Discontinued Treatment Due to Reported Adverse Events	Number of Patients who received at least one dose of Fianlimab with Cemiplimab requiring discontinuation of therapy due to reported AEs using the CTCAE version 5.0 for reporting of nonhematologic AEs and modified criteria for hematologic AEs.	28 months

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: UC Cancer Consortium
• Investigators: Principal Investigator: Warren Chow, MD, Chao Family Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2030

Study Registration Dates

• First Submitted: April 7, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; cemiplimab
• Other Study ID Numbers: STUDY00000745; UCI 24-123 (Other Identifier: UCI CFCCC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No