NCT05352672 - Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma | Crick

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Age ≥12 years on the date of providing informed consent 2. Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease 1. Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of \>6 months. Accrual of these patients is limited to approximately 10% of the total population enrolled. 2. Patients with acral and mucosal melanomas are eligible. Accrual will be limited to 10% of the total population. 3. Measurable disease per RECIST v1.1 1. Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available 2. Cutaneous lesions should be evaluated as non-target lesions 4. Performance status: 1. For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 2. For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years) 5. Anticipated life expectancy of at least 3 months Key Exclusion Criteria: 1. Uveal melanoma 2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment. 3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV) or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection 4. Unknown BRAF V600 mutation status as described in the protocol 5. Systemic immune suppression: 1. Use of immunosuppressive doses of corticosteroids (\>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder. 2. Other clinically relevant forms of systemic immune suppression 6. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed. 7. History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication. 8. Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they: 1. Received radiotherapy or another appropriate standard therapy for the brain metastases, 2. Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment 3. Did not require immunosuppressive doses of corticosteroids therapy (\>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment 4. Are asymptomatic with a single untreated brain metastasis \<10 mm in size 9. Participants with a history of myocarditis. Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Outcomes

Primary Outcomes

Progression-free survival (PFS)

Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR)

Time frame: Approximately 27 months

Secondary Outcomes

Overall survival (OS)

Time frame: Up to 96 months

Objective response rate (ORR)

Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR) or based on investigator assessment according to RECIST 1.1

Time frame: Up to 27 months

Disease control rate (DCR)

Per RECIST 1.1 based on BICR or based on investigator assessment according to RECIST 1.1

Time frame: Up to 27 months

Duration of response (DoR)

Per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1

Time frame: Up to 27 months

PFS

Based on investigator assessment according to RECIST 1.1

Time frame: Up to 27 months

Incidence of Adverse Events (AEs)

Including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and/ or immune-mediated adverse events (imAEs)

Time frame: Up to 90 days post last dose, approximately 6 years

Occurrence of interruption and discontinuation of study drug(s) due to AEs

Including TEAEs, AESIs, and/ or imAEs

Time frame: Up to 90 days post last dose, approximately 6 years

TEAEs leading to death

Time frame: Up to 6 years

Incidence of laboratory abnormalities

Will be graded using the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (version 5.0)

Time frame: Up to 90 days post last dose, approximately 6 years

Concentrations of cemiplimab in serum

Time frame: Up to 90 days post last dose, approximately 6 years

Concentrations of fianlimab in serum

Time frame: Up to 90 days post last dose, approximately 6 years

Incidence of anti-drug antibodies (ADA) to fianlimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Titer of anti-drug antibodies (ADA) to fianlimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Incidence of ADA to cemiplimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Titer of ADA to cemiplimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Incidence of neutralizing antibodies (NAb) to fianlimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Incidence of NAb to cemiplimab over time

Time frame: Up to 30 days post last dose, approximately 6 years

Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)

EORTC-QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Time frame: Up to 90 days post last dose, approximately 6 years

PROs as measured by EQ-5D-5L

The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.

Time frame: Up to 90 days post last dose, approximately 6 years

PROs as measured by Functional Assessment of Cancer Therapy melanoma (FACTM) (melanoma subscale only)

The FACTM is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACTM is scored on a 5 point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much.". A Higher score represents higher Health Related Quality of Life (HRQoL).

Time frame: Up to 90 days post last dose, approximately 6 years

PROs as measured by Patient Global Impression of Severity (PGIS)

The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".

Time frame: Up to 21 days post last dose, approximately 6 years

PROs as measured by Patient Global Impression of Change (PGIC)

The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"

Time frame: Up to 21 days post last dose, approximately 6 years

Change in physical functioning per EORTC QLQ-C30

EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Time frame: Baseline to Week 25

Change in role functioning per EORTC QLQ-C30

Time frame: Baseline to Week 25

Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30

Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Time frame: Baseline to Week 25

Change in physical functioning per EORTC QLQ-C30

Time frame: Baseline to end of study, approximately 6 years

Change in role functioning per EORTC QLQ-C30

Time frame: Baseline to end of study, approximately 6 years

Change in GHS/QoL per EORTC QLQ-C30

Time frame: Baseline to end of study, approximately 6 years

Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

Overview

Conditions

Interventions

Eligibility

Locations (210)

Outcomes

Primary Outcomes

Secondary Outcomes