A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma

Melanoma Clinical Trial

Official title:

A Phase 2 and Phase 3 Peri-operative Trial of Fianlimab and Cemiplimab Compared With Anti-PD1 Alone in Patients With Resectable Stage III and IV Melanoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06190951
• Other study ID #: R3767-ONC-2208
• Secondary ID: 2022-502825-17-0
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: July 12, 2024
• Est. completion date: June 4, 2033

Study information

• Verified date: May 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with an approved medication called pembrolizumab. These types of study drugs are collectively known as immune checkpoint inhibitors. The study is focused on participants with a type of skin cancer known as melanoma.

The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to pembrolizumab as peri-operative therapy in participants with high-risk melanoma.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drug(s).

• How much study drug(s) is in the blood at different times.

• Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections.

• How administering the study drugs might improve quality of life.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 520
• Est. completion date: June 4, 2033
• Est. primary completion date: September 21, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c) per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and have histologically confirmed cutaneous melanoma that is deemed completely surgically resectable in order to be eligible as described in the protocol.

2. Patients with stage III melanoma must have clinically detectable disease that is confirmed as malignant on the pathology report. The pathology report must be reviewed, signed and dated by the investigator; this process will be confirmed during the interactive voice response system (IVRS) process as described in the protocol.

3. Patients must be candidates for full resection with curative intent and must be able to be surgically rendered free of disease with negative margins on resected specimens at surgery. The treatment plan including date of surgery must be documented by the investigator prior to randomization.

4. All patients must undergo full disease staging through a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging must include a computer tomography (CT) scan of the chest, abdomen, pelvis (if the primary tumor is on the head/neck then include a CT scan of head/neck), and all known sites of previously resected disease (if applicable) and brain magnetic resonance imaging (MRI) (or brain CT with contrast allowed if MRI is contraindicated).

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Key Exclusion Criteria:

Medical conditions:

1. Primary 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. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion or, if given to a target lesion, there is pathological evidence of disease progression in the same lesion.

4. 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 as described in the protocol.

Prior/concomitant therapy:

5. Use of immunosuppressive doses of corticosteroids (>=10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication as described in the protocol.

6. Treatment with any anti-cancer therapy for malignancies other than melanoma, including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol.

Other comorbidities:

7. Participants with a history of myocarditis.

8. History or current evidence of significant (CTCAE grade =2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.

Note: Other protocol-defined inclusion/ exclusion criteria apply

Related Conditions & MeSH terms

• Melanoma

Intervention

Drug:
• pembrolizumab
Administered intravenous (IV) every 3 weeks (Q3W) Phase 3 active comparator
• fianlimab
Administered IV Q3W Phase 2
• cemiplimab
Administered IV Q3W Phase 2 Active Comparator
• cemiplimab+fianlimab
Administered IV Q3W Phase 3 Either fianlimab HD or fianlimab LD in combination with cemiplimab will be chosen for Phase 3

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response (pCR) rate as assessed by local pathological review	Phase 2	Up to 1 year
Primary	Event-free survival (EFS)	Phase 3	Up to 4 years
Secondary	pCR rate as assessed by Blinded Independent Pathological Review (BIPR)	Phase 2 and Phase 3	Up to 1 year
Secondary	pCR rate as assessed by local pathological review	Phase 3	Up to 1 year
Secondary	EFS	Phase 2	Up to 4 years
Secondary	Distant metastasis-free survival (DMFS)	Phase 2 and Phase 3	Up to 4 years
Secondary	Overall survival (OS)	Phase 2 and Phase 3	Up to 4 years
Secondary	Major pathological response (MPR) as assessed by BIPR	Phase 2 and Phase 3	Up to 4 years
Secondary	MPR rate as assessed by local pathological review	Phase 2 and Phase 3	Up to 4 years
Secondary	ORR assessed by investigator per RECIST 1.1 criteria	Phase 2 and Phase 3	Up to 4 years
Secondary	ORR assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 criteria	Phase 2 and Phase 3	Up to 4 years
Secondary	Relapse-free survival (RFS)	Phase 2 and Phase 3	Up to 4 years
Secondary	Occurrence of treatment-emergent adverse events (TEAEs)	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of immune-mediated adverse events (imAEs)	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of serious adverse events (SAEs)	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of adverse events of special interest (AESIs)	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of TEAEs resulting in death	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of interruption or discontinuation of study drug(s) due to TEAE.	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of cancellation of surgery due to TEAE or delay to surgery	Phase 2 and Phase 3	90 days following last dose of study drug, approximately 4 years
Secondary	Occurrence of laboratory abnormalities	Phase 2 and Phase 3 grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	90 days following last dose of study drug, approximately 4 years
Secondary	Concentrations of fianlimab in serum	Phase 2 and Phase 3	Up to 4 years
Secondary	Concentrations of cemiplimab in serum	Phase 2 and Phase 3	Up to 4 years
Secondary	Anti-drug antibodies (ADA) in serum to fianlimab	Phase 2 and Phase 3	Up to 4 years
Secondary	ADA in serum to cemiplimab	Phase 2 and Phase 3	Up to 4 years
Secondary	Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale	Phase 2 and Phase 3 The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACT-M 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).	Up to 4 years
Secondary	Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30)	Phase 2 and Phase 3 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.	Up to 4 years
Secondary	Change from baseline in global health status/QoL per EORTC QLQ-C30	Phase 2 and Phase 3	Up to 4 years
Secondary	Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L)	Phase 2 and Phase 3 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.	Up to 4 years