Clinical trial NCT06769698: A Study to See if Giving Fianlimab and Cemiplimab Together is Better Than Cemiplimab Alone at Treating Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Official title: Phase II Randomized Study of Fianlimab Plus Cemiplimab Versus Cemiplimab Plus Placebo in First-Line Treatment of Participants With Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Is Positive for PD-L1 Expression
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
Keywords: Recurrent or Metastatic (R/M)
Positive for Programmed Death Ligand 1 (PD-L1) Expression
Human Papillomavirus (HPV)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2025-01-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is researching an experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab compared against cemiplimab combined with placebo (a placebo looks like a treatment but does not contain any real medicine), collectively called "study drugs" in this form.

The study is focused on participants with head and neck cancers who have not been previously treated for head and neck cancer that has come back or spread to other parts of the body, referred to as recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

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

* What side effects may happen from taking the study drugs
* How much of each study drug is in the blood at different times
* Whether the body makes antibodies against the study drug(s) individually (which could make the study drugs less effective or could lead to side effects)
* Compatible research to better understand the study drugs and HNSCC


Eligibility criteria: Key Inclusion Criteria:

1. Have histologically confirmed (by local pathology) R/M HNSCC that is considered incurable by local therapies
2. Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx (patients with cervical neck node SCC with occult primary as described in the protocol
3. PD-L1 expression Combined Positive Score (CPS) ≥1 documented with a previously PD-L1 obtained Immunohistochemistry (IHC) result prior to screening, as described in protocol
4. Oropharynx cancer participants only: HPV status, based on a previously documented result prior to screening, must have been established in a surgical biopsy specimen or a core biopsy specimen as described in the protocol
5. At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as described in the protocol
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate organ and bone marrow function as described in the protocol

Key Exclusion Criteria:

Medical Conditions

1. Participants who have Progressive Disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC as described in the protocol
2. Participants who have a primary tumor site of nasopharynx, paranasal sinus or salivary gland (any histology)
3. Head and neck SCC with unknown primary site as described in the protocol
4. Participants with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date as described in the protocol
5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management
6. History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment.

   Prior/Concomitant Therapy
7. Participants who have received prior systemic anticancer therapy in the R/M HNSCC setting as described in the protocol
8. Participants with a condition requiring corticosteroid therapy (\>10 mg prednisone/prednisolone/day or equivalent) within 14 days of the first dose of study drug as described in the protocol

Note: Other protocol defined Inclusion/ Exclusion Criteria apply

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
Secondary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Severity of AEs
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of immune-mediated Adverse Events (imAEs)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of treatment-related AEs
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of Adverse Events of Special Interest (AESIs)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of Serious Adverse Events (SAEs)
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of AEs leading to discontinuation
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of AEs leading to death
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of laboratory abnormalities
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Disease Control Rate (DCR) per investigator assessment
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Duration of Response (DOR) per investigator assessment or death, whichever occurs first
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Progression-Free Survival (PFS) per investigator assessment or death, whichever occurs first
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Concentrations of cemiplimab in serum
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Concentrations of fianlimab in serum
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Incidence of Anti-Drug Antibody (ADA) to fianlimab
timeFrame: Up to 90 days after last study treatment, approximately 58 months
measure: Titer of ADA to fianlimab
timeFrame: Up to 90 days after last study treatment, approximately 58 months
Other outcomes:
Locations:
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: