A Multi-Cohort Exploratory Study of Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC

Plain English Summary

Neoadjuvant Cemiplimab for the Treatment of Resectable NSCLC, HCC, and HNSCC in Adult Patients is a Phase 2 clinical trial sponsored by Regeneron Pharmaceuticals studying Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma. This study tests if a new drug combination (cemiplimab and potentially fianlimab) given before surgery can shrink tumors in adults with lung, liver, or head and neck cancers. It is for adult patients diagnosed with non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), or head and neck squamous cell carcinoma (HNSCC) who are candidates for surgery. Participation involves receiving study drugs before surgery, with regular medical check-ups and tumor biopsies to monitor response and side effects. Alternative treatments may include standard chemotherapy, radiation, or surgery alone, depending on the cancer type and stage. The trial aims to enroll 65 participants.

Official Summary

This study is being done to better understand whether or not cemiplimab by itself and in combination with other treatments given prior to surgery will cause your tumor to respond in a beneficial way; whether the drug(s) are safe and what side effects they cause; and other details about how they function in the body. One of the treatments that will be combined cemiplimab is another experimental drug called fianlimab. In this form, cemiplimab and fianlimab will each individually be called "study drug" or "study drugs" when combined. Cemiplimab (also known as REGN2810) and fianlimab (also known as REGN3767) are both a type of drug called a monoclonal antibody. Antibodies are proteins naturally found in your blood that fight infections. A monoclonal antibody is a special kind of antibody that is manufactured as a medication to target specific proteins in the body that may be involved in your cancer. * Cemiplimab is a drug that blocks the programmed death receptor 1 (PD-1), a cell receptor on immune cells * Fianlimab is a drug that blocks the action of a protein called lymphocyte activation gene (LAG)-33 (LAG-3)

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with a confirmed diagnosis of NSCLC, HCC, or HNSCC who are scheduled for surgery. Patients must be able to provide tumor biopsies and blood samples, and have a good general health status (ECOG 0 or 1). Individuals who have had recent cancer treatment (within 6 months), rapidly growing tumors, or certain other medical conditions may not be eligible. This trial is studying Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if the study drugs shrink the tumor significantly before surgery, making the cancer easier to remove and potentially improving long-term survival. The specific primary outcome measures are: Major pathologic response (MPR) at time of surgery for the NSCLC cohorts (At time of surgery); Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts (At time of surgery); Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort (At time of surgery). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a need for more effective pre-surgery cancer treatments to improve surgical outcomes and potentially reduce recurrence for difficult-to-treat cancers. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer, Hepatocellular Carcinoma, Head and Neck Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial explores novel immunotherapy combinations in a growing oncology market, with potential for significant patient benefit if successful, though early-phase studies carry inherent risks. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific study drugs, potential side effects, and how participation might affect your surgery timeline. Be prepared for regular clinic visits for drug infusions, blood draws, and tumor biopsies. Understand that you will need to delay surgery until after the pre-surgery treatment is completed. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 65 participants

Interventions

• DRUG: cemiplimab — Administered intravenous (IV)
• DRUG: Platinum Doublet — Administered intravenous (IV)
• DRUG: fianlimab — Administered IV

Primary Outcomes

• Major pathologic response (MPR) at time of surgery for the NSCLC cohorts (At time of surgery)
• Significant tumor necrosis (STN) at time of surgery is the primary endpoint for the HCC cohorts (At time of surgery)
• Major treatment effect (MTE) at time of surgery is the primary endpoint for the HNSCC cohort (At time of surgery)

Secondary Outcomes

• Delay to surgery (Surgery >28 days following the end of the cycle of last dose of cemiplimab)
• Event-free survival (EFS) (Up to 60 months following surgery)
• Disease-free survival (DFS) (Up to 60 months following surgery)
• Overall response rate (ORR) (Up to 60 months following surgery)
• Overall survival (OS) (Up to 60 months following surgery)

Full Eligibility Criteria

Key Inclusion Criteria:

* Patient must have a known diagnosis of NSCLC, HCC, or HNSCC as defined in the protocol
* Patient must be willing and able to provide blood samples at the indicated time points
* Patient must be willing and able to have excisional or core needle biopsies of tumor prior to initiation of cemiplimab as defined in the protocol
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Patient is determined to be a surgical candidate for resection of their tumor
* Adequate organ and bone marrow function as defined in the protocol

Key Exclusion Criteria:

* Patients who have had any systemic anti-cancer therapy or radiotherapy within 6 months prior to entering the study for their current tumor or a different primary tumor
* Patients whose tumor burden, or pace of tumor growth, in the opinion of the Investigator will not permit delaying surgery
* Patients who have participated in a study of an investigational agent or an investigational device within 4 weeks of study therapy or 5 half-lives (whichever is longer)
* Patients who have had major surgery within 14 days prior to initiation of neoadjuvant Therapy
* Patients with metastatic disease for whom the intent of surgery would not be curative
* Uncontrolled, intercurrent illness as defined in the protocol and as determined by the Investigator
* Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Has active autoimmune disease that has required systemic treatment in the past 1 year
* Has a known, additional malignancy that is progressing and/or requires active treatment. Exceptions include patients with: basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy; in situ cervical or anal cancer; prostate cancer on stable dose of hormonal therapy without rising prostate-specific antigen (PSA); breast cancer who have been treated with curative intent, who may be on hormonal therapy.
* Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent
* 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. A history of radiation pneumonitis in the radiation field is permitted as long as pneumonitis resolved ≥6 months prior to study treatment.
* Uncontrolled infection with human immunodeficiency virus (HIV), HBV or hepatitis C infection (HCV); or diagnosis of immunodeficiency as defined in the protocol
* NSCLC cohorts only: Patients do not have a history of smoking. History of smoking is defined as smoking ≥100 cigarettes in a lifetime.
* NSCLC cohorts only: Patients with tumors tested positive for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) gene translocations, or c-ros oncogene 1 (ROS1) fusions.

Note: Other protocol defined Inclusion/Exclusion criteria apply

Trial Locations

• Icahn School of Medicine at Mount Sinai, New York, New York, United States

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Hepatocellular Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Lung Cancer
• Liver Cancer
• Oral Cavity Cancer
• Pharyngeal Cancer
• Esophageal Cancer
• Gastrointestinal Cancers
• Oncology

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