TOP 2301: Neoadjuvant Chemo for NSCLC

NCT06385262 | Suspended Phase 2 FDA Drug

• 1 other identifier: Pro00114645
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

Brief Summary

In this open-label, two-arm, randomized phase 2 clinical trial, patients with clinical stage 1B-3A non-small cell lung cancer (NSCLC) will receive neoadjuvant chemotherapy and cemiplimab every 3 weeks for 3 cycles with or without alirocumab every 4 weeks prior to surgery. Eligible patients will be randomized with equal allocation to two treatment groups. Permuted block randomization algorithm will be used for treatment assignment with stratification factors: stage (1B, 2A, 2B, 3A), and performance status (0 vs. 1). The study hypothesis is that the addition of alirocumab to neoadjuvant chemoimmunotherapy will make tumor cells more immunogenic to cytotoxic T cells, resulting in an increase in complete pathologic responses in surgically resected tumor.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Compare pathologic complete response (pCR) rate for neoadjuvant chemotherapy plus cemiplimab versus chemotherapy, cemiplimab, and alirocumab.

  Pathologic complete response (pCR) is defined as a lack of all signs of cancer in tissue samples removed during surgery or biopsy after neoadjuvant therapy.

  2 years

Secondary Outcomes (5)

• Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by objective response rate (ORR)

  2 years

• Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by disease-free survival (DFS)

  2 years

• Assess the preliminary efficacy of chemotherapy and cemiplimab with alirocumab as determined by overall survival (OS)

  2 years

• Determine the safety of neoadjuvant chemotherapy and cemiplimab with alirocumab in early-stage non-small cell lung cancer (NSCLC)

  2 years

• Determine the tolerability of neoadjuvant chemotherapy and cemiplimab with alirocumab in early-stage non-small cell lung cancer (NSCLC)

  2 years

Study Arms (2)

Arm A

EXPERIMENTAL

Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles with alirocumab (PCSK9 inhibitor) every 4 weeks prior to surgery

Drug: Alirocumab; Drug: Cemiplimab; Drug: Chemotherapy

Arm B

EXPERIMENTAL

Chemotherapy and cemiplimab (PD-1 inhibitor) every 3 weeks for 3 cycles without alirocumab (PCSK9 inhibitor) prior to surgery

Drug: Cemiplimab; Drug: Chemotherapy

Interventions

Alirocumab DRUG

300 mg subcutaneously every 4 weeks prior to surgery

Arm A

Cemiplimab DRUG

350mg IV every 3 weeks prior to surgery

Arm A; Arm B

Chemotherapy DRUG

Treating provider's choice of FDA approved platinum doublet chemotherapy IV every 3 weeks prior to surgery

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histological/cytological diagnosis of non-small cell lung cancer (NSCLC). Patient is eligible to enroll in the study based on clinical suspicion of NSCLC but are required to have a histological diagnosis of NSCLC in order to be eligible to receive treatment on study.
• Clinical stage IB, IIA/IIB, or III (N0-2) amenable to surgical resection.
• Primary tumor size of ≥ 3 cm (for all clinical stages to insure adequate tumor for correlative studies).
• Agrees to research blood collections for study.
• Deemed a surgical candidate.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• No prior chemotherapy, radiation therapy or biologic/targeted therapy for current diagnosis of lung cancer.
• Measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
• No active invasive malignancy in the past 2 years other than non-melanoma skin cancer. Cancers that are in-situ are not considered invasive.
• Signed written informed consent including Health Insurance Portability and Accountability Act (HIPAA) according to institutional guidelines.
• Sexually active males and females of reproductive potential must agree to use an appropriate contraceptive method during the study and for 120 days following the last dose of study drug.
• Females of childbearing potential must test negative for pregnancy within 48 hours prior to any initial study procedure based on a serum pregnancy test. (If subject uses appropriate contraceptive methods from the time of the initial serum pregnancy test, then the subsequent pregnancy test can be done within 72 hours prior to start of study treatment. If appropriate contraceptive measures are not begun immediately with the first serum pregnancy test, then subsequent serum pregnancy tests must be done within 48 hours prior to the start of study treatment.)
• Adequate organ function defined as:
• Absolute neutrophil count (ANC) ≥ 1500 per uL

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
• Participants with known EGFR mutations, ALK translocation, or ROS1 translocation. If testing is done, an FDA-approved assay should be used.
• Known history of active TB (Bacillus Tuberculosis).
• Hypersensitivity to alirocumab or any of its excipients.
• Concurrent administration of any other anti-tumor therapy.
• Prior therapy with an anti-PD-1, anti-PD-L-1, or anti-PD-L2 agent.
• Therapy with an anti-PCSK9 agent within 90 days of study entry.
• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Inability to comply with protocol or study procedures.
• Active infection requiring antibiotics, antifungal or antiviral agents, that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or HCV infection; or diagnosis of immunodeficiency. Exceptions:
• Patients with HIV who have controlled infection (undetectable viral load and CD4 count above 350 either spontaneously or on a stable antiviral regimen) are permitted.
• Patients with HBV (hepatitis B surface antigen positive) who have controlled infection (serum hepatitis B virus DNA polymerase chain reaction (PCR) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted.
• Patients who are HCV antibody positive (HCV Ab +) who have controlled infection (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted.

Sponsors & Collaborators

• Duke University: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alirocumab; cemiplimab; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Neal Ready, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 26, 2024
• Study Start: March 17, 2025
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): October 30, 2029
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)