Induction Chemo-Nivo in Unresectable Stage III NSCLC

NCT06003075 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 85869
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the response rate, safety, and effectiveness of a combination therapy in patients with lung cancer.

Conditions

Lung Cancer, Nonsmall Cell; Lung Cancer Stage III

Keywords

Nivolumab; unresectable

Outcome Measures

Primary Outcomes (1)

• Response Rate After Induction

  post induction radiographic response by cat scan

  9 weeks

Secondary Outcomes (7)

• Change in Toxicity

  through study completion, up to 18 months

• Percent of Participants Receiving Surgery

  date of surgery, approximately 10 weeks

• Pathologic Complete Response (pCR)

  post surgery, approximately 10 weeks

• Major Pathological Response (MPR)

  post surgery, approximately 10 weeks

• Progression Free Survival (PFS)

  2 years

Study Arms (2)

Combination Chemotherapy and Nivolumab and Surgery

EXPERIMENTAL

Patients with lung cancer receiving combination therapy with surgery

Combination Product: Nivolumab and Chemotherapy; Drug: Nivolumab; Procedure: Post Induction Surgery; Radiation: Post Induction XRT

Combination Chemotherapy and Nivolumab and Radiation

EXPERIMENTAL

Patients with lung cancer receiving combination therapy with radiation

Combination Product: Nivolumab and Chemotherapy; Drug: Nivolumab; Radiation: Post Induction XRT

Interventions

Nivolumab and Chemotherapy COMBINATION_PRODUCT

3 cycles of the proposed nivolumab + platinum doublet (either pemetrexed + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for non squamous; or gemcitabine + carbo/cis or paclitaxel + carbo or docetaxel + carbo/cis for squamous) will be administered then CT and biopsy, followed by surgery with option for post-op NIVO-XRT, then 12 cycles NIVO at 480 mg IV every 4 weeks for 12 weeks

Combination Chemotherapy and Nivolumab and Radiation; Combination Chemotherapy and Nivolumab and Surgery

Nivolumab DRUG

Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation

Also known as: NIVO

Combination Chemotherapy and Nivolumab and Radiation; Combination Chemotherapy and Nivolumab and Surgery

Post Induction Surgery PROCEDURE

Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by surgery in patients whose tumors were unresectable stage IIIA-C at baseline on the basis of lymphadenopathy and are determined to be resectable after responding to induction chemotherapy-nivolumab. The participants have an option for post op XRT, then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles

Combination Chemotherapy and Nivolumab and Surgery

Post Induction XRT RADIATION

Induction Chemo-NIVO x 3 cycles then CT and biopsy, followed by concurrent Chemo and Nivo XRT (60Gy). Participants will receive concurrent thoracic radiation therapy using a standardized 3DCRT or IMRT technique on a linear accelerator operating at 2:6 MV beam energy. The target total dose of thoracic radiation therapy will be 60 Gy in 30 daily fractions of 2 Gy prescribed to the PTV. The participants then will receive NIVO at 480 mg IV every 4 weeks for 12 cycles.

Combination Chemotherapy and Nivolumab and Radiation; Combination Chemotherapy and Nivolumab and Surgery

Eligibility Criteria

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

You may qualify if:

• Squamous and non-squamous non-small cell lung cancer that is at baseline, unresectable stage IIIA-IIIC (8th edition AJCC) and not previously treated
• PD-L1 level needs to be measured with values 0-100% eligible
• EGFR/ALK/ROS1 Wild Type or unknown genetic alterations in these genes
• ECOG Performance Status ≤ 1
• Adequate organ and marrow function
• Adequate pulmonary reserve (e.g., FVC, FEV1, TLC, FRC, and DLCO) capable of tolerating the proposed lung resection
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Clinical risk assessment of cardiac function using the New York Heart Association Functional Classification class 2B or better
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment
• Any prior radiotherapy to the lung
• Any prior treatment for NSCLC
• Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Any history of a severe hypersensitivity reaction to any monoclonal antibody
• Any history of allergy to the study drug components
• primary tumors involving the esophagus
• pancoast tumors
• Patients cannot have primary tumors which would remain unresectable
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Nivolumab or other agents used in study
• Any active or history of autoimmune disease (including any history of inflammatory bowel disease), or history of syndrome that required systemic steroids or immunosuppressive medications
• Ongoing requirement for systemic corticosteroids greater than the equivalent of prednisone 10mg
• previous malignancies
• history of interstitial lung disease
• Patients requiring continuous supplemental oxygen

Sponsors & Collaborators

• Ralph G Zinner: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40506, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Nivolumab; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Therapeutics

Results Point of Contact

• Title: Dr. Ralph Zinner
• Organization: University of Kentucky

ralph.zinner@uky.edu

859-562-2864

Study Officials

• Ralph Zinner, MD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Chemo, biopsy, surgery with option for post op chemo or no surgery with concurrent chemo

Study Record Dates

• First Submitted: August 15, 2023
• First Posted: August 21, 2023
• Study Start: December 13, 2023
• Primary Completion: July 5, 2024
• Study Completion: July 5, 2024
• Last Updated: April 30, 2025
• Results First Posted: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)