Induction Chemo-Nivo in Unresectable Stage III NSCLC

Phase II Study of Induction Platinum Doublet in Combination With Nivolumab Followed by Surgery or Concurrent Chemoradiation in Unresectable Stage IIIA-C Non-small Cell Lung Cancer (NSCLC)

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

Study Overview

• Status: Terminated
• Conditions: Lung Cancer, Nonsmall Cell; Lung Cancer Stage III
• Intervention / Treatment: Drug: Nivolumab; Procedure: Post Induction Surgery; Radiation: Post Induction XRT; Combination product: Nivolumab and Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University Of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Use of any live vaccines against infectious diseases (e.g., influenza, varicella. etc.) within 4 weeks (28 days) of initiation of study therapy
• Active systemic infection requiring therapy
• Patients with uncontrolled intercurrent illness
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination Chemotherapy and Nivolumab and Surgery; Patients with lung cancer receiving combination therapy with surgery	Drug: Nivolumab; Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation; Other Names: NIVO; Procedure: Post Induction Surgery; 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; Radiation: Post Induction XRT; 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 product: Nivolumab and Chemotherapy; 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
Experimental: Combination Chemotherapy and Nivolumab and Radiation; Patients with lung cancer receiving combination therapy with radiation	Drug: Nivolumab; Participants will receive NIVO at 480 mg IV every 4 weeks for 12 cycles after either surgery or treated with concurrent chemotherapy-nivolumab-radiation; Other Names: NIVO; Radiation: Post Induction XRT; 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 product: Nivolumab and Chemotherapy; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate After Induction	post induction radiographic response by cat scan	9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Toxicity	To assess safety, investigators will evaluate the rate of toxicity as defined by the Common Toxicity Criteria for Adverse Effects (CTCAE) scoring system.	through study completion, up to 18 months
Percent of Participants Receiving Surgery	Rate of converting non-surgical stage III(A-C) to surgically resectable disease	date of surgery, approximately 10 weeks
Pathologic Complete Response (pCR)	Number of participants with Pathologic Complete Response. Pathologic complete response (pCR) is defined by a surgical pathology specimen	post surgery, approximately 10 weeks
Major Pathological Response (MPR)	MPR rate, defined as number of participants with ≤ 10% residual tumor in lung and lymph nodes	post surgery, approximately 10 weeks
Progression Free Survival (PFS)	PFS is defined as the duration of time from start of treatment to time of disease progression or death, whichever occurs first.	2 years
Overall Survival (OS)	defined as the duration of time from start of treatment to time of death	2 years
Change in Patient-reported Quality of Life as Measured by FACT-TOI	patient-reported Quality of Life as measured by FACT-TOI (Functional Assessment of Cancer Therapy - Trial Outcome Index); defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS (lung cancer scale) scores obtained from 7-item questionnaires from the FACT-L (Version 4.0). Questions are on a 5-point scale from 0-4, where 0 = "not at all" and 4 = "very much." Scores range from 0 to 84; higher score indicates better physical aspects of quality of life (QoL).	through study completion, up to 18 months

Collaborators and Investigators

• Sponsor: Ralph G Zinner
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Ralph Zinner, MD, University Of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Actual): July 5, 2024
• Study Completion (Actual): July 5, 2024

Study Registration Dates

• First Submitted: August 15, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 21, 2023

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 10, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Nivolumab; unresectable
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Nivolumab
• Other Study ID Numbers: 85869

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No