An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

NCT05500092 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2021-13627CA209-6K6
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 4

Brief Summary

An open label, randomized study of neoadjuvant nivolumab and chemotherapy, with or without sub-ablative stereotactic body radiation therapy, for resectable stage IIA to IIIB non-small cell lung cancer

Conditions

Resectable Stage IIA to IIIB Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Complete Pathological Response Rate

  Complete pathological response (CPR) rate observed after neoadjuvant therapy and surgical resection. Complete pathological response will be defined as the absence of tumor cells in the resected specimen upon histopathological examination. CPR rate will be reported as a percentage along with a 95% Confidence Interval for each study arm.

  After 3 cycles. Each cycle is defined as 3 weeks

Secondary Outcomes (2)

• Major Pathological Response

  After 3 cycles. Each cycle is defined as 3 weeks

• Event Free Survival

  From the time of enrollment up to approximately 5 years

Study Arms (2)

Nivolumab + Platinum Doublet Chemotherapy

ACTIVE COMPARATOR

All participants will receive platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. Carboplatinum (AUC=5) can be used instead of Cisplatin (75 mg/m2) from cycle 2 for Cisplatin induced neuro/oto/nephrotoxicity as long as the subject remains eligible for doublet chemotherapy. Participants with nonsquamous tumors will receive pemetrexed (500 mg/m2). Participants with squamous tumors will receive either docetaxel (75 mg/m2 on day 1) or gemcitabine (1000 mg/m2 on days 1, 8). Cycles will be every 3 weeks and a maximum of a 2 week delay will be permitted for resolution of toxicities.

Drug: Nivolumab; Drug: Platinum Doublet

Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3)

EXPERIMENTAL

SBRT will be delivered near the conclusion of cycle 1 with platinum-based doublet chemotherapy (PDC) along with nivolumab for 3 cycles every 3 weeks. The intent is to deliver SBRT on three consecutive days when the concentration of radiosensitizing chemotherapy agents in the subject's system is at a minimum, to minimize toxicity risks. It is expected that some subjects may not receive SBRT on three consecutive days due to machine breakdown, inclement weather, or other logistic issues. Subjects must not receive SBRT within 72 hours after a cisplatin or carboplatin infusion

Drug: Nivolumab; Radiation: (8gy x 3); Drug: Platinum Doublet

Interventions

(8gy x 3) RADIATION

sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor

Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3)

Platinum Doublet DRUG

Standard of care doublet platinum therapy

Also known as: Carboplatinum, Cisplatin, Pemetrexed, Docetaxel, Gemcitabine

Nivolumab + Platinum Doublet Chemotherapy; Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3)

Nivolumab DRUG

Patients randomized to the Nivolumab + Platinum Doublet Chemotherapy only arm will receive three cycles of nivolumab at a dose of 360 mg every three weeks along with a platinum-based chemotherapy doublet (cisplatin or carboplatin plus pemetrexed for adenocarcinoma, cisplatin or carboplatin plus docetaxel, paclitaxel, or gemcitabine for squamous NSCLC) with sub-ablative stereotactic radiation therapy (8 Gy x 3) directed at the primary lung tumor

Nivolumab + Platinum Doublet Chemotherapy; Nivolumab + Platinum Doublet Chemotherapy + SBRT (8gy x 3)

Eligibility Criteria

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

You may qualify if:

• Patient has histologically or cytologically proven clinical stages IIA (tumors \> 4 cm), IIB, IIIA, and IIIB (T3 or T4, N2) NSCLC (AJCC version 8) and is considered eligible for surgical resection with curative intent. Patients with 2 primary non-small cell lung cancers are allowed.
• Measurable disease, as defined by RECIST v1.1.
• Parenchymal lung tumor deemed to be amenable to treatment with sub-ablative stereotactic body radiation therapy, as determined by a co-investigator from Radiation Oncology
• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) obtained from the subject prior to performing any protocol-related procedures.
• Age \> 18 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• Aspartate aminotransferase (SGOT)/Alanine Aminotransferase (SGPT), and alkaline phosphatase ≤ 2.5 x institutional upper limit of normal (ULN).
• Serum creatinine clearance\>50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance (CL):
• Males:
• Creatinine CL (mL/min)

You may not qualify if:

• Participation in another clinical study with an investigational product during the last 3 weeks.
• Active other primary malignancy excepting:
• Malignancy treated with curative intent and with no known active disease and of low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ, in-situ urinary bladder cancer, treated localized prostate cancer and ductal carcinoma-in situ.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab, with the exceptions of intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Patients with Grade ≥2 neuropathy.
• Previous receipt of immunotherapy.
• Active or prior documented autoimmune or inflammatory disorders that has required systemic treatment in the past year (including inflammatory bowel disease \[e.g., colitis or Crohn's disease systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). No active diverticulitis within the previous 3 months. The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• History of allogeneic organ transplant.

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Bristol-Myers Squibb: collaborator
• Penn State University: collaborator
• Washington University School of Medicine: collaborator

Study Sites (4)

Washington University in St. Louis

St Louis, Missouri, 63130, United States

Location

Montefiore Medical Center-Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

White Plains Hospital (WPH)

White Plains, New York, 10601, United States

Location

Penn State Health Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Interventions

Nivolumab; Carboplatin; Cisplatin; Pemetrexed; Docetaxel; Gemcitabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Brendon Stiles, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: August 12, 2022
• Study Start: January 25, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): May 1, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)