BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab

NCT04933903 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BrUOG 397
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This single-arm phase 2 study will enroll patients with resectable and operable stage IB - III non-small cell lung cancer and treat them with pre-operative ipilimumab + nivolumab plus low-dose stereotactic body radiation therapy (SBRT) delivered concurrently. Only patients who proceed to surgery will be evaluable for the primary endpoint. The primary efficacy outcome measurement will be pathologic response (including Major Pathologic Response (MPR), and Complete Pathologic Response (CPR)). Secondary outcome measures include safety, and exploratory biomarkers of immune response in pre- and post-operative blood and tissue. A two-stage design will stop the study if fewer than 3 of the first 9 evaluable patients do not achieve MPR. An early stopping rule for safety will stop the study if more than 12 patients are enrolled to find the first 9 evaluable patients.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients with a Pathologic Response

  Assess Pathologic Response (major pathologic response and complete pathologic response) following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab.

  From beginning of study treatment to approximately day 49-63 on study.

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Beginning of study treatment through 90 days post study treatment completion.

Study Arms (1)

Protocol Therapy

EXPERIMENTAL

Ipilimumab: 1mg/kg IV day 1. Nivolumab: 3mg/kg IV days 1, 15, 29. SBRT delivered as 1-2 fractions to the gross primary tumor and nodal disease following day 1 infusion and completed by day 3 (7Gy x 1; 4Gy x 2).

Drug: Ipilimumab; Drug: Nivolumab; Radiation: SBRT

Interventions

Ipilimumab DRUG

1mg/kg IV on day 1 (1 dose total)

Protocol Therapy

Nivolumab DRUG

3mg/kg (to a maximum of 240mg) IV on days 1, 15, 29 (+/- 3 days) (3 doses total)

Protocol Therapy

SBRT RADIATION

1 fraction or 2 fractions delivered to the gross primary tumor and nodal disease, following the first treatment with ipilimumab + nivolumab on days 1-3.

Protocol Therapy

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed NSCLC
• Age \> 18
• ECOG Performance Status 0-1.
• Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be \> 0.8 L or be \> 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
• Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
• N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
• Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level.
• No prior history of thoracic radiation.
• Adequate Organ and marrow function as defined below
• leukocytes ≥2,000/mcL,
• absolute neutrophil count ≥1,000/mcL,
• platelets ≥100,000/mcL,
• Hemoglobin \>8.0 g/dL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

You may not qualify if:

• Pathologically confirmed NSCLC \*
• Age \> 18 \*
• ECOG Performance Status 0-1.
• Pulmonary function capacity capable of tolerating the proposed lung resection. FEV1 at least 2 L. If less than 2 L, the predicted postoperative forced expiratory volume in 1 second (FEV1) must be \> 0.8 L or be \> 35% of the predicted value. Postoperative predicted DLCO ≥ 35% is required.
• Resectable stage IB-IIIB (T2-3N0, T1-T3N1-2) NSCLC (per the 8th Edition American Joint Committee on Cancer (AJCC) classification) who are candidates for surgery with intent of R0 resection. Invasive T3 disease (eg, phrenic nerve, pericardium, chest wall other than Pancoast superior sulcus) may be included if the surgeon and study team deem it to be resectable.
• N2 nodes must be discrete (ie, not invading surrounding structures). If patients have N2 disease, as suspected by CT or PET, histologic proof of N2 status is recommended.
• Patients must be evaluated by a Thoracic Surgeon prior to registration. Operability is defined as having adequate pulmonary, cardiac, renal, nutritional, musculoskeletal, neurologic, and cognitive capacity to undergo major pulmonary resection with acceptable morbidity and mortality. Absence of major associated comorbidities that increase the surgery risk to an unacceptable level. \*
• No prior history of thoracic radiation.
• Adequate Organ and marrow function as defined below
• leukocytes ≥2,000/mcL,
• absolute neutrophil count ≥1,000/mcL,
• platelets ≥100,000/mcL,
• Hemoglobin \>8.0 g/dL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Sponsors & Collaborators

• Brown University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; Nivolumab

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)

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

Study Officials

• Christopher G Azzoli, MD

  Brown University

  PRINCIPAL INVESTIGATOR

• Thomas A DiPetrillo, MD

  Brown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

BrUOG

CONTACT

401-863-3000; BrUOG@Brown.edu

Study Design

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

Study Record Dates

• First Submitted: October 15, 2020
• First Posted: June 22, 2021
• Study Start: October 5, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)