Non Small Cell Lung CancerPhase 2NCT04933903
BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab
A Phase 2 study testing Ipilimumab, Nivolumab and SBRT in people with Non Small Cell Lung Cancer, run by Brown University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- Ipilimumab, Nivolumab and SBRT
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2021to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
- Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
- Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
- Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
Who cannot join
- 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.
Show all 24Show fewer
- 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
- creatinine within normal institutional limits OR creatinine clearance ≥50 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
- Patients are capable of giving informed consent and/or have an acceptable surrogate capable of giving consent on the subject's behalf.
- Nonpregnant and non-nursing. The effect of ipilimumab and nivolumab on the fetus is unknown.
- Women of childbearing potential (WOCBP) must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses >1 year.
- Evidence of postmenopausal status or negative urinary or serum pregnancy test for female premenopausal patients. Women will be considered postmenopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women <50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the postmenopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥50 years of age would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
- Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Rhode Island Hospital
Providence, Rhode Island, 02903
L BrUOG, 401-863-3000, BrUOG@Brown.edu
Thomas A DiPetrillo, MD
About this study
Official title: BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab for Patients With Resectable Stage IB - III Non-Small Cell Lung Cancer
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
- Being tested
- Ipilimumab, Nivolumab, SBRT
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IpilimumabDrug
1mg/kg IV on day 1 (1 dose total)
NivolumabDrug
3mg/kg (to a maximum of 240mg) IV on days 1, 15, 29 (+/- 3 days) (3 doses total)
SBRTRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Ipilimumab; Drug: Nivolumab; Radiation: SBRT |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From beginning of study treatment to approximately day 49-63 on study.
Secondary outcomes (1)
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Assess safety and operative morbidity following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab and surgery.
Measured: Beginning of study treatment through 90 days post study treatment completion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study start5 Oct 2021
- Primary completionOct 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Christopher G Azzoli, MD, Principal investigator, Brown UniversityThomas A DiPetrillo, MD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04933903
- Sponsor's protocol ID
- BrUOG 397
- Status last verified
- Aug 2026
- First submitted
- 15 Oct 2020
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BrUOG 397: NEO Rad (LOW): Neoadjuvant Low Dose Stereotactic Body Radiotherapy, Ipilimumab and Nivolumab for Patients With Resectable Stage IB - III Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT04933903
- Acronym / sponsor ID
- BrUOG 397
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 5 Oct 2021 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 22 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Protocol Therapy | Experimental | Drug: Ipilimumab, Drug: Nivolumab, Radiation: SBRTIpilimumab: 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ipilimumab1mg/kg IV on day 1 (1 dose total) | Drug | Protocol Therapy |
| Nivolumab3mg/kg (to a maximum of 240mg) IV on days 1, 15, 29 (+/- 3 days) (3 doses total) | Drug | Protocol Therapy |
| SBRT1 fraction or 2 fractions delivered to the gross primary tumor and nodal disease, following the first treatment with ipilimumab + nivolumab on days 1-3. | Radiation | Protocol Therapy |
Primary outcome
Number of Patients with a Pathologic Response
Time frame: From beginning of study treatment to approximately day 49-63 on study.
Assess Pathologic Response (major pathologic response and complete pathologic response) following neoadjuvant low dose SBRT, Ipilimumab and Nivolumab.
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: Beginning of study treatment through 90 days post study treatment completion.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christopher G Azzoli, MD principal investigator
Brown University
Thomas A DiPetrillo, MD principal investigator
Brown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ipilimumab, Nivolumab and SBRT in people with Non Small Cell Lung Cancer, run by Brown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact BrUOG (401-863-3000, BrUOG@Brown.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients with a Pathologic Response (time frame: From beginning of study treatment to approximately day 49-63 on study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.