Active, not recruitingNCT02259621NA_00092076Updated Sep 10, 2026Results posted

Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable NSCLC

A Phase 2 interventional study of Nivolumab and Carboplatin in Non-Small Cell Lung Cancer, sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Active, not recruiting at 5 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-10.

Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 39
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

Read the detailed description

The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab +/- ipilimumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 and other immunotherapies in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.

In addition, an amendment to this study allows evaluation of the combination of nivolumab and the anti-CTLA4 antibody, ipilimumab in the neoadjuvant setting for the treatment of resectable NSCLC. In a large, multicohort, phase 1 trial, the ORR to combination ipilimumab and nivolumab therapy in patients unselected by PD-L1 status ranged from 39-47%. Incidence of grade 3-4 toxicity ranged from 33-37% across the combination ipilimumab and nivolumab cohorts which compares favorably with the rates of toxicity due to platinum doublet chemotherapy in this disease setting.

The current amendment includes addition of a third arm (Arm C) combining nivolumab and platinum-doublet chemotherapy in the neoadjuvant setting.

Conditions studied

Non-Small Cell Lung Cancer

Browse trials for

Carcinoma, Non-Small-Cell Lung 6,488

In context

Carcinoma, Non-Small-Cell Lung

6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.

This study's enrollment of 39 is below the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Histologically proven non-small-cell lung cancer (core biopsy required).
- Squamous or non-squamous histology
- Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at SKCCC or MSKCC
- Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed.
Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at SKCCC or MSKCC. This may include clinical stage IB (≥4cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.

ECOG performance status 0-1

-Adequate organ function as follows:

Leukocytes ≥ 2,000/mm3
Absolute neutrophil count (ANC) ≥ 1000/mm3
Platelet count ≥ 100,000/mm3
Hemoglobin ≥ 9 g/dL
Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the Cockcroft-Gault formula below):

Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL

Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL

Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the upper limit of normal
Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include DLCO
- The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for up to 23 weeks after the last dose of nivolumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 31 weeks after the last dose of nivolumab. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration. Women must not be breastfeeding.
- Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs.

Exclusion criteria

Exclusion Criteria:

Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
Administration of chemotherapy or any other cancer therapy in the pre-operative period.
Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
Subjects with a history of symptomatic interstitial lung disease.
Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
Known positive history or positive test for Human Immunodeficiency Virus or Acquired ImmunoDeficiency Syndrome (AIDS).
History of allergy to study drug components.
Women who are pregnant or nursing.
Men with female partners (WOCBP) that are not willing to use contraception.
Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 39 participants (actual)

Study arms

Experimental
Arm B- Nivolumab
Nivolumab administration: Three doses of nivolumab will be administered to enrolled patients on Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.
Drug: Nivolumab
Experimental
Arm C- Nivolumab, Carboplatin, & Paclitaxel
Nivolumab 360 mg IV, Carboplatin AUC 5 or 6 IV, and Paclitaxel 175 or 200 mg/m2 IV every 21 days for 3 cycles prior to planned surgery on Day 0.
Drug: Nivolumab · Drug: Carboplatin · Drug: Paclitaxel
Experimental
Arm A- Nivolumab and Ipilimumab
One dose of Nivolumab 3mg/kg IV \& Ipilimumab 1mg/kg will be administered to enrolled patients on Day-42, then 2 doses of Nivolumab 3mg/kg will be administered to enrolled patients on Day-28 and Day-14
Drug: Nivolumab · Drug: Ipilimumab

Interventions

DrugNivolumab
Anti-PD-1 Therapy
Also known as: BMS-936558 or MDX1106
DrugCarboplatin
Anti-PD-1 Therapy
Also known as: Paraplatin
DrugPaclitaxel
Anti-PD-1 Therapy
Also known as: Taxol, Onxal
DrugIpilimumab
Anti-PD-1 Therapy

What researchers measure

Primary outcomes

Safety as Measured by Number of Participants With Grade 3 and 4 Lab Abnormalities, as Defined by CTCAE v4.03
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites.
Time frame: 8 weeks
Safety as Assessed by Number of Grade 3 and 4 Adverse Events
Number of Grade 3 and 4 adverse events as defined by CTCAE v4.03 that occur while a subject is participating in the study.
Time frame: 8 weeks

Secondary outcomes

Pathologic Response
Pathologic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and nicvolumab, carboplatin, and paclitaxel in resected tumor and lymph nodes. The rate of major pathologic response, defined as \<10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.
Time frame: 6 weeks
Radiographic Response
Radiographic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and carboplatin and paclitaxel as defined by RECIST 1.1.
Time frame: 5 weeks

Results

Posted Mar 20, 2024

Participant flow

Participant flow — Overall Study
Milestone	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel
Started	9	16	14
Completed	9	16	14
Not completed	0	0	0

Outcome measures

PrimarySafety as Measured by Number of Participants With Grade 3 and 4 Lab Abnormalities, as Defined by CTCAE v4.03

Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites.

Time frame:: 8 weeks
Reported as:: Count of participants · Participants

Safety as Measured by Number of Participants With Grade 3 and 4 Lab Abnormalities, as Defined by CTCAE v4.03
Participants	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel
Safety as Measured by Number of Participants With Grade 3 and 4 Lab Abnormalities, as Defined by CTCAE v4.03	1	1	1

PrimarySafety as Assessed by Number of Grade 3 and 4 Adverse Events

Number of Grade 3 and 4 adverse events as defined by CTCAE v4.03 that occur while a subject is participating in the study.

Time frame:: 8 weeks
Reported as:: Number · events

Safety as Assessed by Number of Grade 3 and 4 Adverse Events
events	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel
Safety as Assessed by Number of Grade 3 and 4 Adverse Events	1	1	1

SecondaryPathologic Response

Pathologic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and nicvolumab, carboplatin, and paclitaxel in resected tumor and lymph nodes. The rate of major pathologic response, defined as \<10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.

Time frame:: 6 weeks

Results for this outcome have not been posted.

SecondaryRadiographic Response

Radiographic response to neoadjuvant nivolumab, nivolumab plus ipilimumab, and carboplatin and paclitaxel as defined by RECIST 1.1.

Time frame:: 5 weeks

Results for this outcome have not been posted.

Adverse events

Collected over From the time of first dose of study medication up to 8 weeks.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm A- Nivolumab and Ipilimumab	1/9 (11.1%)	1/9 (11.1%)	9/9 (100%)
Arm B- Nivolumab	0/16 (0%)	4/16 (25%)	15/16 (93.8%)
Arm C- Nivolumab, Carboplatin, & Paclitaxel	0/14 (0%)	2/14 (14.3%)	14/14 (100%)

Most frequent serious events

Showing 10 of 12

Most frequent serious events
Event	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel
hypoxiaRespiratory, thoracic and mediastinal disorders	0/9	2/16	0/14
adult repiratory distress syndromeRespiratory, thoracic and mediastinal disorders	1/9	0/16	0/14
posterior reversible encephalopathy syndromeNervous system disorders	0/9	0/16	1/14
subcutaneous emphysemaSkin and subcutaneous tissue disorders	0/9	0/16	1/14
hypotensionVascular disorders	0/9	1/16	0/14
pneumothoraxRespiratory, thoracic and mediastinal disorders	0/9	1/16	0/14
infusion reactionGeneral disorders	0/9	1/16	0/14
lung infectionInfections and infestations	0/9	1/16	0/14
atrial fibrillationCardiac disorders	0/9	1/16	0/14
sepsisInfections and infestations	0/9	1/16	0/14

Most frequent other events

Showing 10 of 80

Most frequent other events
Event	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel
constipationGastrointestinal disorders	1/9	4/16	8/14
alopeciaSkin and subcutaneous tissue disorders	0/9	0/16	8/14
dyspneaRespiratory, thoracic and mediastinal disorders	5/9	5/16	6/14
fatigueGeneral disorders	5/9	6/16	6/14
anorexiaMetabolism and nutrition disorders	3/9	2/16	7/14
coughRespiratory, thoracic and mediastinal disorders	4/9	6/16	1/14
arthralgiaMusculoskeletal and connective tissue disorders	4/9	4/16	1/14
nauseaGastrointestinal disorders	2/9	1/16	6/14
non-cardiac chest painGeneral disorders	2/9	6/16	0/14
rash maculo-papularSkin and subcutaneous tissue disorders	2/9	1/16	5/14

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel	Total
<=18 years	0	0	0	0
Between 18 and 65 years	4	5	5	14
>=65 years	5	11	9	25

Age, Continuous
Age, Continuous(years)	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel	Total
Mean	68 (53 to 84)	69 (52 to 81)	68 (46 to 78)	69 (46 to 81)

Sex: Female, Male
Sex: Female, Male(Participants)	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel	Total
Female	2	7	8	17
Male	7	9	6	22

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel	Total
Race/Ethnicity — White/Non-Hispanic	7	14	10	31
Race/Ethnicity — Black or African American/Unknown	0	1	0	1
Race/Ethnicity — White/Declined to answer	1	1	0	2
Race/Ethnicity — Unknown/Non-Hispanic	0	0	2	2
Race/Ethnicity — American Indian or Alaskan Native/Non-Hispanic	1	0	1	2
Race/Ethnicity — Other/Non-Hispanic	0	0	1	1

Region of Enrollment
Region of Enrollment(Participants)	Arm A- Nivolumab and Ipilimumab	Arm B- Nivolumab	Arm C- Nivolumab, Carboplatin, & Paclitaxel	Total
Canada	0	2	11	13
United States	9	14	3	26

Study locations

5 sites

Johns Hopkins at Bayview Medical Center
Baltimore, Maryland 21224, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland 21287, United States
Memorial Sloan Kettering
New York, New York 10065, United States
Swedish Cancer Insitute
Edmonds, Washington 98026, United States
Johnathan Spicer
Montreal, Quebec H4 3J1, Canada

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Study documents

Protocol and statistical analysis plan · Dec 21, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 10, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02259621
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators: Bristol-Myers Squibb
Responsible party: Sponsor
First posted: Oct 8, 2014
Start date: Sep 2014
Primary completion: Oct 14, 2022
Completion: Oct 2027 (estimated)
Results posted: Mar 20, 2024
Last update: Sep 10, 2026

Study contacts

Patrick Forde, MD

principal investigator · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

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