A Study to Evaluate Two Dosing Regimens of Subcutaneous Nivolumab in Combination With Intravenous Ipilimumab and Chemotherapy in Participants With Previously Untreated Metastatic or Recurrent Non-Small Cell Lung Cancer (NSCLC) (CheckMate-1533)

A Phase 2, Open-label, Randomized Trial to Evaluate Two Dosing Regimens of Subcutaneous Formulation of Nivolumab in Combination With Intravenous Ipilimumab and Chemotherapy in Participants With Previously Untreated Metastatic or Recurrent NSCLC

The purpose of this study is to evaluate two dosing regimens of subcutaneous Nivolumab in combination with intravenous Ipilimumab and chemotherapy in participants with previously untreated metastatic or recurrent Non-Small Cell Lung Cancer (NSCLC)

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Carboplatin; Drug: Cisplatin; Drug: Paclitaxel; Drug: Pemetrexed; Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-000
    • Local Institution - 0034
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • Local Institution - 0041
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30380-490
      • Local Institution - 0043
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Local Institution - 0038
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Local Institution - 0037
• Chile
  • Santiago Metropolitan
    • Santiago, Santiago Metropolitan, Chile, 8420383
      • Local Institution - 0067
• France
  • Côte-d'Or
    • Dijon, Côte-d'Or, France, 21079
      • Local Institution - 0065
  • Hauts-de-Seine
    • Suresnes, Hauts-de-Seine, France, 92151
      • Local Institution - 0003
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75014
      • Local Institution - 0010
• Greece
  • Attikí
    • Athens, Attikí, Greece, 115 27
      • Local Institution - 0012
    • Chaïdári, Attikí, Greece, 12462
      • Local Institution - 0013
  • Kentrikí Makedonía
    • Thessaloniki, Kentrikí Makedonía, Greece, 540 07
      • Local Institution - 0011
  • Thessalía
    • Larissa, Thessalía, Greece, 41110
      • Local Institution - 0014
• Italy
  • Novara, Italy, 28100
    • Local Institution - 0017
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Local Institution - 0015
  • Friuli Venezia Giulia
    • Udine, Friuli Venezia Giulia, Italy, 33100
      • Local Institution - 0057
  • Lombardy
    • Bergamo, Lombardy, Italy, 24127
      • Local Institution - 0020
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • Local Institution - 0019
• Poland
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 03-411
      • Local Institution - 0081
  • Pomeranian Voivodeship
    • Prabuty, Pomeranian Voivodeship, Poland, 82-550
      • Local Institution - 0080
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 93-338
      • Local Institution - 0079
• Romania
  • Bucharest, Romania, 020335
    • Local Institution - 0075
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0074
  • Iași, Romania, 700483
    • Local Institution - 0078
  • Bucharest
    • Bucharest, Bucharest, Romania, 022328
      • Local Institution - 0073
  • Cluj
    • Florești, Cluj, Romania, 407280
      • Local Institution - 0076
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Local Institution - 0077
• South Africa
  • GP
    • Sandton, GP, South Africa, 2196
      • Local Institution - 0009
  • Gauteng
    • Soweto, Gauteng, South Africa, 2013
      • Local Institution - 0031
  • Western Cape
    • Rondebosch, Western Cape, South Africa, 7700
      • Local Institution - 0084
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Local Institution - 0032
  • California
    • Los Angeles, California, United States, 90033
      • Local Institution - 0062
  • Idaho
    • Boise, Idaho, United States, 83702
      • Local Institution - 0063
    • Boise, Idaho, United States, 83706
      • Local Institution - 0052
    • Post Falls, Idaho, United States, 83854
      • Local Institution - 0064
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution - 0047
    • Cleveland, Ohio, United States, 44109
      • Local Institution - 0033
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Local Institution - 0051

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Participants must have histologically confirmed stage IV or recurrent non-small cell lung cancer (NSCLC) (as defined by the 9th edition of the IASLC Lung Cancer Staging Guidelines) of squamous or non-squamous histology.
• Participants must have no prior systemic anti-cancer treatment (including EGFR, ALK, ROS-1, BRAF, RET, and NTRK inhibitors) given as primary therapy for advanced or metastatic disease.
• Participants with prior definitive chemoradiation for locally advanced disease is permitted as long as the last administration of chemotherapy or radiotherapy (whichever was given last) occurred at least 6 months prior to randomization. Participants with locally advanced disease with recurrence after chemoradiation therapy (stage III disease, specifically refers to patients with no curative options) are eligible to enroll.
• Participants with prior adjuvant or neoadjuvant chemotherapy for early-stage lung cancer are permitted if completed at least 6 months prior to randomization.
• Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1 at screening and confirmed prior to randomization.
• Participants must have measurable disease by CT or MRI per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria with radiographic tumor assessment performed within 28 days of randomization.

Exclusion Criteria

• Participants must not have any prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
• Participants must not have any known driver mutations with available targeted therapy (including but not limited to EGFR mutations, ALK translocations, ROS-1 translocations and known BRAFV600E, that are sensitive to available targeted inhibitor therapy; participants with a known activating RET mutations and NTRK fusion gene alterations).
• Participants must not have any untreated central nervous system (CNS) metastases
• Participants must not have leptomeningeal metastases (carcinomatous meningitis).
• Participants must not have any active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Participants with previous malignancies (except non-melanoma skin cancers, and in situ cancers such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to randomization and no additional therapy is required or anticipated to be required during the study period.
• Participants must not have a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Participants must not have any history of interstitial lung disease or pneumonitis that required oral or IV glucocorticoids to assist with management.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Nivolumab; Specified dose on specified days; Other Names: BMS-986298
Experimental: Arm B	Drug: Carboplatin; Specified dose on specified days; Drug: Cisplatin; Specified dose on specified days; Drug: Paclitaxel; Specified dose on specified days; Drug: Pemetrexed; Specified dose on specified days; Drug: Ipilimumab; Specified dose on specified days; Other Names: Yervoy; Drug: Nivolumab; Specified dose on specified days; Other Names: BMS-986298

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed serum concentration (Cmax) of subcutaneous Nivolumab in serum	Up to 3 weeks
Time to peak concentration (Tmax) of subcutaneous Nivolumab in serum	Up to 3 weeks
Area under the concentration-time curve within a dosing interval (AUC(TAU)) of subcutaneous Nivolumab in serum	Up to 3 weeks
Concentration at the end of a dosing interval (Ctau) of subcutaneous Nivolumab in serum	Up to 3 weeks
Trough observed concentration (Ctrough) of subcutaneous Nivolumab	At Cycle 7 Day 1 (Week 18)

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with AEs leading to discontinuation	Up to approximately 2.5 years
Number of deaths	Up to approximately 2.5 years
Number of participants with adverse events (AEs)	Up to approximately 2.5 years
Number of participants with serious adverse events (SAEs)	Up to approximately 2.5 years
Number of participants with drug related AEs	Up to approximately 2.5 years
Number of participants with Immune Mediated Adverse Events (IMAEs)	Up to approximately 2.5 years
Number of participants with anti-nivolumab antibodies	Up to approximately 2.5 years
Number of participants with anti-ipilimumab antibodies	Up to approximately 2.5 years
Number of participants with neutralizing antibodies	Up to approximately 2.5 years
Cmax of intravenous Ipilimumab in serum	Up to 6 weeks
Tmax of intravenous Ipilimumab in serum	Up to 6 weeks
AUC(TAU) of intravenous Ipilimumab in serum	Up to 6 weeks
Ctau of intravenous Ipilimumab in serum	Up to 6 weeks

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2025
• Primary Completion (Estimated): February 5, 2027
• Study Completion (Estimated): October 25, 2028

Study Registration Dates

• First Submitted: April 25, 2025
• First Submitted That Met QC Criteria: April 25, 2025
• First Posted (Actual): April 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Nivolumab; Ipilimumab; Checkmate-1533; CA2091533
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Nivolumab; Pemetrexed; Ipilimumab; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: CA209-1533

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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