Clinical trial NCT06946797: 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)
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Nivolumab
Ipilimumab
Checkmate-1533
CA2091533
NSCLC
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-04-27
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum observed serum concentration (Cmax) of subcutaneous Nivolumab in serum
timeFrame: Up to 3 weeks
measure: Time to peak concentration (Tmax) of subcutaneous Nivolumab in serum
timeFrame: Up to 3 weeks
measure: Area under the concentration-time curve within a dosing interval (AUC(TAU)) of subcutaneous Nivolumab in serum
timeFrame: Up to 3 weeks
measure: Concentration at the end of a dosing interval (Ctau) of subcutaneous Nivolumab in serum
timeFrame: Up to 3 weeks
measure: Trough observed concentration (Ctrough) of subcutaneous Nivolumab
timeFrame: At Cycle 7 Day 1 (Week 18)
Secondary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Up to approximately 2.5 years
measure: Number of participants with serious adverse events (SAEs)
timeFrame: Up to approximately 2.5 years
measure: Number of participants with drug related AEs
timeFrame: Up to approximately 2.5 years
measure: Number of participants with Immune Mediated Adverse Events (IMAEs)
timeFrame: Up to approximately 2.5 years
measure: Number of participants with AEs leading to discontinuation
timeFrame: Up to approximately 2.5 years
measure: Number of deaths
timeFrame: Up to approximately 2.5 years
measure: Number of participants with anti-nivolumab antibodies
timeFrame: Up to approximately 2.5 years
measure: Number of participants with anti-ipilimumab antibodies
timeFrame: Up to approximately 2.5 years
measure: Number of participants with neutralizing antibodies
timeFrame: Up to approximately 2.5 years
measure: Cmax of intravenous Ipilimumab in serum
timeFrame: Up to 6 weeks
measure: Tmax of intravenous Ipilimumab in serum
timeFrame: Up to 6 weeks
measure: AUC(TAU) of intravenous Ipilimumab in serum
timeFrame: Up to 6 weeks
measure: Ctau of intravenous Ipilimumab in serum
timeFrame: Up to 6 weeks
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Local Institution - 0032
state: Alaska
city: Los Angeles
country: United States
facility: Local Institution - 0062
state: California
city: Boise
country: United States
facility: Local Institution - 0063
state: Idaho
city: Boise
country: United States
facility: Local Institution - 0052
state: Idaho
city: Post Falls
country: United States
facility: Local Institution - 0064
state: Idaho
city: Cleveland
country: United States
facility: Local Institution - 0047
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0033
state: Ohio
city: Allentown
country: United States
facility: Local Institution - 0051
state: Pennsylvania
city: Brasilia
country: Brazil
facility: Local Institution - 0041
state: Distrito Federal
city: Porto Alegre
country: Brazil
facility: Local Institution - 0038
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Local Institution - 0037
state: São Paulo
city: São Paulo
country: Brazil
facility: Local Institution - 0034
city: Antofagasta
country: Chile
facility: Local Institution - 0068
state: AN
city: Santiago
country: Chile
facility: Local Institution - 0067
state: Región Metropolitana De Santiago
city: Viña del Mar
country: Chile
facility: Local Institution - 0069
state: Valparaíso
city: Dijon
country: France
facility: Local Institution - 0065
state: Côte-d'Or
city: Suresnes
country: France
facility: Local Institution - 0003
state: Hauts-de-Seine
city: Paris
country: France
facility: Local Institution - 0010
state: Île-de-France
city: Athens
country: Greece
facility: Local Institution - 0012
state: Attikí
city: Chaidari
country: Greece
facility: Local Institution - 0013
state: Attikí
city: Thessaloniki
country: Greece
facility: Local Institution - 0011
state: Kentrikí Makedonía
city: Larissa
country: Greece
facility: Local Institution - 0014
state: Thessalía
city: Meldola
country: Italy
facility: Local Institution - 0015
state: Emilia-Romagna
city: Udine
country: Italy
facility: Local Institution - 0057
state: Friuli-Venezia Giulia
city: Bergamo
country: Italy
facility: Local Institution - 0020
state: Lombardia
city: Firenze
country: Italy
facility: Local Institution - 0019
state: Toscana
city: Novara
country: Italy
facility: Local Institution - 0017
city: Guadalajara
country: Mexico
facility: Local Institution - 0025
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution - 0058
state: Nuevo León
city: Merida
country: Mexico
facility: Local Institution - 0027
state: Yucatán
city: Mexico
country: Mexico
facility: Local Institution - 0024
city: Puebla
country: Mexico
facility: Local Institution - 0022
city: Warszawa
country: Poland
facility: Local Institution - 0081
state: Mazowieckie
city: Prabuty
country: Poland
facility: Local Institution - 0080
state: Pomorskie
city: Łódź
country: Poland
facility: Local Institution - 0079
state: Łódzkie
city: Bucharest
country: Romania
facility: Local Institution - 0075
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0073
state: București
city: Florești
country: Romania
facility: Local Institution - 0076
state: Cluj
city: Craiova
country: Romania
facility: Local Institution - 0077
state: Dolj
city: Cluj
country: Romania
facility: Local Institution - 0074
city: Iași
country: Romania
facility: Local Institution - 0078
city: Pretoria
country: South Africa
facility: Local Institution - 0066
state: Gauteng
city: Soweto
country: South Africa
facility: Local Institution - 0031
state: Gauteng
city: Sandton
country: South Africa
facility: Local Institution - 0009
state: GP
city: Rondebosch
country: South Africa
facility: Local Institution - 0084
state: Western Cape
city: Adana
country: Turkey
facility: Local Institution - 0070
city: Ankara
country: Turkey
facility: Local Institution - 0072
city: Istanbul
country: Turkey
facility: Local Institution - 0071
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: