Nivolumab With or Without Ipilimumab or Chemotherapy in Treating Patients With Previously Untreated Stage I-IIIA Non-small Cell Lung Cancer

NCT03158129 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016-0982NCI-2018-01210
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well nivolumab works when given alone and in combination with ipilimumab or chemotherapy in treating patients with previously untreated stage I-IIIA non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin, docetaxel, and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab with ipilimumab or chemotherapy may work better in treating patients with non-small cell lung cancer compared to chemotherapy alone.

Conditions

Stage I Lung Non-Small Cell Cancer AJCC v7; Stage IA Lung Non-Small Cell Carcinoma AJCC v7; Stage IB Lung Non-Small Cell Carcinoma AJCC v7; Stage II Lung Non-Small Cell Cancer AJCC v7; Stage IIA Lung Non-Small Cell Carcinoma AJCC v7; Stage IIB Lung Non-Small Cell Carcinoma AJCC v7; Stage IIIA Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (mPR)

  The percentage of viable tumor cells was averaged across all reviewed tumor slides from the lung resection specimen. The specimen was reviewed by two pathologists and average score was used. Tumors with ≤ 10% of viable tumor cells were considered to have undergone MPR. Patients who did not have surgery was considered to be no MPR.

  The lung resection specimen was collected at surgery.

Secondary Outcomes (7)

• Pathologic Complete Response (pCR)

  The lung resection specimen was collected at surgery.

• Radiographic Response

  Reassessment after induction therapy

• Overall Survival (OS)

  In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively

• Event-free Survival (EFS)

  In Arms A and B, the cutoff date was 2020-2-25. The median follow-up time frame was 22.2 months. In Arms C and D, the cutoff date was 2022-7-18. The median follow-up time frames were 39.2 and 24.0 months respectively.

• Residual Tumor Classification

  At surgery

Study Arms (4)

Arm A (nivolumab)

EXPERIMENTAL

Participants receive nivolumab IV over 60 minutes on days 1, 15, and 29 in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab

Arm B (nivolumab, ipilimumab)

EXPERIMENTAL

Participants receive nivolumab as in Arm A and receive ipilimumab IV over 90 minutes on day 1 in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab

Arm C (nivolumab, cisplatin, docetaxel, pemetrexed)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes and cisplatin IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

Drug: Cisplatin; Drug: Docetaxel; Biological: Nivolumab; Drug: Pemetrexed

Arm D (ipilimumab, nivolumab, chemotherapy)

EXPERIMENTAL

Patients receive ipilimumab IV over 90 minutes on day 1, nivolumab IV over 30 minutes on days 1, 22, and 43, and cisplatin (or carboplatin) IV over 2 hours on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity. Patients also receive docetaxel IV over 1 hour or pemetrexed IV over 10 minutes on days 1, 22, and 43 in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Biological: Ipilimumab; Biological: Nivolumab; Drug: Pemetrexed

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm D (ipilimumab, nivolumab, chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone''s Chloride, Peyrone''s Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm C (nivolumab, cisplatin, docetaxel, pemetrexed); Arm D (ipilimumab, nivolumab, chemotherapy)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Arm C (nivolumab, cisplatin, docetaxel, pemetrexed); Arm D (ipilimumab, nivolumab, chemotherapy)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm B (nivolumab, ipilimumab); Arm D (ipilimumab, nivolumab, chemotherapy)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm A (nivolumab); Arm B (nivolumab, ipilimumab); Arm C (nivolumab, cisplatin, docetaxel, pemetrexed); Arm D (ipilimumab, nivolumab, chemotherapy)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Arm C (nivolumab, cisplatin, docetaxel, pemetrexed); Arm D (ipilimumab, nivolumab, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed previously untreated non-small cell lung cancer. If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected lung cancer are eligible, but pathology must be confirmed prior to initiating treatment on study. Neuroendocrine carcinomas are not eligible. Carcinomas with neuroendocrine differentiation are eligible
• Patients with stage IA or stage IB \< 4 cm (according to American Joint Committee on Cancer \[AJCC\] 7th edition) are eligible for randomization into arms A and B only. Patients with stage IB \>= 4 cm, IIA, IIB, or IIIA disease (according to AJCC 7th edition) are eligible for randomization into arms A, and B, and for enrollment into arms C and D
• Patients with stage IIIA must not have more than one mediastinal lymph node station involved by tumor
• All patients must have lymph node evaluation of contralateral stations 2 and/or 4 to exclude N3 disease
• The patient must be a suitable candidate for surgery, in the opinion of the treating physician
• Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin \>= 8.0 g/dL
• Platelets \>= 100 x 10\^9/L
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL)
• Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min

You may not qualify if:

• Prior systemic therapy or radiation therapy for treatment of the current lung cancer
• Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug
• Pregnant or lactating female: Women of childbearing potential (WOCB) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 72 hours prior to the start of nivolumab; Women of childbearing potential is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes
• Unwillingness or inability to follow the procedures required in the protocol
• Patients with pre-existing sensorineural hearing impairment/loss or newly diagnosed as documented by an audiology assessment performed prior to study enrollment may not be eligible for cisplatin and may be dispositioned to carboplatin, as determined by the treating physician.
• Patients with a history of severe hypersensitivity reaction to taxotere and or polysorbate 80 must be excluded
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Subjects with active, known or suspected autoimmune disease. Subjects with 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 are permitted to enroll
• Subjects with 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. Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if \> 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Prior treatment with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibody
• Known positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid indicating acute or chronic infection
• Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
• History of severe hypersensitivity reaction to any monoclonal antibody and/or to study drug components
• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
• Patients who are sexually active, with preserved reproductive capacity, and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during and after the trial

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

• Cascone T, Leung CH, Weissferdt A, Pataer A, Carter BW, Godoy MCB, Feldman H, William WN Jr, Xi Y, Basu S, Sun JJ, Yadav SS, Rojas Alvarez FR, Lee Y, Mishra AK, Chen L, Pradhan M, Guo H, Sinjab A, Zhou N, Negrao MV, Le X, Gay CM, Tsao AS, Byers LA, Altan M, Glisson BS, Fossella FV, Elamin YY, Blumenschein G Jr, Zhang J, Skoulidis F, Wu J, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Rajaram R, Antonoff MB, Fujimoto J, Solis LM, Parra ER, Haymaker C, Wistuba II, Swisher SG, Vaporciyan AA, Lin HY, Wang J, Gibbons DL, Jack Lee J, Ajami NJ, Wargo JA, Allison JP, Sharma P, Kadara H, Heymach JV, Sepesi B. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial. Nat Med. 2023 Mar;29(3):593-604. doi: 10.1038/s41591-022-02189-0. Epub 2023 Mar 16.

  PMID: 36928818 DERIVED

• Cascone T, Weissferdt A, Godoy MCB, William WN Jr, Leung CH, Lin HY, Basu S, Yadav SS, Pataer A, Mitchell KG, Khan MAW, Shi Y, Haymaker C, Solis LM, Parra ER, Kadara H, Wistuba II, Sharma P, Allison JP, Ajami NJ, Wargo JA, Jenq RR, Gibbons DL, Lee JJ, Swisher SG, Vaporciyan AA, Heymach JV, Sepesi B. Nodal immune flare mimics nodal disease progression following neoadjuvant immune checkpoint inhibitors in non-small cell lung cancer. Nat Commun. 2021 Aug 19;12(1):5045. doi: 10.1038/s41467-021-25188-0.

  PMID: 34413300 DERIVED

• Cascone T, William WN Jr, Weissferdt A, Leung CH, Lin HY, Pataer A, Godoy MCB, Carter BW, Federico L, Reuben A, Khan MAW, Dejima H, Francisco-Cruz A, Parra ER, Solis LM, Fujimoto J, Tran HT, Kalhor N, Fossella FV, Mott FE, Tsao AS, Blumenschein G Jr, Le X, Zhang J, Skoulidis F, Kurie JM, Altan M, Lu C, Glisson BS, Byers LA, Elamin YY, Mehran RJ, Rice DC, Walsh GL, Hofstetter WL, Roth JA, Antonoff MB, Kadara H, Haymaker C, Bernatchez C, Ajami NJ, Jenq RR, Sharma P, Allison JP, Futreal A, Wargo JA, Wistuba II, Swisher SG, Lee JJ, Gibbons DL, Vaporciyan AA, Heymach JV, Sepesi B. Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial. Nat Med. 2021 Mar;27(3):504-514. doi: 10.1038/s41591-020-01224-2. Epub 2021 Feb 18.

  PMID: 33603241 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Docetaxel; Ipilimumab; CTLA-4 Antigen; Nivolumab; Pemetrexed

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)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Tina Cascone, MD
• Organization: MD Anderson Cancer Center

tcascone@mdanderson.org

713-792-6363

Study Officials

• Tina Cascone

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 17, 2017
• Study Start: June 16, 2017
• Primary Completion: November 13, 2024
• Study Completion: November 13, 2024
• Last Updated: March 5, 2025
• Results First Posted: March 5, 2025

Record last verified: 2025-02

Locations

US (1)