Nivolumab Plus Cisplatin/Pemetrexed or Cisplatin/Gemcitabine as Induction in Resectable Non-Small Cell Lung Cancer

NCT03366766 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 17P.556JT 11371
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in treating patients with stage I-IIIA non-small cell lung cancer that can be removed by surgery. Monoclonal antibodies, such as Nivolumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as Cisplatin and Pemetrexed Disodium or Gemcitabine Hydrochloride, 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, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride may work better in treating patients with non-small cell lung cancer.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Major Pathologic Response (mpCR) Defined as < 10% Viable Tumor

  For the primary endpoint, the major pathologic response rate was calculated as a percentage of patients who achieved a major pathologic response (i.e., \<10% viable tumor) or pathologic complete response. Then, the major pathologic response rate was tested with the exact binomial test under the null hypothesis that the true major pathologic response rate is ≤ 0.19. The corresponding 95% Clopper-Pearson confidence limits were reported too.

  Up to 63 days

Secondary Outcomes (6)

• Number of Adverse Events

  Up to 6 months

• Progression Free Survival

  At 1 year

• Overall Survival

  Up to 1 year

• Overall Clinical Response

  At Week 10

• Overall Clinical Response

  At Month 3

Study Arms (2)

Cohort I (nivolumab, cisplatin, pemetrexed disodium)

EXPERIMENTAL

Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity

Biological: Nivolumab; Drug: Cisplatin; Drug: Pemetrexed Disodium

Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)

EXPERIMENTAL

Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Drug: Gemcitabine Hydrochloride

Interventions

Nivolumab BIOLOGICAL

Given IV

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

Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride); Cohort I (nivolumab, cisplatin, pemetrexed disodium)

Cisplatin DRUG

Given IV

Also known as: (SP-4-2)-Diamminedichloroplatinum, Abiplatin, Blastolem, Briplatin, (CDDP) Cis-diammine-dichloroplatinum, Cis-dichloroammine Platinum (II), Metaplatin, Plastistil, Platinol, Platinex, Platinol-AQ VHA Plus, Peyrone's Salt

Cohort I (nivolumab, cisplatin, pemetrexed disodium)

Pemetrexed Disodium DRUG

Given IV

Also known as: Alimta, N-[4-[2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic Acid Disodium Salt

Cohort I (nivolumab, cisplatin, pemetrexed disodium)

Gemcitabine Hydrochloride DRUG

Given IV

Also known as: Hydrochloride, Difluorodeoxycytidine Hydrochloride, Gemzar

Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed non small cell lung cancer (NSCLC), not previously treated, with a plan to undergo surgery
• Stage I-IIIA (stage I tumors must be \>= 4 cm) per AJCC 8th edition
• Tumor sample must be available for PD-L1 testing; archival tissue within 3 months of study enrollment will be used; if archival tissue is unavailable, a fresh biopsy will be taken
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• While blood cells 2000/ul or more
• Absolute neutrophil count 1500/ul or more
• Platelets 100,000/ul or more
• Hemoglobin 9 g/dl or more; (transfusion permitted)
• Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin \< 3 mg/dl)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
• Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x (ULN) upper limit of normal
• Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 21 days of the study enrollment
• Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive 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; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level more than 40 mIU/mL
• Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic do not require contraception
• All subjects must be able to comprehend and sign a written informed consent document

You may not qualify if:

• Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment
• Any prior radiotherapy to the lung
• Any prior treatment for NSCLC
• Epidermal growth factor receptor (EGFR) or alkaline phosphatase (ALK) activating alteration
• Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Any history of a sever hypersensitivity reaction to any monoclonal antibody
• Any history of allergy to the study drug components
• Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post-diagnosis
• Participants with an active autoimmune disease or any other condition requiring systemic treatment with either corticosteroids within 14 days (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active 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.• Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis. Patients with a history of interstitial lung disease or non-infectious pneumonitis requiring treatment with steroids are also excluded.
• Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
• Patients who have received a live vaccine within 30 days prior initiation of the systemic regimen
• Patients must not be receiving any other investigational agents
• Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial
• Women must not be pregnant (as above) or breastfeeding

Sponsors & Collaborators

• Bristol-Myers Squibb: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University: lead

Study Sites (2)

Abington Hospital - Jefferson Health

Abington, Pennsylvania, 19001, United States

Location

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Pemetrexed; Gemcitabine

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Rita Axelrod, MD
• Organization: Thomas Jefferson University

rita.axelrod@jefferson.edu

215-955-8875

Study Officials

• Rita Axelrod, MD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 8, 2017
• Study Start: December 20, 2017
• Primary Completion: December 6, 2020
• Study Completion: February 8, 2023
• Last Updated: February 20, 2026
• Results First Posted: February 20, 2026

Record last verified: 2026-02

Locations

US (2)