Study of Nivolumab Verses Nivolumab and Ipilimumab Combination in EGFR Mutant Non-small Cell Lung Cancer

NCT03091491 | Terminated Phase 2

• 1 other identifier: CA209-777
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether Nivolumab in combination with Ipilimumab is associated with superior response rate compared to Nivolumab alone in patients with advanced Epidermal Growth Factor Receptor (EGFR) mutation positive Non-small Cell Lung Cancer who have failed one line of standard EGFR tyrosine kinase inhibitor and not more than one line of chemotherapy regimen. This study also aims to determine predictive biomarkers of response/benefit in patients with EGFR mutation positive NSCLC.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  From baseline until best overall response of Complete Response (CR) or Partial Response (PR), up to 2 years

Secondary Outcomes (6)

• Progression-Free Survival

  From time of randomisation until first documented disease progression or death due to any cause, up to 2 years

• Duration of Response

  From time of first response until first documented disease progression or death due to any cause, up to 2 years

• Overall Survival

  From time of randomisation until death due to any cause, up to 2 years

• Evaluate the toxicity profiles of Nivolumab with or without Ipilimumab by measuring the number of participants with treatment-related adverse events

  From the time the Informed Consent Form is signed until at least 100 days after discontinuation of dosing, up to 2 years

• Evaluate capability of the addition of Ipilimumab to patients who progress on Nivolumab alone (Arm A) to achieve clinical benefit by measuring the time taken to achieve CR, PR or Stable Disease (SD)

  From time of first dose of Ipilimumab until best overall response of CR, PR, or SD, up to 2 years

Study Arms (2)

Nivolumab

EXPERIMENTAL

Drug: Nivolumab

Nivolumab and Ipilimumab

EXPERIMENTAL

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

Ipilimumab 1 mg/kg administered every 6 weeks as a 30 min IV infusion

Also known as: Yervoy

Nivolumab and Ipilimumab

Nivolumab DRUG

Nivolumab 3 mg/kg administered every 2 weeks as a 30 min IV infusion

Also known as: Opdivo

Nivolumab; Nivolumab and Ipilimumab

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• i. Signed informed consent
• ii. Male or female, 21 years or older
• Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 5 months (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab
• Women must not be breastfeeding
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception
• WOCBP 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 less than 40 milli-international units per millilitre (mIU/mL).
• Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days.
• iii. Advanced EGFR+ NSCLC
• iv. Eastern Cooperative Oncology Group (ECOG) 0-2 performance status
• v. Progressed on one line of standard EGFR TKI and not more than one line of chemotherapy; 3rd generation EGFR TKI for patients with T790M mutation is allowed
• A 14-day washout period is required for EGFR TKI for patients who received this as the last therapy before recruitment
• A 28-day washout period is required for chemotherapy for patients who received this as the last therapy before recruitment. All drug-related toxicities should have returned to baseline with the exception of neuropathy, fatigue, and alopecia.
• vi. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration
• White Blood Cell (WBC) ≥ 2000/µL

You may not qualify if:

• i. Symptomatic brain or leptomeningeal metastases (patients who have treated stable brain or Leptomeningeal disease are eligible; there is no magnetic resonance imaging (MRI) evidence of progression for \[lowest minimum is 4 weeks or more\] after treatment is complete and within 28 days prior to the first dose of nivolumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration).
• ii. Poor performance status of ECOG 3-4
• iii. Tumour sites not amenable to CT-guided core biopsies or trucut biopsies; However waiver for this criterion can be given for selected patients on a case-by-case basis for patients with sites of disease that are technically difficult to access after discussion with interventional radiologist. Waivers are allowed for not more than 70 patients for this study in order to allow sufficient number of quality tumour biopsies for biomarker analysis in this study. Waivers would have to be approved by the Principal Investigator.
• iv. Unwilling to undergo 2 biopsies and contribute research bloods for the study
• v. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• vi. Concurrent 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.
• vii. Prior treatment with other anti-Programmed cell death protein 1 (anti-PD1) or anti-PDL1 or anti-CTLA4 therapies
• viii. Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to randomization
• Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study.
• Patients with history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments done by MRI.
• The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.
• ix. Active interstitial lung disease or history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan; History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• x. Active tuberculosis
• xi. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• xii. Prior allogeneic bone marrow transplantation or solid organ transplant

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• National University Hospital, Singapore: collaborator
• Johns Hopkins Singapore: collaborator

Study Sites (3)

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Tan Tock Seng Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Ipilimumab; Nivolumab

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

Study Officials

• Eng Huat Tan

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

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: March 6, 2017
• First Posted: March 27, 2017
• Study Start: April 7, 2017
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: June 14, 2022

Record last verified: 2022-06

Locations

SG (3)