Nimotuzumab and Nivolumab in Treating Patients With Advanced Non-small Cell Lung Cancer

NCT02947386 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: I 281616NCI-2016-01476
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the best dose and side effects of nimotuzumab when giving together with nivolumab and to see how well they work in treating patients with non-small cell lung cancer that has spread to other places in the body and usually cannot be cured or controlled with treatment. Monoclonal antibodies, such as nimotuzumab and nivolumab, may block tumor growth in different ways by targeting certain cells.

Conditions

EGFR Gene Mutation; Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• DLT as graded by NCI CTCAE version 4.0 (Phase I)

  No formal analyses of DLTs are planned. Participants who do not have a DLT and who do not complete a full cycle of treatment will be considered non-evaluable for DLT.

  Up to 28 days

• ORR defined as complete response (CR) + partial response (PR) divided by number of patients as assessed by RECIST version 1.1 (Phase II)

  Will be calculated as the number of patients with a confirmed complete or partial response divided by the total number of patients. The 95% confidence interval for ORR (CR + PR) will be presented based on the Wilson Score method as irRC response.

  Up to 3 years

Secondary Outcomes (1)

• Incidence of adverse events assessed by NCI CTCAE version 4.0 (Phase I and II)

  Up to 30 days after the last dose of study treatment

Other Outcomes (2)

• EGFR expression in tumor tissue (Phase I and II)

  Up to 3 years

• PD-L1 expression in tumor tissue (Phase I and II)

  Up to 3 years

Study Arms (1)

Treatment (nivolumab, nimotuzumab)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes and nimotuzumab IV over 60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Nimotuzumab; Biological: Nivolumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (nivolumab, nimotuzumab)

Nimotuzumab BIOLOGICAL

Given IV

Also known as: Thera-CIM-hr3, TheraCim hR3, Theraloc

Treatment (nivolumab, nimotuzumab)

Nivolumab BIOLOGICAL

Given IV

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

Treatment (nivolumab, nimotuzumab)

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Patients with pathologically confirmed non-small cell lung cancer
• Patients must have had progressive NSCLC after first-line platinum-based chemotherapy for advanced disease
• Have at least 3 months life expectancy
• Have measurable disease per RECIST 1.1 criteria present
• Patients with adenocarcinoma known to have anaplastic lymphoma kinase (ALK) rearrangements and/or epidermal growth factor receptor (EGFR) mutations that have had prior EGFR or ALK tyrosine kinase inhibitor therapy and have progressed, will also be eligible, regardless of line of therapy
• Phase I optional archival tissue/phase II mandatory archival tissue: able to provide enough biopsy tissue samples including primary diagnostic biopsy (archival), re-biopsy tissues (archival from time of disease progression/recurrence following first-line treatment failure) at disease progression to determine PD-L1 and EGFR expression and other biomarkers
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Serum creatinine =\< 1.5 x institution upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 1.5 x ULN or =\< 5 x ULN if liver metastases are present
• Total serum bilirubin =\< ULN; or total bilirubin =\< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's syndrome
• Troponin-I, CK-MB +\< BNP \<200pg/ml
• LVEF \>= LLN

You may not qualify if:

• Active autoimmune disease that has required systemic treatment in past 2 years; use of inhaled corticosteroids is allowed
• Phase II only: history of other malignancies are allowed as long as the current disease stage that did not require active treatment with concomitant systemic cytotoxic chemotherapy, targeted therapy, investigational or biologic therapy (e.g., anti-CTLA4 or HER2 monoclonal antibodies) within 12 months prior to study registration and, is not likely to require systemic therapy in the next 12 months; hormone-related therapies (e.g., somatostatin analogues, etc.) are allowed on a case-to-case basis upon discussion with principal investigator
• Active clinically serious infections requiring antibiotics, antiviral or antifungal agents
• Symptomatic brain metastases; uncontrolled pleural effusion, seroperitoneum, or pericardial effusion
• Has had any major surgery, chemotherapy, or radiotherapy within the previous 4 weeks; gamma knife radiosurgery for brain metastases within less than 2 weeks
• Receiving other anti-cancer medical treatment during the study outside of the nimotuzumab or nivolumab
• Clinically significant interstitial pulmonary disease or known diagnosis of interstitial lung disease (ILD)
• Has known immunosuppressive disease (e.g. human immunodeficiency virus \[HIV\], acquired immune deficiency syndrome \[AIDS\])
• Patient has known hypersensitivity to the components of the study drugs or their analogs
• Patient with uncontrolled cardiac disease or cardiac dysfunction, including any of the following:
• History of uncontrolled angina pectoris that does not respond to medical intervention
• Symptomatic pericarditis or myocardial infarction within 12 months prior to study entry that did not respond to treatment
• History of documented congestive heart failure (New York Heart Association functional classification III or IV)
• Documented cardiomyopathy
• Uncontrolled hypertension defined by: systolic blood pressure (SBP) \>= 160 mmHg and/or diastolic blood pressure (DBP) \>= 100 mmHg

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

nimotuzumab; TheraCIM; 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

• Grace Dy

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2016
• First Posted: October 27, 2016
• Study Start: June 29, 2017
• Primary Completion: April 15, 2021
• Study Completion: September 8, 2022
• Last Updated: October 5, 2023

Record last verified: 2023-10

Locations

US (1)