NCT02947386

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

A Phase I/II Open-Label Study of Nimotuzumab in Combination With Nivolumab in Patients With Advanced Non-small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Roswell Park Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the dose-limiting toxicities (DLT) and estimate the maximum tolerated dose (MTD) of nimotuzumab combined with nivolumab in the therapy of advanced non-small cell lung cancer (NSCLC) in order to establish the recommended phase II dose (RP2D). (Phase I) II. To evaluate the 12 month overall survival of nimotuzumab in combination with nivolumab in patients with advanced NSCLC. (Phase II) SECONDARY OBJECTIVES: I. Examine the safety and tolerability profile of nivolumab in combination with nimotuzumab in NCSLC . (Phase I) II. To evaluate the safety and the tolerability of nimotuzumab in combination with nivolumab using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.0). (Phase I) III. Determine the immune analysis profile of nivolumab in combination with nimotuzumab. (Phase I) IV. Examine the efficacy of the study combination utilizing irRECIST guidelines. (Phase I) V. Overall response rate (ORR) per the immune-related Response Evaluation Criteria in Solid Tumors irRECIST. (Phase I) VI. Progression-free survival (PFS) rate at 1 year. (Phase I) VII. Progression-free survival (PFS). (Phase I) VIII. Overall survival (OS). (Phase I) IX. Disease control rate (DCR) and stable disease (SD). (Phase I) X. To evaluate the safety profile of Nimotuzaumab in combination with Nivolumab in NCSLC using the CTCAE V. 4. XI.To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: overall response rate (ORR) per irRECIST. (Phase II) XII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: progression-free survival (PFS) rate at 1 year. (Phase II) XIII. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: progression-free survival (PFS). (Phase II) XIV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: overall survival (OS). (Phase II) XV. To evaluate the efficacy of nimotuzumab in combination with nivolumab in patients with advanced NSCLC compared to historic outcomes of nivolumab alone, as determined by secondary measures of efficacy, including: disease control rate (DCR) and stable disease (SD). (Phase II) TERTIARY OBJECTIVES: I. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and adverse events (AE). (Phase I) II. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels; PD-L1 expression within both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase I) III. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase I) IV. Examine the relationship of EGFR expression in tissue to PFS, OS, ORR and AE. (Phase II) V. Examine the relationship of infiltrating CD4+ and CD8+ T cells and other immune and genetic markers, and their associated PD-1, CD45RA or CD45RO levels. (Phase II) VI. Examine the relationship of PD-L1 expression within both neoplastic and non-neoplastic stromal elements of the tumor microenvironment to PFS, OS, ORR and AE. (Phase II) VII. Comparison of response assessment criteria for a prospective analysis; irRECIST response assessment; irRC. (Phase II) OUTLINE: This is a phase I, dose-escalation study of nimotuzumab followed by a phase II study. Patients receive nivolumab intravenously (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. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.

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

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Nimotuzumab	Given IV
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2017-06-29
• Primary completion: 2021-04-15
• Completion: 2022-09-08
• First posted: 2016-10-27
• Last updated: 2023-10-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study