CIMAvax Vaccine, Nivolumab, and Pembrolizumab in Treating Patients With Advanced Non-small Cell Lung Cancer or Squamous Head and Neck Cancer

Stage IV Lung Cancer AJCC v8 Clinical Trial

Official title: A Phase I/II Basket Trial of the EGF Vaccine CIMAvax in Combination With Anti-PD1 Therapy in Patients With Advanced NSCLC or Squamous Head and Neck Cancer

Status Recruiting

Clinical Trial Summary

This phase I/II trial studies the best dose and side effects of recombinant human EGF-rP64K/montanide ISA 51 vaccine (CIMAvax) and nivolumab and to see how well they work in treating patients with non-small cell lung cancer or squamous head and neck cancer that has spread to other places in the body. Vaccine therapy, such as CIMAvax vaccine may help slow down and stop tumor growth. Immunotherapy with monoclonal antibodies, such as nivolumab and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CIMAvax vaccine together with nivolumab or pembrolizumab may work better in treating patients with non-small cell lung cancer or squamous head and neck cancer.

Clinical Trial Description

PRIMARY OBJECTIVES:

• I. To identify the maximum dose of CIMAvax in combination with nivolumab based on dose limiting toxicities (DLTs) as assessed by Common Terminology Criteria for Adverse Events version 4.03 (CTCAE version [v] 4.03). (Phase I)

• II. To evaluate the 12-month overall survival of CIMAvax combined with nivolumab in patients with advanced non-small cell lung cancer (NSCLC). (Phase II-Study A)

• III. To evaluate the 6-month progression free survival (PFS) of CIMAvax combined with nivolumab in patients with advanced recurrent squamous cell carcinoma of the head and neck. (Phase II-Study B)

• IV. To evaluate the objective response rate of pembrolizumab in combination with CIMAvax as first-line therapy in patients with advanced NSCLC (PD-L1 expression >= 50%). (Phase II-Study C)

• V. To evaluate the 12-month PFS of pembrolizumab in combination with CIMAvax as maintenance therapy in patients with advanced squamous NSCLC (PD-L1 expression < 50%) (Phase II-Study D)

• VI. To evaluate the 12-month PFS of pembrolizumab in combination with CIMAvax as maintenance therapy in patients with advanced NON-squamous NSCLC without EGFR/ALK/ROS-1/KRAS mutations (PD-L1 expression < 50%) (Phase II- Study E)

SECONDARY OBJECTIVES

• I. To assess the toxicity of CIMAvax combined with nivolumab using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03). (Phase I)

• II. Determine the preliminary efficacy of the combination of anti-PD1 therapy with CIMAvax. (Phase I) III. To evaluate progression free survival (PFS) for the combination of CIMAvax and nivolumab in patients with advanced NSCLC. (Phase II-Study A) IV. To evaluate the 12-month overall survival of patients with advanced recurrent squamous cell carcinoma of the head and neck who received nivolumab in combination with CIMAvax. (Phase II-Study B)

• V. To evaluate the PFS and 12-month overall survival of CIMAvax in combination with pembrolizumab as first-line therapy in patients with advanced NSCLC (PD-L1 expression >= 50%). (Phase II-Study C)

• VI. To evaluate the PFS and overall survival of CIMAvax in combination with pembrolizumab as maintenance therapy in patients with advanced squamous NSCLC (PD-L1 expression < 50%). (Phase iI- Study D)

• VII. To evaluate the PFS and overall survival of CIMAvax in combination with pembrolizumab as maintenance treatment in non-squamous NSCLC patients without EGFR/ALK/ROS-1/KRAS mutations after induction chemoimmunotherapy (PD-L1 expression < 50%).(Phase II - Study E)

• VIII. To assess the toxicity of CIMAvax combined with nivlumab or pembrolizumab suing the CTEP NCI Common Terminology Criteria for Adverse Events (CTCAE version 4.03). (Phase II)

TERTIARY OBJECTIVES:

I. To conduct correlative studies comparing blood EGF levels, platelet levels, markers of immune response and functionality of antibody response. (Phase I) II. To examine the association of EGFR (total and activated), PD-1 and PD-L1 expression and mutations in tumor tissue with biomarkers of genetic and immune response. (Phase I and II) III. Comparison of response assessment criteria for a prospective analysis (immune-related [ir] Response Evaluation Criteria in Solid Tumors [RECIST] response assessment versus [vs.] immune-related Response Criteria [irRC] vs. RECIST 1.1). (Phase I and II) IV. To characterize the blood EGF levels and other blood-based biomarkers of patients censored from the trial because of low titer response. (Phase II)

OUTLINE: This is a phase I dose escalation study of CIMAvax followed by a phase II study.

LOADING PHASE I: Patients receive CIMAvax intramuscularly (IM) and nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 2 weeks for up to 4 doses in the absence of disease progression or unacceptable toxicity. Within 4 weeks after the 4th dose, patients receive CIMAvax IM at the same time as the next nivolumab dose.

MAINTENANCE PHASE I: Patients who do not experience a DLT receive CIMAvax every 4 weeks and nivolumab every 2 weeks.

PHASE II STUDY A and B: Patients receive CIMAvax IM and nivolumab IV over 60 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for nivolumab repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. Patients in Study A with antibody titer >= 1:4000 at the end of the loading phase may receive CIMAvax IM every 8 or 12 weeks during the maintenance phase.

PHASE II STUDY C: Patients with PD-L1expression >= 50% receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment with CIMAvax repeats every 2 weeks for 4 doses during the loading phase and every 4 weeks during the maintenance phase in the absence of disease progression or unacceptable toxicity. Courses for pembrolizumab repeat every 2 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

PHASE II STUDY D: Patients with PD-L1 expression < 50% after 4 cycles of induction chemotherapy with pembrolizumab, receive CIMAvax IM and pembrolizumab IV over 30 minutes. Treatment repeats every 4 weeks for 2 years in the absence of disease progression or unacceptable toxicity

After completion of study treatment, patients are followed up every 30 days for 120 days. ;

Related Conditions & MeSH terms

• Advanced Head and Neck Squamous Cell Carcinoma
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Lung Neoplasms
• Lung Non-Small Cell Carcinoma
• Metastatic Lung Non-Small Cell Carcinoma
• PD-L1 Positive
• Recurrent Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck
• Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
• Stage III Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8
• Stage IIIC Lung Cancer AJCC v8
• Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck AJCC v8
• Stage IV Lung Cancer AJCC v8
• Stage IVA Lung Cancer AJCC v8
• Stage IVB Lung Cancer AJCC v8
• Unresectable Lung Non-Small Cell Carcinoma

• NCT number: NCT02955290
• Study type: Interventional
• Source: Roswell Park Cancer Institute
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 22, 2016
• Completion date: December 9, 2027