Non-small Cell Lung Cancer, Hepatocellular Carcinoma
Conditions
Keywords
Nivolumab, CCR2/5-inhibitor, anti-IL-8
Brief summary
The purpose of this research study is to study the effect of giving nivolumab with CCR2/5-inhibitor or anti-IL-8 before surgery, and after surgery, with the goal of determining if this medicine results in: 1. A significant immune response against their tumor (which the study team will see in the tumor that is taken out at the time of surgery) 2. Improvement in long term survival rates
Detailed description
Objectives: Cohorts A,B (NSCLC): Primary Objective: Major Pathologic Response (MPR) Secondary Objectives: Time to surgery, tolerability and safety, radiographic response Cohorts C,D,E (HCC): Primary Objective: Significant tumor necrosis (STN) Secondary Objectives: Time to surgery, tolerability and safety, radiographic response Diagnosis and Main Inclusion Criteria: Patients must have disease deemed resectable before enrollment. Study Product: Nivolumab 480mg (q4w, dosed twice before surgery and three times following recovery from surgery) BMS-813160 (CCR2/5-inhibitor) 300mg oral twice a day for 28 days BMS-986253 (anti-IL-8) 2400mg once
Interventions
DRUGNivolumab
q4w, dosed twice before surgery and three times following recovery from surgery by injection
DRUGBMS-813160
300mg oral twice a day for 28 days
DRUGBMS-986253
2400mg once by injection
Sponsors
Bristol-Myers Squibb
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of NSCLC or HCC * Willing to provide blood samples * Willing to undergo leukapheresis at Mount Sinai Hospital or New York Blood Bank * Willing to have excisional or core needle biopsies * At least 18 years of age * ECOG 0-1 * Surgical candidate for resection of their tumor * Agree to use adequate contraception * Adequate organ and marrow function
Exclusion criteria
* Patients who have had chemotherapy or radiotherapy within 4 months for a different primary tumor or patients who have received locoregional therapy for the target lesion * Patients receiving any other investigational agents * Patients with metastatic disease for whom the intent of surgery would not be curative * Uncontrolled intercurrent illness * Pregnant or nursing * Has a diagnosis of primary immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days * Has active autoimmune disease that has required systemic treatment in the past year * Has a known additional malignancy that is progressing and/or requires active treatment * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not the in the best interest of the patient to participate * HIV positive with detectable viral load or anyone not on stable anti-viral regimen * Has known active Hepatitis B * History of allogeneic hematopoietic cell transplantation or solid organ transplantation * Documented allergic or hypersensitivity response to any protein therapeutics * Patients may not have prolonged QRS or QTc
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response (MPR) | 2 Years | MPR is defined as \<10% viable tumor within resection, at time of surgery. |
| Significant Tumor Necrosis (STN) | 2 Years | STN is defined as necrosis of \>70% of tumor base on pathologic analysis of gross tumor resection at time of surgery. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of individuals who experience radiographic response | 2 Years | As per RECIST v1.1 as determined by pre-surgical imaging, following receipt of the neoadjuvant therapy. For NSCLC this will be based on CT imaging, while for HCC this imaging will be based on MRI radiographic post-contract subtraction. |
| Time to Surgery | 2 Years | Measured as the time in days that elapses between the first dose of neoadjuvant therapy and surgical resection. |
| Overall Survival (OS) | 2 Years | Defined as the time, in days, between treatment initiation and when the patient dies from any cause regardless of etiology. |
| Progression-free survival (PFS) | 2 Years | Defined as the time, in days, between treatment initiation and when the patient is found to have recurrent and/or metastatic disease on imaging, or death for any reason. |
| Percent of individuals who experience adverse events | 2 Years | Safety and Tolerability defined by the percent of individuals who experience adverse events at any point during the neoadjuvant period, or within 30 days following the final dose of nivolumab received. |
Countries
United States
Outcome results
None listed