Neoadjuvant Nivolumab With CCR2/5-inhibitor or Anti-IL-8) for Non-small Cell Lung Cancer (NSCLC) or Hepatocellular Carcinoma (HCC)

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT04123379

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arms

54.4

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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:

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)
Improvement in long term survival rates

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer Hepatocellular Carcinoma	Drug: Nivolumab Drug: BMS-813160 Drug: BMS-986253	Phase 2

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tisch Cancer Institute - BMS Study # CA027-005: Neoadjuvant Nivolumab + BMS-813160 (CCR2/5-inhibitor) or BMS-986253 (Anti-IL-8) for NSCLC or HCC

Actual Study Start Date :

Mar 19, 2020

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A NSCLC: Nivolumab + BMS-813160	Drug: Nivolumab q4w, dosed twice before surgery and three times following recovery from surgery by injection Drug: BMS-813160 300mg oral twice a day for 28 days Other Names: CCR2/5-inhibitor
Experimental: Cohort B NSCLC: Nivolumab + BMS-986253	Drug: Nivolumab q4w, dosed twice before surgery and three times following recovery from surgery by injection Drug: BMS-986253 2400mg once by injection Other Names: anti-IL-8
Experimental: Cohort C HCC: Nivolumab	Drug: Nivolumab q4w, dosed twice before surgery and three times following recovery from surgery by injection
Experimental: Cohort D HCC: Nivolumab + BMS-813160	Drug: Nivolumab q4w, dosed twice before surgery and three times following recovery from surgery by injection Drug: BMS-813160 300mg oral twice a day for 28 days Other Names: CCR2/5-inhibitor
Experimental: Cohort E HCC: Nivolumab + BMS-986253	Drug: Nivolumab q4w, dosed twice before surgery and three times following recovery from surgery by injection Drug: BMS-986253 2400mg once by injection Other Names: anti-IL-8

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Time to Surgery [2 Years]
Measured as the time in days that elapses between the first dose of neoadjuvant therapy and surgical resection.
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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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