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

Phase 2
Active, not recruiting
Conditions
Non-small Cell Lung Cancer
Hepatocellular Carcinoma
Interventions
Registration Number
NCT04123379
Lead Sponsor
Icahn School of Medicine at Mount Sinai
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

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
48
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort BBMS-986253NSCLC: Nivolumab + BMS-986253
Cohort EBMS-986253HCC: Nivolumab + BMS-986253
Cohort CNivolumabHCC: Nivolumab
Cohort ANivolumabNSCLC: Nivolumab + BMS-813160
Cohort BNivolumabNSCLC: Nivolumab + BMS-986253
Cohort ABMS-813160NSCLC: Nivolumab + BMS-813160
Cohort ENivolumabHCC: Nivolumab + BMS-986253
Cohort DBMS-813160HCC: Nivolumab + BMS-813160
Cohort DNivolumabHCC: Nivolumab + BMS-813160
Primary Outcome Measures
NameTimeMethod
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.

Major Pathologic Response (MPR)2 Years

MPR is defined as \<10% viable tumor within resection, at time of surgery.

Secondary Outcome Measures
NameTimeMethod
Percent of individuals who experience adverse events2 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.

Time to Surgery2 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.

Percent of individuals who experience radiographic response2 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.

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai

🇺🇸

New York, New York, United States

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