Nivolumab Combined With BMS-986253 in HCC Patients

A Phase II, Randomized, Controlled Trial of Nivolumab in Combination With BMS-986253 in Advanced Hepatocellular Carcinoma (HCC) Patients

A phase II clinical trial is utilized to examine whether BMS-986253 (25 subjects) or Cabiralizumab (25 subjects) when combined with Nivolumab offers improved radiographic objective response rates (ORR) over Nivolumab monotherapy (25 subjects) in advanced HCC patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Nivolumab 240 mg IV every 2 weeks; Drug: Nivolumab 240 mg IV every 2 weeks + BMS-986253 1200 mg IV every 2 weeks; Drug: Nivolumab 240 mg IV every 2 weeks + Cabiralizumab 4 mg/kg IV every 2 weeks

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have histologically confirmed evidence of HCC, Childs-Pugh score of ≤7.

   a. Participants must be willing to provide specimen from fresh, pre- and on-treatment tumor core biopsies for histologic diagnosis and translational studies.

2. Radiographically measurable disease by RECIST1.1 in at least one site.
3. Deemed to not be a candidate for resection or other local-regional therapy.

4. Must not be receiving treatment with other investigational agents and must not have received any other systemic therapy prior to registration.

   a. Prior radioembolization, local ablative therapies (radiofrequency, microwave or cryoablation), radiation (external beam or stereotactic), or hepatic resection permitted if completed ≥ 4 weeks prior to study enrollment and if patient has recovered with ≤ grade 1 toxicity and if untreated measurable disease is present.

5. Be willing and able to provide written informed consent/assent for the trial.
6. Participants must be ≥ 18 years
7. Have a Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
8. If hepatitis B is present, participants must be on anti-viral HBV therapy.
9. All women of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 24 hours prior to start of study treatment
10. All women of childbearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study treatment (s) and for 5 months following discontinuation of study treatment.
11. Males who are sexually active with women of childbearing potential must agree to follow instructions for method (s) of contraception for the duration of treatment with study treatment and for 7 months following discontinuation of study treatment. Additionally, male participants must not donate sperm during this period.
12. Demonstrate adequate organ function as defined by the following required lab and acceptable range criteria:

Adequate bone marrow function:

Absolute neutrophil count > 1000/mcL Platelet count > 50,000/mcL Hemoglobin > 8.5 g/dL

Adequate hepatic function:

Total bilirubin < 2 mg/dL or < 1.5 times upper limit of normal (ULN) AST and ALT < 5 times ULN INR < 1.5 times ULN Albumin > 2.8 g/dL

Adequate renal function:

Creatinine < 2.0 mg/Dl

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. Presence of other malignancies. Participants with active second malignancy other than non-melanoma skin cancer or cervical carcinoma in situ. NOTE: Patients with history of malignancy are not considered to have a "currently active" malignancy if they have completed therapy and are now considered by their physician to be at less than 30% risk for relapse.
3. Have active or history of Tuberculosis
4. Participants with known HIV positive status
5. Participants with known CNS metastases
6. Uncontrolled ascites
7. Uncontrolled encephalopathy
8. Uncontrolled gastro-esophageal varicesPrior organ allograft or allogeneic bone marrow transplantation
9. Participants with active, known, or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid participants with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to first dose of study treatment), psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
10. Participants with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration except for adrenal replacement steroid doses > 10 mg daily prednisone equivalent in the absence of active autoimmune disease. Note: Treatment with a short course of steroids (< 5 days) up to 7 days prior to initiating study treatment is permitted.
11. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity.

12. Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:

    • Myocardial infarction or stroke/transient ischemic attack within the past 6 months
    • Uncontrolled angina within the past 3 months
    • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes)
    • History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III to IV, pericarditis, significant pericardial effusion, or myocarditis)
    • Cardiovascular disease-related requirement for daily supplemental oxygen therapy.
13. Participants with ongoing or active, uncontrolled infections (afebrile for ≥ 48 hours off antibiotics). If hepatitis B is present, must be on anti-viral HBV therapy.
14. Must not have a psychiatric illness, other significant medical illness, or social situation which, in the investigator's opinion, would limit compliance or ability to comply with study requirements.
15. Any major surgery within 4 weeks of study treatment. Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before
16. Any uncontrolled inflammatory disease including Crohn's disease and ulcerative colitis
17. Treatment with botanical preparations (eg, herbal supplements, including potential drugs of abuse, or traditional Chinese medicines) intended for general health support or to treat the disease under study within 2 weeks prior to randomization/treatment.
18. Concomitant use of statins while on study.
19. Current or history of clinically significant muscle disorders (eg, myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels.
20. Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and Tween 80 (polysorbate 80).
21. Participants who have received a live / attenuated vaccine within 30 days of first treatment.
22. Concomitant use of any live / attenuated vaccine during treatment and until 100 days following last dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nivolumab Monotherapy	Drug: Nivolumab 240 mg IV every 2 weeks; Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy
Experimental: Nivolumab/BMS-986253 combination	Drug: Nivolumab 240 mg IV every 2 weeks; Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy; Drug: Nivolumab 240 mg IV every 2 weeks + BMS-986253 1200 mg IV every 2 weeks; Nivolumab 240 mg IV plus BMS-986253 1200mg IV every 2 weeks
Experimental: Nivolumab/Cabiralizumab combination	Drug: Nivolumab 240 mg IV every 2 weeks; Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy; Drug: Nivolumab 240 mg IV every 2 weeks + Cabiralizumab 4 mg/kg IV every 2 weeks; Nivolumab 240 mg IV plus Cabiralizumab 4 mg/kg IV every 2 weeks combination therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) of Cabiralizumab or BMS-986253 in combination with Nivolumab in comparison to Nivolumab monotherapy	6 Years

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Theodore Welling, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): September 12, 2019
• Primary Completion (Estimated): December 13, 2024
• Study Completion (Estimated): December 13, 2025

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: 18-01028

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No