Hepatocellular Carcinoma
Conditions
Brief summary
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.
Interventions
DRUGNivolumab 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
DRUGNivolumab 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
DRUGNivolumab 240 mg IV every 2 weeks
Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy
Sponsors
NYU Langone Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Every 8 weeks for 1 year and every 3 months thereafter (assessed up to 5 years) | ORR is measured as the percentage of people in a study or treatment group who have a partial response or complete response to the treatment. ORR will be determined based upon RECIST v. 1.1 criteria. Per RECIST v. 1.1 criteria, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesions, compared to the baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | From treatment initiation until first sign of response (up to 5 years) | TTR is the amount of time it takes for a tumor to show a measurable decrease in size or other signs of response after treatment begins |
| Disease Control Rate (DOR) | Through study completion (assessed up to 5 years) | DOR is the percentage of patients who experience either a complete response (CR), a partial response (PR), or stable disease (SD) to a treatment |
| Progression Free Survival (PFS) | From date of treatment until the date of first documented progression (assessed up to 5 years) | PFS is measured as the time from the date of enrollment to disease progression per RECIST v. 1.1 criteria. |
| Overall Survival (OS) | From date of treatment until the date of death from any cause (assessed up to 5 years) | OS is the time from treatment start to death of participants. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab Monotherapy Nivolumab 240 mg IV every 2 weeks: Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy | 6 |
| Nivolumab/BMS-986253 Combination 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
Nivolumab 240 mg IV every 2 weeks: Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy | 7 |
| Nivolumab/Cabiralizumab Combination 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
Nivolumab 240 mg IV every 2 weeks: Arm 1 (control) Nivolumab 240mg IV every 2 weeks monotherapy | 0 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Nivolumab Monotherapy | Total | Nivolumab/BMS-986253 Combination |
|---|---|---|---|
| Age, Continuous | 72.5 years | 70 years | 70 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 11 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 7 Participants | 4 Participants |
| Region of Enrollment United States | 6 participants | 13 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 2 / 7 | 0 / 0 |
| other Total, other adverse events | 5 / 6 | 7 / 7 | 0 / 0 |
| serious Total, serious adverse events | 1 / 6 | 3 / 7 | 0 / 0 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is measured as the percentage of people in a study or treatment group who have a partial response or complete response to the treatment. ORR will be determined based upon RECIST v. 1.1 criteria. Per RECIST v. 1.1 criteria, a Complete Response (CR) is the disappearance of all target lesions, and a Partial Response (PR) is at least a 30% decrease in the sum of the longest diameters (LD) of the target lesions, compared to the baseline.
Time frame: Every 8 weeks for 1 year and every 3 months thereafter (assessed up to 5 years)
Population: 1 subject on the monotherapy arm withdrew consent after randomization, prior to starting treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab Monotherapy | Objective Response Rate (ORR) | 20 percentage of particpants |
| Nivolumab/BMS-986253 Combination | Objective Response Rate (ORR) | 28.57 percentage of particpants |
Secondary
Disease Control Rate (DOR)
DOR is the percentage of patients who experience either a complete response (CR), a partial response (PR), or stable disease (SD) to a treatment
Time frame: Through study completion (assessed up to 5 years)
Population: 1 subject on the monotherapy arm withdrew consent after randomization, prior to starting treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab Monotherapy | Disease Control Rate (DOR) | 80 percentage of participants |
| Nivolumab/BMS-986253 Combination | Disease Control Rate (DOR) | 57.14 percentage of participants |
Secondary
Overall Survival (OS)
OS is the time from treatment start to death of participants.
Time frame: From date of treatment until the date of death from any cause (assessed up to 5 years)
Population: 1 subject on the monotherapy arm withdrew consent after randomization, prior to starting treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Overall Survival (OS) | 465 days |
| Nivolumab/BMS-986253 Combination | Overall Survival (OS) | 409 days |
Secondary
Progression Free Survival (PFS)
PFS is measured as the time from the date of enrollment to disease progression per RECIST v. 1.1 criteria.
Time frame: From date of treatment until the date of first documented progression (assessed up to 5 years)
Population: 1 subject on the monotherapy arm withdrew consent after randomization, prior to starting treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Progression Free Survival (PFS) | 191 days |
| Nivolumab/BMS-986253 Combination | Progression Free Survival (PFS) | 171 days |
Secondary
Time to Response (TTR)
TTR is the amount of time it takes for a tumor to show a measurable decrease in size or other signs of response after treatment begins
Time frame: From treatment initiation until first sign of response (up to 5 years)
Population: Number of subjects who showed response in each arm were included in analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab Monotherapy | Time to Response (TTR) | 126 days |
| Nivolumab/BMS-986253 Combination | Time to Response (TTR) | 116 days |