A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)
- Registration Number
- NCT03656718
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to investigate the effects of nivolumab when given under the skin with or without rHuPH20.
This study will include participants with 1 of the following advanced or metastatic tumors approved for treatment with nivolumab monotherapy:
* non-small cell lung cancer (NSCLC)
* renal cell carcinoma (RCC)
* unresectable or metastatic melanoma
* hepatocellular carcinoma (HCC)
* microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC)
* in Part B, other solid tumors may be considered at the discretion of the Clinical Trial Physician
* In addition to the above tumors, Part E will also include participants with metastatic urothelial carcinoma (mUC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 139
-
Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types:
- Metastatic squamous or non-squamous NSCLC
- RCC, advanced or metastatic
- Melanoma
- HCC
- CRC, metastatic (MSI-H or dMMR)
- In Part B, other solid tumor types may be considered at the discretion of the Medical Monitor
- In Part E, Metastatic urothelial carcinoma
-
Measurable disease as per RECIST version 1.1 criteria
-
ECOG performance status of 0 or 1
- Active brain metastases or leptomeningeal metastases
- Ocular melanoma
- Active, known, or suspected autoimmune disease
Other protocol defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C: nivolumab (dose 3) + rHuPH20 nivolumab - Part B, Group 3: nivolumab (dose 2) + rHuPH20 rHuPH20 - Part D, Group 5: nivolumab (dose 3) + rHuPH20 rHuPH20 - Part A, Group 1: nivolumab (dose 1) + rHuPH20 nivolumab - Part A, Group 1: nivolumab (dose 1) + rHuPH20 rHuPH20 - Part C: nivolumab (dose 3) + rHuPH20 rHuPH20 - Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20 rHuPH20 - Part D, Group 5: nivolumab (dose 3) + rHuPH20 nivolumab - Part B, Group 3: nivolumab (dose 2) + rHuPH20 nivolumab - Part B, Group 2: nivolumab (dose 1) nivolumab - Part B, Group 4: nivolumab (dose 2) nivolumab - Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20 nivolumab -
- Primary Outcome Measures
Name Time Method Maximum Observed Serum Nivolumab Concentration (Cmax) - Parts A, B, D, and E From first dose until approximately 21 days post first dose. Cmax is the maximum observed serum nivolumab concentration. Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Time Taken to Reach Cmax (Tmax) - Parts A, B, D, and E From first dose until approximately 21 days post first dose. Tmax is the time taken to reach the maximum observed serum nivolumab concentration (Cmax). Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Area Under the Time-Serum Nivolumab Concentration Curve (AUC (TAU)) - Parts A, B, D, and E From first dose until approximately 21 days post first dose. AUC (TAU) is the area measured under the concentration-time curve taken over the dosing interval. Collected for Arm A, B, and D on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 21. Collected for Arm E on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 4, Cycle 1 Day 8, Cycle 1 Day 15.
Observed Serum Nivolumab Concentration at the End of Dosing (Ctau) - Parts A, B, D, and E At the end of dosing interval of Cycle 1 - first dose (Day 21 for Parts A, B and D; Day 15 for Part E) Ctau is the observed serum nivolumab concentration at the end of the dosing interval. Collected for Arma A, B, and D.
Lowest Observed Serum Nivolumab Concentration (Ctrough) During Part C - Part A and B Crossover Participants to Part C On Day 1 of Cycles 2, 3, 5, 9, 13, and 19 of Part C (Day 1 of Part C: up to 14 months from Baseline; each cycle was 28 days) Ctrough assessed during Part C. Ctrough is the lowest observed serum nivolumab concentration.
- Secondary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events (AEs) From first dose until 100 days post last dose (up to approximately 28 months). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of Participants Experiencing Treatment Related Adverse Events (TRAEs) From first dose until 100 days post last dose (up to approximately 28 months). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. TRAEs are AEs where a reasonable causal relationship exists between study treatment administration and the AE.
Number of Participants Experiencing Serious Adverse Events (SAEs) From first dose until 100 days post last dose (up to approximately 28 months). A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: (a) results in death, (b) is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), and/ or (c) requires inpatient hospitalization or causes prolongation of existing hospitalization.
Number of Participants Experiencing Treatment Related Serious Adverse Events (TRSAEs) From first dose until 100 days post last dose (up to approximately 28 months). A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: (a) results in death, (b) is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), and/ or (c) requires inpatient hospitalization or causes prolongation of existing hospitalization. TRSAEs are SAEs where a reasonable causal relationship exists between study treatment administration and the SAE.
Number of Participants Experiencing Treatment Related Adverse Events (TRAEs) Leading to Discontinuation From first dose until 100 days post last dose (up to approximately 28 months). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. TRAEs are AEs where a reasonable causal relationship exists between study treatment administration and the AE.
Number of Participants Who Died From randomization until data cutoff (up to approximately 46 months). Number of participants who died due to any cause.
Number of Participants With Select Laboratory Changes From Baseline From first dose until 30 days post last dose (up to approximately 25 months). Laboratory parameters including hematology, chemistry, liver function, and renal function summarized using worst grade NCI CTCAE v.5 criteria. Baseline refers to evaluations with a date on or prior to the day of first dose of study treatment.
Number of Participants Experiencing Any Select Adverse Events Within the Hypersensitivity/Infusion Reaction Category and Broad Standardized MedDRA Query (SMQ) of Anaphylactic Reaction Occurring Within 2 Days of Study Drug Administration From first dose until 2 days post last dose (up to approximately 24 months and 2 days). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of Participants With Anti-Nivolumab Antibodies (ADAs) and Neutralizing Antibodies At baseline and up to 100 days post last dose (up to approximately 28 months). Anti-drug antibody (ADA) Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (\>=) than baseline positive titer) at any time after initiation of treatment; Neutralizing Positive: At least one ADA-positive sample with neutralizing antibodies detected post-baseline.
Baseline ADA Positive: A participant with a baseline ADA-positive sample. Baseline refers to evaluations with a date on or prior to the day of first dose of study treatment.
Trial Locations
- Locations (36)
Local Institution - 0012
🇺🇸Eugene, Oregon, United States
Greenville Health System
🇺🇸Greenville, South Carolina, United States
Local Institution - 0011
🇺🇸Tyler, Texas, United States
Local Institution - 0035
🇦🇷Caba, Argentina
Local Institution - 0025
🇦🇷Caba, Argentina
Local Institution - 0010
🇺🇸Austin, Texas, United States
Local Institution - 0009
🇺🇸Beaumont, Texas, United States
Local Institution - 0007
🇺🇸Dallas, Texas, United States
Local Institution - 0038
🇧🇷Porto Alegre, RIO Grande DO SUL, Brazil
Local Institution - 0037
🇧🇷Sao Paulo, Brazil
Local Institution - 0005
🇨🇱Santiago, Chile
Local Institution - 0022
🇫🇷Saint Herblain, France
Local Institution - 0048
🇲🇽Mexico City, Distrito Federal, Mexico
Local Institution - 0046
🇲🇽Monterrey, Nuevo León, Mexico
Local Institution - 0021
🇫🇷Villejuif, France
Local Institution - 0003
🇮🇹Rozzano, MI, Italy
Local Institution - 0004
🇮🇹Padova, Italy
Local Institution - 0050
🇲🇽Mexico City, Distrito Federal, Mexico
Local Institution - 0047
🇲🇽Monterrey, Nuevo León, Mexico
Local Institution - 0049
🇲🇽Puebla, Mexico
Local Institution - 0018
🇳🇿Newtown, Wellington, New Zealand
Local Institution - 0014
🇳🇿Dunedin, New Zealand
Local Institution - 0045
🇲🇽Querétaro, Mexico
Local Institution - 0026
🇳🇱Amsterdam, Noord-Holland, Netherlands
Local Institution - 0039
🇳🇱Maastricht, Netherlands
Local Institution - 0040
🇳🇿Rotorua, Bay Of Plenty, New Zealand
Local Institution - 0015
🇳🇿Tauranga, New Zealand
Local Institution - 0019
🇵🇱Warszawa, Mazowieckie, Poland
Local Institution - 0016
🇪🇸Malaga, Spain
Local Institution - 0033
🇬🇧Cardiff, Glamorgan, United Kingdom
Local Institution - 0031
🇬🇧Liverpool, United Kingdom
Local Institution - 0017
🇪🇸Madrid, Spain
Winship Cancer Institute.
🇺🇸Atlanta, Georgia, United States
Local Institution - 0020
🇺🇸Detroit, Michigan, United States
Local Institution - 0001
🇺🇸Charlotte, North Carolina, United States
Local Institution - 0024
🇺🇸Rockville, Maryland, United States