Clinical trial NCT03656718: A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)
Official title: Phase I/II Pharmacokinetic Multi-Tumor Study of Subcutaneous Formulation of Nivolumab Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Neoplasms by Site
Keywords: Subcutaneous
Nivolumab
rHuPH20
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2018-09-04
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* Histologic or cytologic confirmation of advanced (metastatic and/or unresectable) solid tumors of one of the following tumor types:

  1. Metastatic squamous or non-squamous NSCLC
  2. RCC, advanced or metastatic
  3. Melanoma
  4. HCC
  5. CRC, metastatic (MSI-H or dMMR)
  6. In Part B, other solid tumor types may be considered at the discretion of the Medical Monitor
  7. In Part E, Metastatic urothelial carcinoma
* Measurable disease as per RECIST version 1.1 criteria
* ECOG performance status of 0 or 1

Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases
* Ocular melanoma
* Active, known, or suspected autoimmune disease

Other protocol defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Maximum Observed Serum Nivolumab Concentration (Cmax) - Parts A, B, D, and E
timeFrame: From first dose until approximately 21 days post first dose.
measure: Time Taken to Reach Cmax (Tmax) - Parts A, B, D, and E
timeFrame: From first dose until approximately 21 days post first dose.
measure: Area Under the Time-Serum Nivolumab Concentration Curve (AUC (TAU)) - Parts A, B, D, and E
timeFrame: From first dose until approximately 21 days post first dose.
measure: Observed Serum Nivolumab Concentration at the End of Dosing (Ctau) - Parts A, B, D, and E
timeFrame: At the end of dosing interval of Cycle 1 - first dose (Day 21 for Parts A, B and D; Day 15 for Part E)
measure: Lowest Observed Serum Nivolumab Concentration (Ctrough) During Part C - Part A and B Crossover Participants to Part C
timeFrame: 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)
Secondary outcomes:
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: From first dose until 100 days post last dose (up to approximately 28 months).
measure: Number of Participants Experiencing Treatment Related Adverse Events (TRAEs)
timeFrame: From first dose until 100 days post last dose (up to approximately 28 months).
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: From first dose until 100 days post last dose (up to approximately 28 months).
measure: Number of Participants Experiencing Treatment Related Serious Adverse Events (TRSAEs)
timeFrame: From first dose until 100 days post last dose (up to approximately 28 months).
measure: Number of Participants Experiencing Treatment Related Adverse Events (TRAEs) Leading to Discontinuation
timeFrame: From first dose until 100 days post last dose (up to approximately 28 months).
measure: Number of Participants Who Died
timeFrame: From randomization until data cutoff (up to approximately 46 months).
measure: Number of Participants With Select Laboratory Changes From Baseline
timeFrame: From first dose until 30 days post last dose (up to approximately 25 months).
measure: 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
timeFrame: From first dose until 2 days post last dose (up to approximately 24 months and 2 days).
measure: Number of Participants With Anti-Nivolumab Antibodies (ADAs) and Neutralizing Antibodies
timeFrame: At baseline and up to 100 days post last dose (up to approximately 28 months).
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute.
state: Georgia
city: Rockville
country: United States
facility: Local Institution - 0024
state: Maryland
city: Detroit
country: United States
facility: Local Institution - 0020
state: Michigan
city: Charlotte
country: United States
facility: Local Institution - 0001
state: North Carolina
city: Eugene
country: United States
facility: Local Institution - 0012
state: Oregon
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: Austin
country: United States
facility: Local Institution - 0010
state: Texas
city: Beaumont
country: United States
facility: Local Institution - 0009
state: Texas
city: Dallas
country: United States
facility: Local Institution - 0007
state: Texas
city: Tyler
country: United States
facility: Local Institution - 0011
state: Texas
city: Caba
country: Argentina
facility: Local Institution - 0035
city: Caba
country: Argentina
facility: Local Institution - 0025
city: Porto Alegre
country: Brazil
facility: Local Institution - 0038
state: RIO Grande DO SUL
city: Sao Paulo
country: Brazil
facility: Local Institution - 0037
city: Santiago
country: Chile
facility: Local Institution - 0005
city: Saint Herblain
country: France
facility: Local Institution - 0022
city: Villejuif
country: France
facility: Local Institution - 0021
city: Rozzano
country: Italy
facility: Local Institution - 0003
state: MI
city: Padova
country: Italy
facility: Local Institution - 0004
city: Mexico City
country: Mexico
facility: Local Institution - 0050
state: Distrito Federal
city: Mexico City
country: Mexico
facility: Local Institution - 0048
state: Distrito Federal
city: Monterrey
country: Mexico
facility: Local Institution - 0046
state: Nuevo León
city: Monterrey
country: Mexico
facility: Local Institution - 0047
state: Nuevo León
city: Puebla
country: Mexico
facility: Local Institution - 0049
city: Querétaro
country: Mexico
facility: Local Institution - 0045
city: Amsterdam
country: Netherlands
facility: Local Institution - 0026
state: Noord-Holland
city: Maastricht
country: Netherlands
facility: Local Institution - 0039
city: Rotorua
country: New Zealand
facility: Local Institution - 0040
state: Bay Of Plenty
city: Newtown
country: New Zealand
facility: Local Institution - 0018
state: Wellington
city: Dunedin
country: New Zealand
facility: Local Institution - 0014
city: Tauranga
country: New Zealand
facility: Local Institution - 0015
city: Warszawa
country: Poland
facility: Local Institution - 0019
state: Mazowieckie
city: Madrid
country: Spain
facility: Local Institution - 0017
city: Malaga
country: Spain
facility: Local Institution - 0016
city: Cardiff
country: United Kingdom
facility: Local Institution - 0033
state: Glamorgan
city: Liverpool
country: United Kingdom
facility: Local Institution - 0031
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: