A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)

NCT03656718 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CA209-8KX2018-001585-42
• Study Type: interventional
• Target: 139
• Locations: 12 countries
• Sites: 36

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).

Conditions

Neoplasms by Site

Keywords

Subcutaneous; Nivolumab; rHuPH20

Outcome Measures

Primary Outcomes (5)

• Maximum Observed Serum Nivolumab Concentration (Cmax) - Parts A, B, D, and E

  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.

  From first dose until approximately 21 days post first dose.

• Time Taken to Reach Cmax (Tmax) - Parts A, B, D, and E

  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.

  From first dose until approximately 21 days post first dose.

• Area Under the Time-Serum Nivolumab Concentration Curve (AUC (TAU)) - Parts A, B, D, and E

  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.

  From first dose until approximately 21 days post first dose.

• Observed Serum Nivolumab Concentration at the End of Dosing (Ctau) - Parts A, B, D, and E

  Ctau is the observed serum nivolumab concentration at the end of the dosing interval. Collected for Arma A, B, and D.

  At the end of dosing interval of Cycle 1 - first dose (Day 21 for Parts A, B and D; Day 15 for Part E)

• Lowest Observed Serum Nivolumab Concentration (Ctrough) During Part C - Part A and B Crossover Participants to Part C

  Ctrough assessed during Part C. Ctrough is the lowest observed serum nivolumab concentration.

  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 (9)

• Number of Participants Experiencing Adverse Events (AEs)

  From first dose until 100 days post last dose (up to approximately 70 months).

• Number of Participants Experiencing Treatment Related Adverse Events (TRAEs)

  From first dose until 100 days post last dose (up to approximately 70 months).

• Number of Participants Experiencing Serious Adverse Events (SAEs)

  From first dose until 100 days post last dose (up to approximately 70 months).

• Number of Participants Experiencing Treatment Related Serious Adverse Events (TRSAEs)

  From first dose until 100 days post last dose (up to approximately 70 months).

• Number of Participants Experiencing Treatment Related Adverse Events (TRAEs) Leading to Discontinuation

  From first dose until 100 days post last dose (up to approximately 70 months).

Study Arms (7)

Part A, Group 1: nivolumab (dose 1) + rHuPH20

EXPERIMENTAL

Biological: nivolumab; Drug: rHuPH20

Part B, Group 3: nivolumab (dose 2) + rHuPH20

EXPERIMENTAL

Biological: nivolumab; Drug: rHuPH20

Part B, Group 2: nivolumab (dose 1)

EXPERIMENTAL

Biological: nivolumab

Part B, Group 4: nivolumab (dose 2)

EXPERIMENTAL

Biological: nivolumab

Part C: nivolumab (dose 3) + rHuPH20

EXPERIMENTAL

Biological: nivolumab; Drug: rHuPH20

Part D, Group 5: nivolumab (dose 3) + rHuPH20

EXPERIMENTAL

Biological: nivolumab; Drug: rHuPH20

Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20

EXPERIMENTAL

Biological: nivolumab; Drug: rHuPH20

Interventions

nivolumab BIOLOGICAL

(Subcutaneous) Specified dose on specified days

Also known as: Opdivo, BMS-986298

Part A, Group 1: nivolumab (dose 1) + rHuPH20; Part B, Group 2: nivolumab (dose 1); Part B, Group 3: nivolumab (dose 2) + rHuPH20; Part B, Group 4: nivolumab (dose 2); Part C: nivolumab (dose 3) + rHuPH20; Part D, Group 5: nivolumab (dose 3) + rHuPH20; Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20

rHuPH20 DRUG

Specified dose on specified days Permeation enhancer

Also known as: ENHANZE™ DP

Part A, Group 1: nivolumab (dose 1) + rHuPH20; Part B, Group 3: nivolumab (dose 2) + rHuPH20; Part C: nivolumab (dose 3) + rHuPH20; Part D, Group 5: nivolumab (dose 3) + rHuPH20; Part E, Group 6: nivolumab (dose 4) coformulated with rHuPH20

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (36)

Winship Cancer Institute.

Atlanta, Georgia, 30322, United States

Location

Local Institution - 0024

Rockville, Maryland, 20850, United States

Location

Local Institution - 0020

Detroit, Michigan, 48201-2014, United States

Location

Local Institution - 0001

Charlotte, North Carolina, 28204, United States

Location

Local Institution - 0012

Eugene, Oregon, 97401, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Local Institution - 0010

Austin, Texas, 78705, United States

Location

Local Institution - 0009

Beaumont, Texas, 77702-1449, United States

Location

Local Institution - 0007

Dallas, Texas, 75246, United States

Location

Local Institution - 0011

Tyler, Texas, 75702, United States

Location

Local Institution - 0035

CABA, 1199, Argentina

Location

Local Institution - 0025

CABA, 1426, Argentina

Location

Local Institution - 0038

Porto Alegre, Rio Grande do Sul, 90610000, Brazil

Location

Local Institution - 0037

São Paulo, 05651-901, Brazil

Location

Local Institution - 0005

Santiago, 0, Chile

Location

Local Institution - 0022

Saint-Herblain, 44805, France

Location

Local Institution - 0021

Villejuif, 94805, France

Location

Local Institution - 0003

Rozzano, MI, 20089, Italy

Location

Local Institution - 0004

Padua, 35128, Italy

Location

Local Institution - 0050

Mexico City, Mexico City, 03100, Mexico

Location

Local Institution - 0048

Mexico City, Mexico City, 14080, Mexico

Location

Local Institution - 0046

Monterrey, Nuevo León, 64710, Mexico

Location

Local Institution - 0047

Monterrey, Nuevo León, 66460, Mexico

Location

Local Institution - 0049

Puebla City, 72424, Mexico

Location

Local Institution - 0045

Querétaro, 76000, Mexico

Location

Local Institution - 0026

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Local Institution - 0039

Maastricht, 6229 HX, Netherlands

Location

Local Institution - 0040

Rotorua, Bay of Plenty, 3046, New Zealand

Location

Local Institution - 0018

Newtown, Wellington Region, 6021, New Zealand

Location

Local Institution - 0014

Dunedin, 9012, New Zealand

Location

Local Institution - 0015

Tauranga, 3112, New Zealand

Location

Local Institution - 0019

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Local Institution - 0017

Madrid, 28007, Spain

Location

Local Institution - 0016

Málaga, 29010, Spain

Location

Local Institution - 0033

Cardiff, Glamorgan, CF14 2TL, United Kingdom

Location

Local Institution - 0031

Liverpool, L7 8YA, United Kingdom

Location

Related Publications (1)

• Lonardi S, Lugowska I, O'Donnell A, Jackson C, Latten-Jansen LM, North R, Bahleda R, Garrido M, Santoro A, Chacon MR, Li L, Joseph D, Vezina HE, Aras U, Bennett B, Perumal D, Gurm B, Ng WT, Harvey RD, Trigo J, Calvo A. Pharmacokinetics and safety of subcutaneous nivolumab: results from the phase I/II CheckMate 8KX study. J Immunother Cancer. 2025 Oct 5;13(10):e011918. doi: 10.1136/jitc-2025-011918.

  PMID: 41052885 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Neoplasms by Site

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2018
• First Posted: September 4, 2018
• Study Start: October 29, 2018
• Primary Completion: September 7, 2022
• Study Completion: September 12, 2024
• Last Updated: November 12, 2025
• Results First Posted: February 20, 2025

Record last verified: 2025-10

Locations

NZ (4); BR (2); PL (1); FR (2); ES (2); GB (2); AR (2); US (10); CL (1); IT (2); ME (6); NL (2)