Study of subcutaneous nivolumab monotherapy with or without Recombinant Human Hyaluronidase PH20 (rHuPH20)

2023-503554-12-00 Protocol CA209-8KX Phase I and Phase II (Integrated) - Other Ended

Start 9 Jan 2019 · End 13 Sep 2024 · Status Ended · 5 EU/EEA countries · 9 sites · Protocol CA209-8KX

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ended
Participants planned 220
Countries 5
Sites 9

lung cancer; kidney cancer; melanoma; liver cancer; colorectal cancer; bladder cancer

Parts A- D: To describe the pharmacokinetics of nivolumab administered subcutaneously, with or without rHuPH20 Part E: To evaluate the pharmacokinetics of SC nivolumab 600 mg Q2W coformulated with rHuPH20

Key facts

Sponsor
Bristol Myers Squibb International Corporation
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Trial duration
9 Jan 2019 → 13 Sep 2024
Decision date (initial)
2023-09-04
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
Bristol-Myers Squibb International Corporation

External identifiers

EU CT number
2023-503554-12-00
EudraCT number
2018-001585-42
WHO UTN
U1111-1212-4238
ClinicalTrials.gov
NCT03656718

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Therapy, Efficacy, Pharmacodynamic, Pharmacogenomic, Pharmacokinetic

Parts A- D: To describe the pharmacokinetics of nivolumab administered subcutaneously, with or without rHuPH20
Part E: To evaluate the pharmacokinetics of SC nivolumab 600 mg Q2W coformulated with rHuPH20

Secondary objectives 3

  1. To assess the safety profile of SC nivolumab
  2. To evaluate incidence of AEs in the broad scope MedDRA Anaphylactic Reaction SMQ and the select AE hypersensitivity/infusion reaction category
  3. To assess the immunogenicity of nivolumab

Conditions and MedDRA coding

lung cancer; kidney cancer; melanoma; liver cancer; colorectal cancer; bladder cancer

VersionLevelCodeTermSystem organ class
20.0 LLT 10064467 Urothelial carcinoma 10029104
21.0 PT 10061451 Colorectal cancer 100000004864
20.0 PT 10073071 Hepatocellular carcinoma 100000004864
20.0 LLT 10027481 Metastatic melanoma 10029104
21.1 PT 10061873 Non-small cell lung cancer 100000004864
21.1 PT 10067946 Renal cell carcinoma 100000004864

Regulatory references

Scientific advice from competent authorities
European Medicines Agency
Plan to share IPD
No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. - 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) Renal Cell Carcinoma, advanced or metastatic 3) Melanoma 4) Hepatocellular Carcinoma 5) Colorectal Cancer, metastatic (MSI-H or dMMR) 6) Urothelial carcinoma , metastatic(part E only)
  2. - Measurable disease as per RECIST version 1.1 criteria
  3. - ECOG performance status of 0 or 1

Exclusion criteria 3

  1. - Active brain metastases or leptomeningeal metastases
  2. - Ocular melanoma
  3. - Active, known, or suspected autoimmune disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

  1. Serum nivolumab Parts A, B, D, and E: -Cmax (Maximal concentration) -Tmax (Time to maximal concentration) -AUC(TAU)(Area under the concentration-time curve over the dosing interval) -Ctau (observed serum nivolumab concentration at the end of the dosing interval)
  2. Serum nivolumab Part C: -Ctrough (trough observed serum nivolumab concentration)

Secondary endpoints 4

  1. - Incidences of AEs, TRAEs, SAEs, TRSAEs, AEs/TRAEs leading to discontinuation, deaths, and laboratory abnormalities
  2. - Incidence of AEs in the MedDRA Anaphylactic Reaction broad scope SMQ occurring within 2 days after study drug administration
  3. - Incidence of events within the hypersensitivity/infusion reaction select AE category occurring within 2 days after any study drug administration.
  4. - Incidence of anti-nivolumab antibodies and neutralizing antibodies, if applicable

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

MDX1106 ONO-4538

PRD10108807 · Product

Active substance
Nivolumab
Other product name
40 mg/4 ml
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

MDX1106 ONO-4538

PRD260416 · Product

Active substance
Nivolumab
Other product name
100 mg/10 ml
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

OPDIVO 10 mg/mL concentrate for solution for infusion.

PRD2941375 · Product

Active substance
Nivolumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Authorisation status
Authorised
ATC code
L01FF01 — -
Marketing authorisation
EU/1/15/1014/002
MA holder
BRISTOL-MYERS SQUIBB PHARMA EEIG
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

OPDIVO 10 mg/mL concentrate for solution for infusion.

PRD2941372 · Product

Active substance
Nivolumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Authorisation status
Authorised
ATC code
L01FF01 — -
Marketing authorisation
EU/1/15/1014/001
MA holder
BRISTOL-MYERS SQUIBB PHARMA EEIG
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Nivolumab Subcutaneous

PRD10267386 · Product

Active substance
Nivolumab
Other product name
120 mg/ml
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

Nivolumab Subcutaneous

PRD10267387 · Product

Active substance
Nivolumab
Other product name
120mg/mL with rHuPH20
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol Myers Squibb International Corporation

26 Total trials 26 Ended
Commercial
Sponsor organisation
Bristol Myers Squibb International Corporation
Address
Terhulpsesteenweg 185
City
Watermaal-Bosvoorde
Postcode
1170
Country
Belgium

Scientific contact point

Organisation
Bristol Myers Squibb International Corporation
Contact name
GSM-CT

Public contact point

Organisation
Bristol Myers Squibb International Corporation
Contact name
GSM-CT

Third parties 9

OrganisationCity, countryDuties
Icon Laboratories Inc.
ORG-100037135
 Farmingdale, United States Other
Accenture Solutions Private Limited
ORG-100032592
 Chennai, India Data management
Azenta Germany GmbH
ORG-100039257
 Griesheim, Germany Other
Accenture Solutions Private Limited
ORG-100032592
 Bangaluru, India Other, Data management
Icon Laboratories Inc.
ORG-100037135
 Farmingdale, United States Other
Accenture Solutions Private Limited
ORG-100032592
 Chennai, India Other
Labcorp Central Laboratory Services LP
ORG-100032236
 Indianapolis, United States Other
Myriad RBM Inc.
ORG-100045698
 Austin, United States Other
Evidera Inc.
ORG-100028146
 Bethesda, United States Other

Locations

5 EU/EEA countries · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 12 2
Italy Ended 39 2
Netherlands Ended 10 2
Poland Ended 20 1
Spain Ended 15 2
Rest of world
United States, Chile, Brazil, United Kingdom, Argentina, New Zealand
 — 124 —

Investigational sites

France

2 sites · Ended
Institut Gustave Roussy
Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800, Villejuif
Centre Hospitalier Universitaire De Nantes
ICO – Site Rene Gauducheau, Boulevard Du Professeur Jacques Monod, 44800, Saint Herblain

Italy

2 sites · Ended
Humanitas Research Hospital
UO Oncologia Medica, Via Alessandro Manzoni 56, 20089, Rozzano
Istituto Oncologico Veneto
Oncologia Medica 1, Via Gattamelata 64, 35128, Padova

Netherlands

2 sites · Ended
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Oncology, Plesmanlaan 121, 1066 CX, Amsterdam
Maastricht University
Oncology, P Debyelaan 25, 6229 HX, Maastricht

Poland

1 site · Ended
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
Oddzial Badan Wczesnych Faz, Ul. Wilhelma Konrada Roentgena 5, 02-781, Warsaw

Spain

2 sites · Ended
Hospital Universitario Virgen De La Victoria
Oncology, Calle Del Arroyo Teatinos S N, 29010, Malaga
Hospital General Universitario Gregorio Maranon
ONCOLOGY, Calle Del Doctor Esquerdo 46, 28009, Madrid

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2019-04-02 2024-09-12 2019-07-03 2021-11-05
Italy 2019-03-01 2024-09-03 2019-03-12 2022-01-28
Netherlands 2019-05-07 2024-09-10 2019-07-02 2021-10-17
Poland 2019-01-09 2024-09-12 2019-02-07 2022-02-25
Spain 2019-06-03 2024-08-20 2019-06-03 2022-03-29

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

TitleSubmission dateStatusType
2023-503554-12-00_Final Summary of Results
SUM-96294
 2025-09-03T12:14:09 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
2023-503554-12-00_ Lay Person Summary of Results 2025-09-10T09:01:24 Submitted Laypersons Summary of Results
2023-503554-12-00_ Lay Person Summary of Results_Dutch version 2025-09-17T17:46:29 Submitted Laypersons Summary of Results
2023-503554-12-00_ Lay Person Summary of Results_Spanish version 2025-09-19T11:40:31 Submitted Laypersons Summary of Results
2023-503554-12-00_ Lay Person Summary of Results_Italian version 2025-09-23T17:57:49 Submitted Laypersons Summary of Results
2023-503554-12-00_Lay Person Summary of Results_Polish version 2025-09-24T14:42:39 Submitted Laypersons Summary of Results
2023-503554-12-00_ Lay Person Summary of Results_French version 2025-10-07T16:22:54 Submitted Laypersons Summary of Results

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-data-app-2-2-thru-app-7-6-redacted 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-safety-narratives-redacted 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-study-information-redacted_Part1 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-study-information-redacted_Part2 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-study-information-redacted_Part3 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-supplemental-figures-redacted 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-supplemental-tables-redacted 1
Clinical study report (for publication) 2023-503554-12-00 ca209-8kx-primary-csr-tp-synopsis-body-redacted 1
Laypersons summary of results (for publication) 2023-503554-12-00_ Lay Person Summary of Result_Italian version 1
Laypersons summary of results (for publication) 2023-503554-12-00_ Lay Person Summary of Results N/A
Laypersons summary of results (for publication) 2023-503554-12-00_ Lay Person Summary of Results N/A
Laypersons summary of results (for publication) 2023-503554-12-00_ Lay Person Summary of Results_FR 1
Laypersons summary of results (for publication) CA209-8KX-pls-Dutch-final 1
Laypersons summary of results (for publication) CA209-8KX-pls-eng-final_ES NA
Summary of results (for publication) 2023-503554-12-00_Final Summary of Results N/A

Application history

5 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-05-23 Netherlands Acceptable
2023-06-23
 2023-06-23
2 SUBSTANTIAL MODIFICATION SM-1 2023-10-20 Netherlands Acceptable
2023-12-01
 2023-12-04
3 NON SUBSTANTIAL MODIFICATION NSM-1 2023-12-07 Acceptable
2023-12-01
 2023-12-07
4 NON SUBSTANTIAL MODIFICATION NSM-2 2024-06-14 Netherlands Acceptable
2023-12-01
 2024-06-14
5 NON SUBSTANTIAL MODIFICATION NSM-3 2024-07-19 Netherlands Acceptable
2023-12-01
 2024-07-19

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