An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread

2023-508207-21-00 Protocol CA224-048 Phase I and Phase II (Integrated) - Other Ended

Start 8 Feb 2019 · End 20 Feb 2025 · Status Ended · 3 EU/EEA countries · 9 sites · Protocol CA224-048

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ended
Participants planned 325
Countries 3
Sites 9

Advanced Malignant Tumors

- Part 1A and Part 1B: To determine the safety, tolerability, DLTs, and MTD of relatlimab administered in combination with nivolumab and BMS-986205 or nivolumab and ipilimumab in participants with advanced malignant tumors. - Part 2A and Part 2B: To investigate safety and tolerability of relatlimab triple combinations …

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
8 Feb 2019 → 20 Feb 2025
Decision date (initial)
2024-04-03
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
2023-508207-21-00
EudraCT number
2018-000058-22
WHO UTN
U1111-1207-2938
ClinicalTrials.gov
NCT03459222

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Dose response, Efficacy, Pharmacogenomic, Pharmacodynamic

- Part 1A and Part 1B: To determine the safety, tolerability, DLTs, and
MTD of relatlimab administered in combination
with nivolumab and BMS-986205 or nivolumab and ipilimumab in
participants with advanced malignant tumors.
- Part 2A and Part 2B: To investigate safety and tolerability of relatlimab
triple combinations in distinct cohorts of participants with advanced
malignant tumors.
- To investigate the antitumor activity of relatlimab triple combinations
in participants with advanced malignant tumors.

Secondary objectives 1

  1. To investigate the antitumor activity of relatlimab triple combinations in participants with advanced malignant tumors.

Conditions and MedDRA coding

Advanced Malignant Tumors

VersionLevelCodeTermSystem organ class
21.0 LLT 10048683 Advanced cancer 10029104

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. - Histologic or cytologic confirmation of an incurable solid malignancy that is advanced (metastatic and/or unresectable), with measurable disease per RECIST v1.1
  2. -Available tumor tissue for biomarker analysis
  3. - Eastern Cooperative Oncology Group Performance Status (ECOG) status of 0 or 1

Exclusion criteria 3

  1. - Participants with known or suspected uncontrolled CNS metastases or with the CNS as the only site of active disease
  2. - Participants with a history of interstitial lung disease (ILD) /pneumonitis
  3. - Concurrent malignancy (present during screening) requiring treatment or history of prior malignancy active within 2 years prior to treatment assignment (ie, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before treatment assignment and the participant has no evidence of disease). Participants with history of prior early stage basal/squamous cell skin cancer or noninvasive or in situ cancers that have undergone definitive treatment at any time are also eligible

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

  1. Number of clinical laboratory test abnormalities
  2. Number of Adverse Events (AEs)
  3. Number of Serious Adverse Events (SAEs)
  4. Number of AEs meeting protocol defined dose-limiting toxicity (DLT) criteria
  5. Number of AEs leading to discontinuation and deaths
  6. Objective Response Rate (ORR)
  7. Disease Control Rate (DCR)
  8. Median Duration of Response (mDOR)

Secondary endpoints 1

  1. Progression Free Survival (PFS)

Investigational products

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

Test 7

linrodostat mesylate; IDO1 inhibitor

PRD11037226 · Product

Active substance
Linrodostat Mesilate
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

linrodostat mesylate; IDO1 inhibitor

PRD11037227 · Product

Active substance
Linrodostat Mesilate
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

linrodostat mesylate; IDO1 inhibitor

PRD11037230 · Product

Active substance
Linrodostat Mesilate
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

Relatlimab intravenous

PRD9859719 · Product

Active substance
Relatlimab
Substance synonyms
BMS986016, BMS-986016
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

Ipilimumab

PRD191357 · Product

Active substance
Ipilimumab
Substance synonyms
BMS734016, HLX13, IBI310
Other product name
MDX-010
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
Authorisation status
Not Authorised
MA holder
BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
Paediatric formulation
No
Orphan designation
No

Ipilimumab

PRD191358 · Product

Active substance
Ipilimumab
Substance synonyms
BMS734016, HLX13, IBI310
Other product name
MDX-010
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS USE
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 11

OrganisationCity, countryDuties
Myriad RBM Inc.
ORG-100045698
 Austin, United States Other
Labcorp Central Laboratory Services SARL
ORG-100011524
 Meyrin, Switzerland Other
Icon Laboratory Services Inc.
ORG-100037135
 Farmingdale, United States Other
Accenture Services Pvt. Ltd.
ORL-000000127
 Bengaluru, India Other, Data management
Azenta US Inc.
ORG-100012907
 Indianapolis, United States Other
Q2 Solutions
ORL-000000131
 Livingston, United Kingdom Other
Pathai Inc.
ORG-100031209
 Boston, United States Other
PPD Development LP
ORG-100011560
 Richmond, United States Other
Accenture Services Pvt. Ltd.
ORL-000000126
 Bengaluru, India Other, Data management
Biotel Research LLC
ORG-100039864
 Rochester, United States Other
Mosaic Laboratories LLC
ORG-100042385
 Lake Forest, United States Other

Locations

3 EU/EEA countries · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 54 3
Italy Ended 41 2
Spain Ended 35 4
Rest of world
Australia, Switzerland, United Kingdom
 — 195 —

Investigational sites

France

3 sites · Ended
Institut Gustave Roussy
Oncology, 114 Rue Edouard Vaillant, 94800, Villejuif
Assistance Publique Hopitaux De Marseille
Oncology, 264 Rue Saint Pierre, 13005, Marseille
Centre Hospitalier Universitaire De Toulouse
Oncology, 1 Avenue Irene Joliot Curie, 31059, Toulouse Cedex 9

Italy

2 sites · Ended
IRCCS Istituto Nazionale Tumori Fondazione Pascale
S.C. melanoma, immunoterapia oncologica e terapie innovative, Via Mariano Semmola 52, 80131, Naples
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Oncologia Medica, Via Piero Maroncelli 40, 47014, Meldola

Spain

4 sites · Ended
Hospital Universitario Regional De Malaga
Oncologia, Avenida De Carlos De Haya Sn, 29010, Malaga
Hospital Universitario 12 De Octubre
Oncologia, Bloque D, Avenida De Cordoba Sn, Madrid
Clinica Universidad De Navarra
Oncologia, Avenue Pio XII 36, 31008, Pamplona
Hospital Universitario Hm Sanchinarro
Oncologia, Calle Ona 10, 28050, 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 2019-06-17 2024-08-02 2019-06-26 2021-11-26
Italy 2019-02-08 2025-02-14 2019-02-25 2022-08-19
Spain 2019-03-28 2025-02-19 2019-09-27 2022-09-02

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
2023-508207-21-00_Final Summary of Results
SUM-117071
 2026-01-29T17:53:05 Submitted Summary of Results

Layperson summary Annex V

TitleSubmission dateStatusType
2023-508207-21-00_Lay Person Summary of Results 2026-02-12T15:21:43 Submitted Laypersons Summary of Results
2023-508207-21-00_Lay Person Summary of Results_IT 2026-03-20T14:57:40 Submitted Laypersons Summary of Results

Documents 10 files

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

TypeTitleVersion
Laypersons summary of results (for publication) 2023-508207-21-00_Lay Person Summary of Results N/A
Laypersons summary of results (for publication) 2023-508207-21-00_Lay Person Summary of Results_IT 1
Protocol (for publication) D1_Protocol Admin Letter_04_2023-508207-21-00_ redacted 04
Protocol (for publication) D1_Protocol Admin Letter_05_2023-508207-21-00_redacted 05
Protocol (for publication) D1_Protocol_2023-508207-21-00_Redacted PA07
Summary of results (for publication) 2023-508207-21-00_Final Summary of Results N/A
Synopsis of the protocol (for publication) D1_Protocol Synopsis_2023-508207-21-00_ EN 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_2023-508207-21-00_ ES 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_2023-508207-21-00_FR 1
Synopsis of the protocol (for publication) D1_Protocol Synopsis_2023-508207-21-00_IT 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-02-05 Italy Acceptable
2024-03-19
 2024-03-19
2 SUBSTANTIAL MODIFICATION SM-1 2024-07-15 Italy Acceptable
2024-08-30
 2024-08-30
3 SUBSTANTIAL MODIFICATION SM-2 2024-10-11 Italy Acceptable
2024-12-02
 2024-12-02
4 NON SUBSTANTIAL MODIFICATION NSM-2 2025-02-04 Italy Acceptable
2024-12-02
 2025-02-04

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