Phase 1/2 study of Nivolumab and Relatlimab in Combination with Bevacizumab in First-line HCC

Overview

Sponsor-declared trial summary

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

2 Sep 2022 → 18 Nov 2025

Decision date (initial)

2024-04-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-510649-33-00

EudraCT number

2021-003606-53

WHO UTN

U1111-1267-1579

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Efficacy, Safety, Dose response, Pharmacokinetic

1. To determine the RP2D (recommended Phase 2 dose) of relatlimab, nivolumab, and bevacizumab triplet combination in participants with advanced/metastatic HCC (hepatocellular carcinoma) who have not received prior systemic therapy.
2. To evaluate ORR (objective response rate) of the relatlimab, nivolumab, and bevacizumab triplet combination relative to nivolumab and bevacizumab doublet combination in all randomized participants
with advanced/metastatic HCC who have not received prior systemic therapy.

Secondary objectives 2

1. To estimate key efficacy endpoints of the relatlimab, nivolumab, and bevacizumab triplet combination and the nivolumab and bevacizumab in doublet combination in all randomized participants with advanced/metastatic HCC who have not received prior systemic therapy and all randomized participants who express LAG-3 (lymphocyte activation gene-3) (≥ 1%) by immunohistochemistry (IHC).
2. To determine the safety and tolerability of the relatlimab, nivolumab, and bevacizumab triplet combination in all treated participants with advanced/metastatic HCC who have not received prior systemic therapy

Conditions and MedDRA coding

Advanced/metastatic hepatocellular carcinoma (HCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 18 years of age
2. Previously untreated for advanced/metastatic HCC
3. ECOG 0-1
4. Child-Pugh A
5. Barcelona Clinical Liver Cancer stage B or C
6. For detailed inclusion criteria, please refer to clinical protocol.

Exclusion criteria 5

1. Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2. Prior disease history with increased risk of bleeding
3. Clinically significant ascites
4. Use of anticoagulant therapies
5. For detailed exclusion criteria, please refer to clinical protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: Will be assessed by analyzing the rate of dose-limiting toxicities (unwanted side effects) among patients treated at various dose levels; once safety is confirmed, Part 2 will begin.
2. Part 2: Efficacy will be evaluated by comparing the objective response rate (proportion of participants who respond to treatment) of each treatment, in participants with metastatic disease as well as in participants whose disease is limited to their liver.

Secondary endpoints 2

1. Additional efficacy endpoints will be tested in both groups of participants, including evaluating progression-free survival (time from start of treatment until worsening of disease).
2. Safety will be evaluated in both groups of participants, specifically reviewing adverse events (unwanted side effects), serious adverse events, and immune-mediated adverse events (unwanted side-effects caused by an overactive immune system) from first dose to 30 or 135 days after the last dose.

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol Myers Squibb International Corporation

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

Head of the GSM-CT

Public contact point

Organisation

Bristol Myers Squibb International Corporation

Contact name

Head of the GSM-CT

Third parties 15

Locations

5 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 56 files

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

Application history

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