A Phase 3 Study of Nivolumab versus Placebo for Participants with Hepatocellular Cancer Who Are at High Risk of Recurrence after Hepatic Resection or Ablation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bristol-Myers Squibb Services Unlimited Company

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2018 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-508726-10-00

EudraCT number

2017-002755-29

WHO UTN

U1111-1198-6193

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To compare recurrence-free survival (RFS) (based on BICR assessment) of nivolumab vs placebo in all randomized participants.

Secondary objectives 2

1. To compare overall survival (OS) of nivolumab vs placebo in all randomized participants.
2. To evaluate time to recurrence (TTR) (based on BICR assessment) of nivolumab vs placebo in all randomized participants.

Conditions and MedDRA coding

Hepatocellular Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Males and females, ages 18 or older.
2. Participants must have a first diagnosis of HCC amenable for management with curative intent by resection or local ablation.
3. Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC.
4. Participants are eligible to enroll if they have undergone: i) Hepatic resection and have the following tumor characteristics: up to three tumors, at least one with a diameter > 5 cm OR none with a diameter > 5 cm but with confirmation of microvascular invasion or poorly /undifferentiated HCC; or more than three tumors, none with a diameter > 5 cm ii) Local ablation [radiofrequency ablation (RFA) or microwave ablation (MWA)] and have the following tumor characteristics: solitary tumor > 3cm but <=5 cm; OR Multiple tumors (up to 4), none with a diameter > 5 cm
5. Participants must have complete resection response, or must have achieved radiologically documented complete resection after local ablation.
6. All participants are required to have imaging studies confirming disease-free status at least 4 weeks after either complete tumor removal after surgical resection or local ablation, and within 4 weeks prior to randomization.
7. Child-Pugh Score 5 or 6.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.

Exclusion criteria 13

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
2. Prior recurrence of HCC.
3. Any evidence of tumor metastasis or co-existing malignant disease.
4. Participants showing evidence of macrovascular invasion on imaging tests.
5. Participants who have undergone a liver transplant or those who are in the waiting list for liver transplantation.
6. Active co-infection with both Hepatitis B and C, OR Hepatitis D and B.
7. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
8. Participants with an active, known or suspected autoimmune disease.
9. Participants with a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment.
10. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured.
11. Participants previously receiving any prior therapy for HCC, including loco-regional therapies, before or after resection or ablation.
12. Participants receiving or expected to receive IFN-based therapies during the study period.
13. Positive pregnancy test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Recurrence free survival (RFS), defined as the time from randomization to the first documented disease recurrence or death (by any cause), whichever occurs first.

Secondary endpoints 2

1. OS, defined as the time between the date of randomization and the date of death (by any cause).
2. Time to Recurrence (TTR), defined as the time from randomization to the first documented disease recurrence.

Investigational products

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

Test 1

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bristol-Myers Squibb Services Unlimited Company

Sponsor organisation

Bristol-Myers Squibb Services Unlimited Company

Address

Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2

City

Dublin 15

Postcode

D15 T867

Country

Ireland

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 10

Locations

8 EU/EEA countries · 42 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 70 files

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

Application history

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