Regorafenib-pembrolizumab vs. TACE/TARE in intermediate-stage HCC beyond up-to-7.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Translational Research In Oncology

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Mar 2024 → 26 Feb 2026

Decision date (initial)

2023-11-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Bayer HealthCare Pharmaceuticals Inc., 100 Bayer Boulevard, PO Box 915, Whippany, NJ 07981-0915, USA

External identifiers

EU CT number

2022-501969-42-00

ClinicalTrials.gov

NCT04777851

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Compare PFS for Rego-Pembro versus TACE/TARE in patients with intermediate-stage HCC, based on Investigator´s assessment (using mRECIST for HCC).

Secondary objectives 7

1. Compare PFS for Rego-Pembro versus TACE/TARE in patients with intermediate-stage HCC, based on Investigator´s assessment (using RECIST 1.1).
2. Compare PFS for Rego-Pembo versus TACE/TARE in patients with intermediate-stage HCC, based on BICR assessment.
3. Compare OS for Rego-Pembro versus TACE/TARE in patients with intermediate-stage HCC.
4. Evaluate the two treatment arms with respect to ORR.
5. Evaluate the two treatment arms with respect to time to unTACEable progression (TTUP).
6. Evaluate the two treatment arms with respect to duration of response (DOR).
7. Secondary Safety Objectives: Evaluate safety and tolerability of the trial treatments.

Conditions and MedDRA coding

Intermediate-stage hepatocellular carcinoma with beyond up-to-7 criteria.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Signed and dated Patient Informed Consent Form (PICF).
2. ≥ 18 years-old at the time of PICF signature.
3. Confirmed diagnosis of HCC.
4. Intermediate-stage HCC, defined as follows: 1. Multinodular HCC localized to the liver, 2. No evidence of MVI or EHS, 3. Not amenable to curative treatment, 4. Child-Pugh Class A, 5. ECOG PS 0 or 1, 6. ALBI grade 1 or 2.
5. Beyond up-to-seven criteria.
6. Disease amenable to TACE or TARE and no contradiction to intra-arterial treatment.
7. Measurable disease by CT or MRI as per RECIST 1.1.
8. No prior systemic therapy or loco-regional therapy for HCC.
9. Adequate hematologic and organ function.
10. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other trial procedures.
11. Women of childbearing potential (CBP) must have confirmed negative serum pregnancy test.
12. Use of highly-effective contraceptive methods in women of CBP and men.
13. Patients with hepatitis C virus (HCV) or hepatitis B virus (HBV) infection are eligible if they meet criteria as defined within the protocol.

Exclusion criteria 12

1. No measurable tumor of a diffuse infiltrative HCC type.
2. Fibrolamellar HCC, sarcomatoid HCC or mixed hepatocellular/ cholangiocarcinoma subtypes.
3. Clinically meaningful ascites.
4. Prior treatment with regorafenib, a PD-1, PD-L1/PD-L2, or cytotoxic T lymphocyte associated protein 4 (CTLA-4) inhibitors, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
5. Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to randomization.
6. Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids.
7. Requirement of systemic treatment with either corticosteroids or other immunosuppressive medications ≤ 14 days prior to randomization.
8. Interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, or clinically significant acute lung diseases.
9. Cardiovascular conditions as defined within the protocol.
10. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed ≤ 2 years before randomization.
11. Persistent proteinuria of NCI-CTCAE v5.0 Grade 3.
12. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS, defined as the time (in months) from the date of randomization until the date of progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed locally by the Investigator using mRECIST.

Secondary endpoints 6

1. PFS: from randomization until PD or death, assessed locally by the Investigator/BICR per RECIST 1.1, and by BICR per mRECIST.
2. OS: from randomization until the date of death.
3. ORR: per RECIST v.1.1 and mRECIST, as per Investigator and BICR assessment.
4. TTUP: from randomization until any protocol criteria are met related to liver function or HCC.
5. DOR: per Investigator assessment or death, in patients who had a best OR of CR or PR.
6. Safety: frequency and severity of AEs and laboratory abnormalities.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Translational Research In Oncology

Sponsor organisation

Translational Research In Oncology

Address

9925 109 St Nw Suite 1100

City

Edmonton

Postcode

T5K 2J8

Country

Canada

Scientific contact point

Organisation

Translational Research In Oncology

Contact name

Trial Project Management

Public contact point

Organisation

Translational Research In Oncology

Contact name

Trial Project Management

Third parties 6

Locations

6 EU/EEA countries · 31 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 144 files

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

Application history

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