A Study Evaluating the Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients with Surgically Resectable Hepatocellular Carcinoma (Morpheus-Neo HCC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Nov 2023 → 24 Oct 2025

Decision date (initial)

2023-10-30

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of neoadjuvant immunotherapy-based treatment
combinations based on the major pathologic response (MPR) rate

Secondary objectives 3

1. To evaluate the efficacy of neoadjuvant immunotherapy-based treatment combinations based on the pathologic complete response (pCR) rate, relapse-free survival (RFS), event-free survival (EFS), overall survival (OS), objective response rate (ORR), proportion of participants downstaged to within Milan criteria, and R0 resection rate
2. To evaluate the safety and tolerability of neoadjuvant immunotherapy-based treatment combinations based on the incidence, nature, and severity of adverse events, serious adverse events, and immune-related adverse events
3. To assess surgical feasibility, outcomes, morbidity, and mortality in participants receiving neoadjuvant immunotherapy-based treatment combinations based on the proportion of participants with delayed or canceled surgery due to treatment-related adverse events, length of surgical delay, duration of surgery, length of hospital stay, surgical approach, extent of surgery, intraoperative blood loss, need for intraoperative blood transfusion, post-operative surgical complication rates according to Clavien-Dindo surgical classification, and post-operative mortality

Conditions and MedDRA coding

Hepatocellular Carcinoma (Morpheus-Neo HCC)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of HCC confirmed either histologically or clinically according to American Association for the Study of Liver Diseases (AASLD) criteria for patients with cirrhosis
2. HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant
3. Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as determined by the investigator
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
5. Child-Pugh Class A within 7 days prior to randomization
6. No prior locoregional or systemic treatment for HCC

Exclusion criteria 5

1. Presence of extrahepatic disease or macrovascular invasion
2. Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC
3. History of hepatic encephalopathy
4. Moderate or severe ascites
5. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MPR rate

Secondary endpoints 11

1. pCR rate
2. RFS
3. EFS
4. OS
5. ORR
6. Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization)
7. R0 resection rate (proportion of resected participants obtaining an R0 resection)
8. Incidence, nature, and severity of adverse events, serious adverse events, and immune-related adverse events [severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0); severity of cytokine release syndrome (CRS) determined according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading Scale]
9. Proportion of participants with delayed or canceled surgery due to treatment-related adverse events, as well as length of surgical delay, duration of surgery, length of hospital stay, surgical approach, extent of surgery, intraoperative blood loss, and need for intraoperative blood transfusion
10. Post-operative surgical complication rates according to the Clavien- Dindo surgical classification
11. Post-operative mortality

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 5

Locations

4 EU/EEA countries · 15 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 5 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