A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients with Advanced Liver Cancers (Morpheus-Liver)

2023-506611-17-00 Protocol GO42216 Phase I and Phase II (Integrated) - Other Ongoing, recruiting

Start 16 Apr 2026 · Status Ongoing, recruiting · 1 EU/EEA countries · 4 sites · Protocol GO42216

Overview

Sponsor-declared trial summary

Phase Phase I and Phase II (Integrated) - Other
Status Ongoing, recruiting
Participants planned 309
Countries 1
Sites 4

Advanced liver cancers

To evaluate the efficacy of immunotherapy-based treatment combinations based on objective response rate (ORR) as determined by the investigator according to RECIST v1.1 and to evaluate the safety of immunotherapy-based treatment combinations

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
16 Apr 2026 → ongoing
Decision date (initial)
2024-05-13
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
F. Hoffmann-La Roche AG

External identifiers

EU CT number
2023-506611-17-00
EudraCT number
2020-001743-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the efficacy of immunotherapy-based treatment combinations based on objective response rate (ORR) as determined by the investigator according to RECIST v1.1 and to evaluate the safety of immunotherapy-based treatment combinations

Secondary objectives 1

  1. To evaluate the efficacy of immunotherapy-based treatment combinations based on progression-free survival (PFS), overall survival (OS) after randomization, OS at specific timepoints, duration of response (DOR), disease control

Conditions and MedDRA coding

Advanced liver cancers

VersionLevelCodeTermSystem organ class
21.1 LLT 10049010 Carcinoma hepatocellular 10029104

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 A Phase Ib/II safety and efficacy study in patients with advanced liver cancers
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in patients with advanced liver cancers. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, modify the patient population, or introduce additional cohorts of patients with other types of advanced primary liver cancer. Eligible patients will initially be randomly assigned to one of several treatment arms, patients who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination.
 Randomised Controlled None Control: Atezolizumab and bevacizumab
Experimental Arm 1: Tiragolumab in combination
Experimental Arm 2: Tocilizumab in combination
Experimental Arm 3: Tocilizumab in combination
Experimental Arm 4: TPST-1120 in combination
Experimental Arm 5: Tobemstomig in combination
Experimental Arm 6: Tobemstomig in combination
Experimental Arm 7: Tobemstomig in combination
Experimental Arm 8: ADG126 in combination
Experimental Arm 9: IO-108 in combination
Experimental Arm 10: IO-108 in combination
Experimental Arm 11: NKT2152 in combination
Experimental Arm 12: NKT2152 in combination

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. 1. Age ≥ 18 years, with an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
  2. 2. Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases criteria in cirrhotic patients
  3. 3. Child-Pugh class A within 7 days prior to randomization
  4. 4. Disease that is not amenable to curative surgical and/or locoregional therapies
  5. 5. No prior systemic treatment (including systemic investigational agents) for HCC
  6. 6. Life expectancy ≥ 3 months, as determined by the investigator and availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing

Exclusion criteria 6

  1. 1. Prior treatment with CD137 agonists or immune checkpoint blockade therapies or inhibitors targeting HIF2alpha
  2. 2. Treatment with investigational therapy within 28 days prior to initiation of study
  3. 3. Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure
  4. 4. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding
  5. 5. A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study
  6. 6. AEs from prior anti-cancer therapy that have not resolved to Grade 1 or better, with the exception of alopecia of any grade

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

  1. 1. ORR (determined by the investigator according to RECIST 1.1)
  2. 2. Incidence, nature, and severity of adverse events and laboratory abnormalities
  3. 3. Change from baseline in vital signs and ECG parameters
  4. 4. Change from baseline in targeted clinical laboratory test results

Secondary endpoints 5

  1. 1. PFS
  2. 2. OS after randomization
  3. 3. OS at specific timepoints
  4. 4. DOR
  5. 5. Disease control

Investigational products

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

Test 11

ADG126

PRD10180375 · Product

Active substance
ADG126
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Not Authorised
MA holder
F. HOFFMANN-LA ROCHE LTD
Paediatric formulation
No
Orphan designation
No

TPST-1120

PRD10886736 · Product

Active substance
TPST-1120
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Authorisation status
Not Authorised
MA holder
F. HOFFMANN-LA ROCHE LTD
Paediatric formulation
No
Orphan designation
No

RO7247669

PRD9859362 · Product

Active substance
RO7247669
Other product name
TOBEMSTOMIG
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Not Authorised
MA holder
F. HOFFMANN-LA ROCHE LTD
Paediatric formulation
No
Orphan designation
No

RO7790118

PRD11262792 · Product

Active substance
3-FLUORO-5-2AR4S-11224-PENTAFLUORO-2A-HYDROXY-22A34-TETRAHYDRO-1H-CYCLOPENTACDINDEN-5-YLOXYBENZONITRILE
Other product name
NKT2152
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Authorisation status
Not Authorised
MA holder
NIKANG THERAPEUTICS, INC.
Paediatric formulation
No
Orphan designation
No

RO7790118

PRD11262794 · Product

Active substance
3-FLUORO-5-2AR4S-11224-PENTAFLUORO-2A-HYDROXY-22A34-TETRAHYDRO-1H-CYCLOPENTACDINDEN-5-YLOXYBENZONITRILE
Other product name
NKT2152
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Authorisation status
Not Authorised
MA holder
NIKANG THERAPEUTICS, INC.
Paediatric formulation
No
Orphan designation
No

RO7790118

PRD11262793 · Product

Active substance
3-FLUORO-5-2AR4S-11224-PENTAFLUORO-2A-HYDROXY-22A34-TETRAHYDRO-1H-CYCLOPENTACDINDEN-5-YLOXYBENZONITRILE
Other product name
NKT2152
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL
Authorisation status
Not Authorised
MA holder
NIKANG THERAPEUTICS, INC.
Paediatric formulation
No
Orphan designation
No

Tecentriq 1 200 mg concentrate for solution for infusion

PRD5434939 · Product

Active substance
Atezolizumab
Substance synonyms
RO5541267
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Authorised
ATC code
L01FF05 — -
Marketing authorisation
EU/1/17/1220/001
MA holder
ROCHE REGISTRATION GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Secondary packaging and labeling for clinical trial use

RO7791094

PRD11262791 · Product

Active substance
Human IGG4 Monoclonal Antibody Against LILRB2
Substance synonyms
IO-108
Other product name
IO-108
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
IV INFUSION
Authorisation status
Not Authorised
MA holder
IMMUNE-ONC THERAPEUTICS, INC.
Paediatric formulation
No
Orphan designation
No

RoActemra 20 mg/mL concentrate for solution for infusion

PRD2154622 · Product

Active substance
Tocilizumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Authorised
ATC code
L04AC07 — -
Marketing authorisation
EU/1/08/492/003
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Secondary packaging and labeling for clinical trial use

Tiragolumab

PRD7846761 · Product

Active substance
Tiragolumab
Pharmaceutical form
CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Not Authorised
MA holder
F. HOFFMANN-LA ROCHE LTD
Paediatric formulation
No
Orphan designation
No

Avastin 25 mg/ml concentrate for solution for infusion.

PRD2153902 · Product

Active substance
Bevacizumab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS INFUSION
Authorisation status
Authorised
ATC code
L01FG01 — -
Marketing authorisation
EU/1/04/300/002
MA holder
ROCHE REGISTRATION GMBH
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Secondary packaging and labeling for clinical trial use

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

213 Total trials 63 Recruiting 141 Ended
Commercial
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 10

OrganisationCity, countryDuties
Pharmaspecific
ORG-100043438
 Champs-Sur-Marne, France Other
Frontage Laboratories Inc.
ORG-100011515
 Exton, United States Laboratory analysis
QPS Netherlands B.V.
ORG-100009393
 Groningen, Netherlands Laboratory analysis
Natera Inc.
ORG-100045860
 Austin, United States Laboratory analysis
Icon Development Solutions LLC
ORG-100012400
 Whitesboro, United States Laboratory analysis
CellCarta
ORG-100039881
 Antwerp, Belgium Laboratory analysis
Almac Clinical Technologies LLC
ORG-100043036
 Souderton, United States Interactive response technologies (IRT)
Precision For Medicine Inc.
ORG-100041895
 Frederick, United States Laboratory analysis
Fortrea Inc.
ORG-100012602
 Durham, United States On site monitoring, Code 12, Other, Code 5, Code 8
Q Squared Solutions LLC
ORG-100043195
 Durham, United States Laboratory analysis

Locations

1 EU/EEA country · 4 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ongoing, recruiting 29 4
Rest of world
New Zealand, Israel, Korea, Republic of, China, Taiwan, United States
 — 280 —

Investigational sites

France

4 sites · Ongoing, recruiting
Centre De Lutte Contre Le Cancer Eugene Marquis
Medical oncology, Avenue La Bataille Flandre Dunkerque, Cs 44229, Rennes Cedex
Institut Gustave Roussy
Department of Therapeutic Innovation and Early Trials, 114 Rue Edouard Vaillant, 94800, Villejuif
Centr Georges Francois Leclerc
Medical oncology, 1 Rue Professeur Marion, 21000, Dijon
Assistance Publique Hopitaux De Marseille
Hepato-Gastroenterology, 264 Rue Saint Pierre, 13005, Marseille

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 2026-04-16 2026-04-16

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Unexpected event UE-51591

Event date
2024-07-11
Date aware
2024-07-12
Submission date
2024-10-15
Member states affected
France
Event description
Please refer to attached document.

Results and documents

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

Documents 27 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol 2023-506611-17-00 Redacted.pdf 8
Protocol (for publication) D4_Patient facing documents_Placeholder.pdf 1
Recruitment arrangements (for publication) K1_Recruitment Arrangements_FR_EN NA
Recruitment arrangements (for publication) K2_Recruitment material Atezolizumab Bevacizumab IO-108 Arm Patient Sheet_FR_FR 1.0
Recruitment arrangements (for publication) K2_Recruitment material Atezolizumab Bevacizumab NKT2152 Arm Patient Sheet_FR_FR 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab ADG126_FR_FR 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab IO108 1200mg_FR_FR_Redacted 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab IO108 1800mg_FR_FR_Redacted 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab NKT2152 RDE-d_FR_FR_Redacted 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab NKT2152 RDE-w_FR_FR_Redacted 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab SAR439459_FR_FR 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab Tiragolumab_FR_FR_Redacted 9.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab Tocilizumab_FR_FR 6.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab TPST-1120_FR_FR_Redacted 7.0
Subject information and informed consent form (for publication) L1_SIS and ICF Atezolizumab Bevacizumab_FR_FR_Redacted 9.0
Subject information and informed consent form (for publication) L1_SIS and ICF COVID-19 Addendum 1_FR_FR 1.0
Subject information and informed consent form (for publication) L1_SIS and ICF Optional biopsies_FR_FR 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Optional RBR_FR_FR 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Optional stool sample_FR_FR 2.0
Subject information and informed consent form (for publication) L1_SIS and ICF Pregnant Partner Authorization Form_FR_FR 7.0
Subject information and informed consent form (for publication) L1_SIS and ICF Pregnant Partner Authorization Form_FR_FR_Redacted 8.0
Subject information and informed consent form (for publication) L1_SIS and ICF RO7247669 600mg Bevacizumab_FR_FR 3.0
Subject information and informed consent form (for publication) L1_SIS and ICF Screening and treatment assignment_FR_FR_Redacted 10.0
Subject information and informed consent form (for publication) L1_SIS and ICF Tobemstomig 1200mg Bevacizumab_FR_FR_Redacted 4.0
Subject information and informed consent form (for publication) L1_SIS and ICF Tobemstomig 2100mg Bevacizumab_FR_FR_Redacted 6.0
Synopsis of the protocol (for publication) D1_Protocol synopsis_ENG 2023-506611-17-00.pdf 2
Synopsis of the protocol (for publication) d1_protocol-synopsis_fr-2023-506611-17-00 2

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-03-01 France Acceptable
2024-05-13
 2024-05-13
2 SUBSTANTIAL MODIFICATION SM-1 2024-08-13 France Acceptable
2024-11-14
 2024-11-14
3 SUBSTANTIAL MODIFICATION SM-2 2024-12-04 France Acceptable
2025-02-12
 2025-02-12
4 SUBSTANTIAL MODIFICATION SM-3 2025-02-26 France Acceptable
2025-04-07
 2025-04-10
5 SUBSTANTIAL MODIFICATION SM-4 2025-07-09 France Acceptable
2025-08-29
 2025-08-29
6 NON SUBSTANTIAL MODIFICATION NSM-1 2025-11-12 France Acceptable
2025-08-29
 2025-11-12
7 NON SUBSTANTIAL MODIFICATION NSM-2 2025-12-04 France Acceptable
2025-08-29
 2025-12-04
8 SUBSTANTIAL MODIFICATION SM-5 2026-01-16 France Acceptable
2026-02-13
 2026-03-05
9 SUBSTANTIAL MODIFICATION SM-6 2026-04-29 France Acceptable
2026-05-26
 2026-05-26

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