Health TrialsbyHealthPanel

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

ConditionAdvanced Liver Cancers
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorHoffmann-La Roche

About this trial

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants 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 participant population, or introduce additional cohorts of participants with other types of advanced primary liver cancer.

Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization

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

Child-Pugh class A within 7 days prior to randomization

Disqualifiers

Prior treatment with CD137 agonists or immune checkpoint blockade therapies or inhibitors targeting HIF2a

Treatment with investigational therapy within 28 days prior to initiation of study

Treatment with locoregional therapy to liver within 28 days prior to initiation of study, or non-recovery from side effects of any such procedure

Untreated or incompletely treated esophageal and/or gastric varices with bleeding or at high risk for bleeding

Trial design

Design model

Parallel

Treatments tested in this trial

  • Atezolizumab

    Drug

    Atezolizumab will be administered at a dose of 1200 mg by IV on Day 1 of each 21 day cycle.

  • Bevacizumab 15 mg/kg

    Drug

    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1 of each 21 day cycle.

  • Tiragolumab

    Drug

    Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.

  • Tocilizumab

    Drug

    Tocilizumab will be administered at a dose of 8 mg/kg by IV infusion on Day 1 of each 21 day cycle.

  • TPST-1120

    Drug

    TPST-1120 will be administered at a dose of 1200 mg by mouth on Days 1-21 of each 21 day cycle.

  • Tobemstomig 2100 mg

    Drug

    Tobemstomig will be administered at a dose of 2100 mg by IV infusion on Days 1 and 15 of each 28 day cycle.

  • Bevacizumab 10 mg/kg

    Drug

    Bevacizumab will be administered at a dose of 10 mg/kg by IV infusion on Days 1 and 15 of each 28 day cycle.

  • Tobemstomig 600 mg

    Drug

    Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1 of each 21 day cycle.

  • Tobemstomig 1200 mg

    Drug

    Tobemstomig will be administered at a dose of 1200 mg every 3 weeks.

  • ADG126

    Drug

    ADG126 will be administered at a dose of 6 mg/kg by IV infusion on Day 1 of every other cycle (cycle length = 21 days).

  • IO-108 1800 mg

    Drug

    IO-108 will be administered at a dose 1800 mg by IV infusion on Day 1 of each 21 day cycle.

  • NKT2152

    Drug

    NKT2152 will be administered by mouth.

  • IO-108 1200 mg

    Drug

    IO-108 will be administered at a dose 1200 mg by IV infusion on Day 1 of each 21 day cycle.

Treatment groups

518 Participants
are divided into 11 treatment groups

11

Treatment groups

See each treatment group below.

Group A: Stage 1: Atezolizumab + BevacizumabActive comparator 2 interventions
Group B: Stage 1: Atezolizumab + Bevacizumab + TiragolumabExperimental treatment 3 interventions
Group C: Stage 1: Atezolizumab + Bevacizumab + TocilizumabExperimental treatment 3 interventions
Group D: Stage 1: Atezolizumab + Bevacizumab + TPST-1120Experimental treatment 3 interventions
Group E: Stage 1: Tobemstomig 2100 mg Q2W + BevacizumabExperimental treatment 3 interventions
Group F: Stage 1: Tobemstomig 600 mg Q3W + BevacizumabExperimental treatment 2 interventions
Group G: Stage 1: Tobemstomig 1200 mg Q3W + BevacizumabExperimental treatment 2 interventions
Group H: Stage 1: Atezolizumab + Bevacizumab + ADG126Experimental treatment 3 interventions
Group I: Stage 1: Atezolizumab + Bevacizumab + IO-108 1200 mg Q3WExperimental treatment 3 interventions
Group J: Stage 1: Atezolizumab + Bevacizumab + NKT2152Experimental treatment 3 interventions
Group K: Stage 1: Atezolizumab + Bevacizumab+ IO-108 1800 mg Q3WExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Objective Response Rate (ORR)

ORR, defined as the proportion of participants with a complete response or partial response on two consecutive occasions \>=4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.

Time frame
From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years)

Secondary outcomes

1

Progression Free Survival (PFS)

PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.

Time frame
Randomization to first occurrence of disease progression or death from any cause in Stage 1 (up to approximately 7-9 years)
2

Overall Survival (OS)

OS after randomization, defined as the time from randomization to death from any cause.

Time frame
Randomization to death from any cause (up to approximately 7-9 years)
3

OS at Specific Timepoints

OS at a specific timepoint, such as Month 6

Time frame
Randomization to a specific timepoint, such as Month 6
4

Duration of Response (DOR)

DOR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.

Time frame
First occurrence of a documented objective response to disease progression or death (up to approximately 7-9 years)

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Hoffmann-La Roche

Lead sponsor

Adagene Inc

Collaborator

Tempest Therapeutics

Collaborator

NiKang Therapeutics, Inc.

Collaborator

Immune-Onc Therapeutics

Collaborator

Source ClinicalTrials.gov
Apply now