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

Conditions

• Advanced Liver Cancers

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• 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.

Study Details

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.

Key Dates

Start date

Nov 1, 2020

Status verified

May 2026

Primary completion

Jul 30, 2027

Completion

Sep 30, 2027

Study Design

Enrollment

518 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Stage 1: Atezolizumab + Bevacizumab
  Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + Tiragolumab
  Participants will receive atezolizumab plus bevacizumab plus tiragolumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + Tocilizumab
  Participants will receive atezolizumab plus bevacizumab plus tocilizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + TPST-1120
  Participants will receive atezolizumab plus bevacizumab plus TPST-1120 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Tobemstomig 2100 mg Q2W + Bevacizumab
  Participants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Tobemstomig 600 mg Q3W + Bevacizumab
  Participants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Tobemstomig 1200 mg Q3W + Bevacizumab
  Participants will receive Tobemstomig plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + ADG126
  Participants will receive atezolizumab plus bevacizumab plus ADG126 until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + IO-108 1200 mg Q3W
  Participants will receive atezolizumab plus bevacizumab plus IO-108 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab + NKT2152
  Participants will receive atezolizumab plus bevacizumab plus NKT2152 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.
• Experimental: Stage 1: Atezolizumab + Bevacizumab+ IO-108 1800 mg Q3W
  Participants will receive atezolizumab plus bevacizumab plus IO-108 until unacceptable toxicity or loss of clinical benefit, as determined by the investigator after an integrated assessment of radiographic andbiochemical data, local biopsy results (if available), and clinical status

Primary Outcome Measure

Objective Response Rate (ORR) [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 7-9 years) ]

Central Contacts

• Reference Study ID Number: GO42216 https://forpatients.roche.com/
  888-662-6728 (U.S. and Canada)
  [email protected]

Locations (16)

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