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RO7490677

Phase 2

Primary Myelofibrosis | Monoclonal antibody | Oncology |Roche Holding AG|Last Updated: Jan 5, 2022

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindCONTROLLEDDMC
Total Trials1
Total Enrollment125

FDA Designations

No designations recorded

Clinical trial landscape

RO7490677 · 1 trial · 3 indications

Phase 2 1
NCT01981850A Phase 2 Study of RO7490677 In Participants With MyelofibrosisPrimary Myelofibrosis
COMPLETED125 Analytics
PHASE2COMPLETED
A Phase 2 Study of RO7490677 In Participants With Myelofibrosis
Primary MyelofibrosisUnlock trial analytics

Study Endpoints

Primary Endpoints

Stage 1 Main Phase: Overall Response Rate (ORR)
Up until and including completion of 6 cycles. Each cycle is 28 days.

ORR was defined as the percent of participants with a response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. This was defined as those participants who achieved clinical improvement (CI), partial remission (PR), or complete remission (CR) at a post-baseline assessment of treatment response OR had at least stable disease (SD) for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease.

Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)
Up until and including completion of 9 cycles. Each cycle is 28 days.

Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria from baseline to any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.

Stage 1 Main + Open-Label Extension (OLE): ORR
From cycle 1 day 1 up until cycle 6, day 29 (Main Phase). From cycle 7 day 1 up until study discontinuation or study termination, up to 83 cycles (OLE). Each cycle is 28 days.

ORR was defined as the percent of participants with a response according to the IWG-MRT criteria. This was defined as those participants who achieved CI, PR, or CR at a post-baseline assessment of treatment response OR had at least SD for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease. Participants who achieved a clinical benefit in the main phase had the opportunity to remain on treatment. The determination of ORR in the main phase is outlined in the arms description below. Participants who didn't achieve a benefit had the opportunity to switch to a different dosing schedule in the OLE phase. The determination of ORR in the OLE phase is outlined in the arms descriptions below.

Stage 2 Main + Open-Label Extension (OLE): BMRR
From cycle 1 day 1 up until cycle 9 day 29 (main phase). From cycle 10 day 1 up until study discontinuation or study termination, up to 51 cycles (OLE). Each cycle is 28 days.

Defined as the percent of participants with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study. As determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy. Participants in the main phase had the opportunity to remain on treatment (as outlined in the arms description below). Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment and receive PRM-151 10 mg/kg/Q4W (as outlined in the arms description below).

Secondary Endpoints

Stage 1 Main Phase: BMRR
Baseline, Weeks 12 and 24
Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
Baseline, beginning of each cycle (Cycle 2 onward). Each cycle is 28 days.
Stage 2 Main Phase: BMRR
Up until and including completion of 9 cycles. Each cycle is 28 days.
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Stage 1: Cohort 1 WeeklyEXPERIMENTALParticipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 1 Every 4 WeeksEXPERIMENTALParicipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 2 WeeklyEXPERIMENTALParticipants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Stage 1: Cohort 2 Every 4 WeeksEXPERIMENTALParticipants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Stage 2: Cohort 1 0.3mg/kg Every 4 WeeksEXPERIMENTALParticipants will be treated with single agent RO7490677 at a dose of 0.3 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Stage 2: Cohort 2 3mg/kg Every 4 WeeksEXPERIMENTALParticipants will be treated with single agent RO7490677 at a dose of 3.0 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Stage 2: Cohort 3 10mg /kg Every 4 WeeksEXPERIMENTALParticipants will be treated with single agent RO7490677 at a dose of 10 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.

Interventions

NameTypeDescription
RO7490677BIOLOGICALIV infusion
RuxolitinibDRUGIV infusion
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites23

Inclusion Criteria: 1. Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF); 2. Participants must voluntarily sign an ICF; 3. Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF; 4. At least G...

Countries:United StatesCanadaFranceGermanyIsraelItalyNetherlandsUnited Kingdom
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Frequently asked questions about RO7490677

What is RO7490677 used for?

RO7490677 is an investigational monoclonal antibody being studied for the treatment of primary myelofibrosis, a type of bone marrow disorder. It is also being evaluated in related conditions including polycythemia vera and post-essential thrombocythemia myelofibrosis. The drug is currently in Phase 2 clinical development.

Who is developing RO7490677?

RO7490677 is being developed by Roche Holding AG, a multinational healthcare company. Roche is listed on the stock exchange under the ticker RHHBY. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational therapy for myelofibrosis.

What phase is RO7490677 in?

RO7490677 is in Phase 2 clinical development. A Phase 2 study has been completed to evaluate the drug in participants with myelofibrosis. The drug is still investigational and has not been approved by regulatory authorities for commercial use.

What clinical trials is RO7490677 in?

RO7490677 has been studied in a Phase 2 clinical trial registered as NCT01981850. This completed study enrolled 125 participants with primary myelofibrosis, polycythemia vera, and post-essential thrombocythemia myelofibrosis. The trial was conducted in the United States, Canada, France, Germany, Israel, Italy, Netherlands, and the United Kingdom.

Was the RO7490677 clinical trial randomized and blinded?

Yes, the Phase 2 clinical trial of RO7490677 was a randomized, double-blind, controlled study. This design helps reduce bias by randomly assigning participants to treatment groups and keeping both participants and investigators unaware of which treatment was administered.

How does RO7490677 work?

RO7490677 is a monoclonal antibody, a type of biologic therapy that targets specific proteins involved in disease processes. In the context of myelofibrosis, it is being investigated for its potential to interfere with disease-related signaling pathways, though the specific molecular target has not been disclosed.