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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT04551352
Registration number
NCT04551352
Ethics application status
Date submitted
26/08/2020
Date registered
16/09/2020
Titles & IDs
Public title
A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas
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Scientific title
An Open-Label, Multicenter, Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7293583, A TYRP1-Targeting CD3 T-Cell Engager, in Participants With Metastatic Melanoma
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Secondary ID [1]
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2020-000793-18
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Secondary ID [2]
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BP42169
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Cutaneous Melanoma
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Uveal Melanoma
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Mucosal Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - RO7293583
Treatment: Drugs - Tocilizumab
Treatment: Drugs - Obinutuzumab
Treatment: Drugs - Adalimumab
Experimental: Part I: Single Participant Cohorts (IV) - Part I is a dose escalation in single participant cohorts. RO7293583 will be administered intravenously (IV) every three weeks (Q3W). The starting dose will be 0.045mg and the maximum dose explored will be 1.5mg.
Experimental: Part II: Multiple Participant Cohorts (IV/SC) - Multiple ascending dose-escalation of RO7293583 in multiple participant cohorts: The starting-dose for the initiation of the IV dose-escalation will be determined by Part I and RO7293583 will be administered IV or SC every 3 weeks. Dose-escalation will be undertaken based on safety until determination of the MTD or the highest safe dose if MTD is not reached. Fractionated, step up or subcutaneous dosing may be implemented. The maximum dose explored will be 600mg IV and 160mg SC.
Treatment: Drugs: RO7293583
RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.
Treatment: Drugs: Tocilizumab
Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
Treatment: Drugs: Obinutuzumab
If implemented, it will be given either on D-7 or D-7 and D-6.
Treatment: Drugs: Adalimumab
If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of Participants With Dose-Limiting Toxicities (DLTs)
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Assessment method [1]
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Dose-Limiting Toxicities (DLTs) were reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0), except for Cytokine release syndrome (CRS), which will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
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Timepoint [1]
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From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)
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Primary outcome [2]
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Percentage of Participants with Adverse Events (AEs)
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Assessment method [2]
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An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.
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Timepoint [2]
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Baseline up to 60 days after last RO7293583 treatment (up to 14 months)
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Secondary outcome [1]
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Maximum Concentration (Cmax) of RO7293583
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Assessment method [1]
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Timepoint [1]
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Up to 14 months
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Secondary outcome [2]
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Time of Maximum Concentration (Tmax) of RO7293583
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Assessment method [2]
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Timepoint [2]
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Up to 14 months
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Secondary outcome [3]
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Minimum Concentration (Cmin) of RO7293583
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Assessment method [3]
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Timepoint [3]
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Up to 14 months
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Secondary outcome [4]
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SC Bioavailability (F) of RO7293583
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Assessment method [4]
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Timepoint [4]
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Up to 14 months
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Secondary outcome [5]
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Clearance (CL) or Apparent Clearance (CL/F) of RO7293583
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Assessment method [5]
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Timepoint [5]
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Up to 14 months
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Secondary outcome [6]
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Volume of Distribution at Steady State (Vss) of RO7293583
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Assessment method [6]
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Timepoint [6]
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Up to 14 months
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Secondary outcome [7]
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Area Under the Curve (AUC) of RO7293583
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Assessment method [7]
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Timepoint [7]
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Up to 14 months
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Secondary outcome [8]
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Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583
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Assessment method [8]
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Timepoint [8]
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From baseline until 60 days after last RO7293583 dose (up to 14 months).
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Secondary outcome [9]
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Change from Baseline in RO7293583 ADA Titer
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Assessment method [9]
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Timepoint [9]
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From baseline until 60 days after last RO7293583 dose (up to 14 months).
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Secondary outcome [10]
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Objective Response Rate (ORR)
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Assessment method [10]
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ORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions = 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
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Timepoint [10]
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Baseline up to 13 months
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Secondary outcome [11]
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Disease Control Rate (DCR)
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Assessment method [11]
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DCR is defined as the percentage of participants with CR, PR, or stable disease (SD). Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
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Timepoint [11]
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Baseline up to 13 months
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Secondary outcome [12]
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Duration of Response (DOR)
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Assessment method [12]
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DOR is defined as the time from the first occurrence of documented OR to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
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Timepoint [12]
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Baseline up to 13 months
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Secondary outcome [13]
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Progression-Free Survival (PFS)
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Assessment method [13]
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PFS is defined as the time from Cycle 1, Day 1 to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
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Timepoint [13]
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Baseline up to 24 months.
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Secondary outcome [14]
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Overall Survival (OS)
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Assessment method [14]
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OS is defined as the time from Cycle 1, Day 1 to death from any cause.
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Timepoint [14]
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Baseline up to 24 months.
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Eligibility
Key inclusion criteria
* Participants with unresectable stage III or stage IV cutaneous melanoma or participants with unresectable, metastatic uveal or mucosal melanoma for whom SOC is not available or who are intolerant or non-amenable to SOC.
* Participants with cutaneous melanoma need to have known BRAF status.
* Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Availability of a representative tumor specimen that is suitable for determination of TYRP1 status by means of central testing.
* For participants in Part II, willingness to provide mandatory on-treatment biopsies.
* Life expectancy (in the opinion of the Investigator) of =12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
* Absence of rapid disease progression, threat to vital organs or non-irradiated lesions > 2 cm in diameter at critical sites.
* All acute toxic effects of any prior radiotherapy, chemotherapy, targeted or checkpoint inhibitor therapy, or surgical procedure must have resolved to Grade =1 or returned to baseline, except for alopecia (any grade), for Grade 2 clinically controlled sequelae of immune-related toxicities related to checkpoint inhibitor therapy like adrenal insufficiency and hypopituitarism, and for Grade 2 peripheral neuropathy.
* Adequate hematological, liver and renal function.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Participants with a history or clinical evidence of central nervous system (CNS) primary tumors or metastases including leptomeningeal metastases unless they have been previously treated, are asymptomatic, and have had no requirement for steroids or enzyme-inducing anticonvulsants in the last 14 days before screening.
* Participants with another invasive malignancy in the last 2 years.
* Active, acute, or chronic inflammatory diseases of the skin affecting more than 5% of the body surface area. History of Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug rash with eosinophilia and systemic symptoms.
* Participants with defects in the Bruch's membrane of the eye or at risk of such defects. Participants with a history of recurrent uveitis or medical conditions that are associated with frequent uveitis.
* History of or existing damage to inner ear.
* Uncontrolled hypertension.
* Significant cardiovascular disease.
* Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic or other infection, or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to the start of drug administration.
* Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug.
* Major surgery or significant traumatic injury <28 days prior to the first RO7293583 administration or anticipation of the need for major surgery during study treatment.
* Last dose of checkpoint inhibitors, targeted therapies, chemotherapy, immunostimulating or immunosuppressive therapy or other investigational drug <28 days prior to the first RO7293583 administration.
* Prior treatment with a T-cell engaging drug
Specific Exclusion Criteria if Pre-treatment with Obinutuzumab is Implemented:
* Known human immunodeficiency virus (HIV)
* History of progressive multifocal leukoencephalopathy.
* Active Tuberculosis (TB) requiring treatment within 3 years prior to baseline.
* Latent TB diagnosed during Screening.
* Positive test results for human T-lymphotropic virus 1.
Specific Exclusion Criteria if Pre-treatment with Adalimumab is Implemented:
* History of untreated tuberculosis or untreated active infection with mycobacterium tuberculosis.
* Known hypersensitivity to any of the components of adalimumab.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Other
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/10/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
28/07/2022
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Sample size
Target
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Accrual to date
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Final
20
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Peter Maccallum Cancer Institute; Clinical Trial Unit - Melbourne
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Massachusetts
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Country [2]
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United States of America
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State/province [2]
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New York
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Country [3]
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United States of America
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State/province [3]
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Pennsylvania
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Country [4]
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United States of America
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State/province [4]
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Tennessee
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Country [5]
0
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Belgium
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State/province [5]
0
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Edegem
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Country [6]
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Belgium
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State/province [6]
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Leuven
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Country [7]
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Canada
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State/province [7]
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Ontario
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Country [8]
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Denmark
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State/province [8]
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Herlev
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Country [9]
0
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Spain
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State/province [9]
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Navarra
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Country [10]
0
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Spain
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State/province [10]
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Barcelona
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Country [11]
0
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Spain
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State/province [11]
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Madrid
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Country [12]
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Spain
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State/province [12]
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Valencia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a first-in-human, multi-center clinical study to determine the safety, Maximum Tolerated Dose (MTD) and/or Optimal Biological Dose (OBD) as well as the optimal schedule for intravenous (IV) and/or subcutaneous (SC) administrations of RO7293583 with or without obinutuzumab pretreatment, in participants with unresectable metastatic TYRP1-positive melanomas who have progressed on standard of care (SOC) treatment, are intolerant to SOC, or are non-amenable to SOC. This study will include an initial single participant dose-escalation part one followed by a multiple participant dose-escalation part two with the possibility of expansion.
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Trial website
https://clinicaltrials.gov/study/NCT04551352
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT04551352