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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.
Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
If implemented, it will be given either on D-7 or D-7 and D-6.
If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
Thomas Jefferson University Hospital;Medical Oncology
Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Peter Maccallum Cancer Institute; Clinical Trial Unit
Melbourne, Victoria, Australia
UZ Antwerpen
Edegem, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
The Ottawa Hospital - General Campus
Ottawa, Ontario, Canada
Princess Margaret Cancer Center
Toronto, Ontario, Canada
Herlev Hospital; Afdeling for Kræftbehandling
Herlev, Denmark
...and 4 more locations
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
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.
Time frame: From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)
Percentage of Participants with Adverse Events (AEs)
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.
Time frame: Baseline up to 60 days after last RO7293583 treatment (up to 14 months)
Maximum Concentration (Cmax) of RO7293583
Time frame: Up to 14 months
Time of Maximum Concentration (Tmax) of RO7293583
Time frame: Up to 14 months
Minimum Concentration (Cmin) of RO7293583
Time frame: Up to 14 months
SC Bioavailability (F) of RO7293583
Time frame: Up to 14 months
Clearance (CL) or Apparent Clearance (CL/F) of RO7293583
Time frame: Up to 14 months
Volume of Distribution at Steady State (Vss) of RO7293583
Time frame: Up to 14 months
Area Under the Curve (AUC) of RO7293583
Time frame: Up to 14 months
Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583
Time frame: From baseline until 60 days after last RO7293583 dose (up to 14 months).
Change from Baseline in RO7293583 ADA Titer
Time frame: From baseline until 60 days after last RO7293583 dose (up to 14 months).
Objective Response Rate (ORR)
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.
Time frame: Baseline up to 13 months
Disease Control Rate (DCR)
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.
Time frame: Baseline up to 13 months
Duration of Response (DOR)
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.
Time frame: Baseline up to 13 months
Progression-Free Survival (PFS)
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.
Time frame: Baseline up to 24 months.
Overall Survival (OS)
OS is defined as the time from Cycle 1, Day 1 to death from any cause.
Time frame: Baseline up to 24 months.
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