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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04551352
Other study ID # BP42169
Secondary ID 2020-000793-18
Status Completed
Phase Phase 1
First received
Last updated
Start date October 28, 2020
Est. completion date July 28, 2022

Study information

Verified date September 2022
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 20
Est. completion date July 28, 2022
Est. primary completion date July 28, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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. 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.

Study Design


Intervention

Drug:
RO7293583
RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.
Tocilizumab
Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
Obinutuzumab
If implemented, it will be given either on D-7 or D-7 and D-6.
Adalimumab
If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.

Locations

Country Name City State
Australia Peter Maccallum Cancer Institute; Clinical Trial Unit Melbourne Victoria
Belgium UZ Antwerpen Edegem
Belgium UZ Leuven Gasthuisberg Leuven
Canada The Ottawa Hospital - General Campus Ottawa Ontario
Canada Princess Margaret Cancer Center Toronto Ontario
Denmark Herlev Hospital; Afdeling for Kræftbehandling Herlev
Spain Vall d´Hebron Institute of Oncology (VHIO), Barcelona Barcelona
Spain Clinica Universidad de Navarra Madrid; Servicio de Oncología Madrid
Spain Clinica Universitaria de Navarra Pamplona Navarra
Spain Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia Valencia
United States Dana Farber Cancer Institute Boston Massachusetts
United States Sarah Cannon Research Institute Nashville Tennessee
United States Memorial Sloan-Kettering Cancer Center New York New York
United States Thomas Jefferson University Hospital;Medical Oncology Philadelphia Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Denmark,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)
Primary 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. Baseline up to 60 days after last RO7293583 treatment (up to 14 months)
Secondary Maximum Concentration (Cmax) of RO7293583 Up to 14 months
Secondary Time of Maximum Concentration (Tmax) of RO7293583 Up to 14 months
Secondary Minimum Concentration (Cmin) of RO7293583 Up to 14 months
Secondary SC Bioavailability (F) of RO7293583 Up to 14 months
Secondary Clearance (CL) or Apparent Clearance (CL/F) of RO7293583 Up to 14 months
Secondary Volume of Distribution at Steady State (Vss) of RO7293583 Up to 14 months
Secondary Area Under the Curve (AUC) of RO7293583 Up to 14 months
Secondary Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583 From baseline until 60 days after last RO7293583 dose (up to 14 months).
Secondary Change from Baseline in RO7293583 ADA Titer From baseline until 60 days after last RO7293583 dose (up to 14 months).
Secondary 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. Baseline up to 13 months
Secondary 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. Baseline up to 13 months
Secondary 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. Baseline up to 13 months
Secondary 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. Baseline up to 24 months.
Secondary Overall Survival (OS) OS is defined as the time from Cycle 1, Day 1 to death from any cause. Baseline up to 24 months.
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