We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04551352




Registration number
NCT04551352
Ethics application status
Date submitted
26/08/2020
Date registered
16/09/2020
Date last updated
15/04/2021

Titles & IDs
Public title
A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas
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
Secondary ID [1] 0 0
2020-000793-18
Secondary ID [2] 0 0
BP42169
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cutaneous Melanoma 0 0
Uveal Melanoma 0 0
Mucosal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline up to 60 days after last RO7293583 treatment (up to 14 months)
Secondary outcome [1] 0 0
Maximum Concentration (Cmax) of RO7293583
Timepoint [1] 0 0
Up to 14 months
Secondary outcome [2] 0 0
Time of Maximum Concentration (Tmax) of RO7293583
Timepoint [2] 0 0
Up to 14 months
Secondary outcome [3] 0 0
Minimum Concentration (Cmin) of RO7293583
Timepoint [3] 0 0
Up to 14 months
Secondary outcome [4] 0 0
SC Bioavailability (F) of RO7293583
Timepoint [4] 0 0
Up to 14 months
Secondary outcome [5] 0 0
Clearance (CL) or Apparent Clearance (CL/F) of RO7293583
Timepoint [5] 0 0
Up to 14 months
Secondary outcome [6] 0 0
Volume of Distribution at Steady State (Vss) of RO7293583
Timepoint [6] 0 0
Up to 14 months
Secondary outcome [7] 0 0
Area Under the Curve (AUC) of RO7293583
Timepoint [7] 0 0
Up to 14 months
Secondary outcome [8] 0 0
Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583
Timepoint [8] 0 0
From baseline until 60 days after last RO7293583 dose (up to 14 months).
Secondary outcome [9] 0 0
Change from Baseline in RO7293583 ADA Titer
Timepoint [9] 0 0
From baseline until 60 days after last RO7293583 dose (up to 14 months).
Secondary outcome [10] 0 0
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.
Timepoint [10] 0 0
Baseline up to 13 months
Secondary outcome [11] 0 0
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.
Timepoint [11] 0 0
Baseline up to 13 months
Secondary outcome [12] 0 0
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.
Timepoint [12] 0 0
Baseline up to 13 months
Secondary outcome [13] 0 0
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.
Timepoint [13] 0 0
Baseline up to 24 months.
Secondary outcome [14] 0 0
Overall Survival (OS) - OS is defined as the time from Cycle 1, Day 1 to death from any cause.
Timepoint [14] 0 0
Baseline up to 24 months.

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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Peter Maccallum Cancer Institute; Clinical Trial Unit - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
Belgium
State/province [6] 0 0
Edegem
Country [7] 0 0
Belgium
State/province [7] 0 0
Leuven
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Denmark
State/province [9] 0 0
Herlev
Country [10] 0 0
Spain
State/province [10] 0 0
Navarra
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
Spain
State/province [13] 0 0
Valencia
Country [14] 0 0
Switzerland
State/province [14] 0 0
Zürich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT04551352
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
BP42169 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04551352