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A Study of RO7293583 in Participants With Unresectable Metastatic Tyrosinase Related Protein 1 (TYRP1)-Positive Melanomas

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ClinicalTrials.gov Identifier: NCT04551352
Recruitment Status : Recruiting
First Posted : September 16, 2020
Last Update Posted : September 5, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

Condition or disease Intervention/treatment Phase
Cutaneous Melanoma Uveal Melanoma Mucosal Melanoma Drug: RO7293583 Drug: Tocilizumab Drug: Obinutuzumab Drug: Adalimumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 310 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 28, 2020
Estimated Primary Completion Date : September 15, 2023
Estimated Study Completion Date : September 15, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
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.
Drug: RO7293583
RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.

Drug: Tocilizumab
Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
Other Name: Actemra

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.
Drug: RO7293583
RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.

Drug: Tocilizumab
Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
Other Name: Actemra

Drug: Obinutuzumab
If implemented, it will be given either on D-7 or D-7 and D-6.
Other Name: Gazyva

Drug: Adalimumab
If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.
Other Name: Humira




Primary Outcome Measures :
  1. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days) ]
    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.

  2. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to 60 days after last RO7293583 treatment (up to 14 months) ]
    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.


Secondary Outcome Measures :
  1. Maximum Concentration (Cmax) of RO7293583 [ Time Frame: Up to 14 months ]
  2. Time of Maximum Concentration (Tmax) of RO7293583 [ Time Frame: Up to 14 months ]
  3. Minimum Concentration (Cmin) of RO7293583 [ Time Frame: Up to 14 months ]
  4. SC Bioavailability (F) of RO7293583 [ Time Frame: Up to 14 months ]
  5. Clearance (CL) or Apparent Clearance (CL/F) of RO7293583 [ Time Frame: Up to 14 months ]
  6. Volume of Distribution at Steady State (Vss) of RO7293583 [ Time Frame: Up to 14 months ]
  7. Area Under the Curve (AUC) of RO7293583 [ Time Frame: Up to 14 months ]
  8. 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). ]
  9. Change from Baseline in RO7293583 ADA Titer [ Time Frame: From baseline until 60 days after last RO7293583 dose (up to 14 months). ]
  10. Objective Response Rate (ORR) [ Time Frame: Baseline up to 13 months ]
    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.

  11. Disease Control Rate (DCR) [ Time Frame: Baseline up to 13 months ]
    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.

  12. Duration of Response (DOR) [ Time Frame: Baseline up to 13 months ]
    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.

  13. Progression-Free Survival (PFS) [ Time Frame: Baseline up to 24 months. ]
    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.

  14. Overall Survival (OS) [ Time Frame: Baseline up to 24 months. ]
    OS is defined as the time from Cycle 1, Day 1 to death from any cause.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04551352


Contacts
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Contact: BP42169 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Thomas Jefferson University Hospital;Medical Oncology Recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Australia, Victoria
Peter Maccallum Cancer Institute; Clinical Trial Unit Recruiting
Melbourne, Victoria, Australia, 3000
Belgium
UZ Antwerpen Recruiting
Edegem, Belgium, 2650
UZ Leuven Gasthuisberg Recruiting
Leuven, Belgium, 3000
Canada, Ontario
The Ottawa Hospital - General Campus Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Princess Margaret Cancer Center Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Denmark
Herlev Hospital; Afdeling for Kræftbehandling Recruiting
Herlev, Denmark, 2730
Spain
Clinica Universitaria de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Hospital Univ Vall d'Hebron; Servicio de Oncologia Recruiting
Barcelona, Spain, 08035
Clinica Universidad de Navarra Madrid; Servicio de Oncología Active, not recruiting
Madrid, Spain, 28027
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia Recruiting
Valencia, Spain, 46010
Switzerland
Universitätsspital Zürich Recruiting
Zürich, Switzerland, 8091
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04551352    
Other Study ID Numbers: BP42169
2020-000793-18 ( EudraCT Number )
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: September 5, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adalimumab
Obinutuzumab
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents