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

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Brief Title

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

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

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.

Study Phase

Phase 1

Study Type


Primary Outcome

Percentage of Participants With Dose-Limiting Toxicities (DLTs)

Secondary Outcome

 Maximum Concentration (Cmax) of RO7293583


Cutaneous Melanoma



Study Arms / Comparison Groups

 Part I: Single Participant Cohorts (IV)
Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

October 28, 2020

Completion Date

January 15, 2023

Primary Completion Date

January 15, 2023

Eligibility 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

          -  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

          -  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

          -  Known hypersensitivity to any of the components of adalimumab.




18 Years - N/A

Accepts Healthy Volunteers



Clinical Trials, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Hoffmann-La Roche

Study Sponsor

Clinical Trials, Study Director, Hoffmann-La Roche

Verification Date

June 2022