Clinical Trials /

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

NCT04551352

Description:

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.

Related Conditions:
  • Cutaneous Melanoma
  • Mucosal Melanoma
  • Uveal Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: BP42169
  • SECONDARY ID: 2020-000793-18
  • NCT ID: NCT04551352

Conditions

  • Cutaneous Melanoma
  • Uveal Melanoma
  • Mucosal Melanoma

Interventions

DrugSynonymsArms
RO7293583Part I: Single Participant Cohorts (IV)
TocilizumabActemraPart I: Single Participant Cohorts (IV)
ObinutuzumabGazyvaPart II: Multiple Participant Cohorts (IV/SC)

Purpose

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 Arms

NameTypeDescriptionInterventions
Part I: Single Participant Cohorts (IV)ExperimentalPart 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.
  • RO7293583
  • Tocilizumab
Part II: Multiple Participant Cohorts (IV/SC)ExperimentalMultiple 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
  • RO7293583
  • Tocilizumab
  • Obinutuzumab

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
             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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Maximum Concentration (Cmax) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:Time of Maximum Concentration (Tmax) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:Minimum Concentration (Cmin) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:SC Bioavailability (F) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:Clearance (CL) or Apparent Clearance (CL/F) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:Volume of Distribution at Steady State (Vss) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure:Area Under the Curve (AUC) of RO7293583
Time Frame:Up to 14 months
Safety Issue:
Description:
Measure: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).
Safety Issue:
Description:
Measure:Change from Baseline in RO7293583 ADA Titer
Time Frame:From baseline until 60 days after last RO7293583 dose (up to 14 months).
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to 13 months
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:Baseline up to 13 months
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Baseline up to 13 months
Safety Issue:
Description: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.
Measure:Progression-Free Survival (PFS)
Time Frame:Baseline up to 24 months.
Safety Issue:
Description: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.
Measure:Overall Survival (OS)
Time Frame:Baseline up to 24 months.
Safety Issue:
Description:OS is defined as the time from Cycle 1, Day 1 to death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

September 10, 2020