Clinical trial NCT04551352: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cutaneous Melanoma
Uveal Melanoma
Mucosal Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-09-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

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.

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Baseline up to 60 days after last RO7293583 treatment (up to 14 months)
Secondary outcomes:
measure: Maximum Concentration (Cmax) of RO7293583
timeFrame: Up to 14 months
measure: Time of Maximum Concentration (Tmax) of RO7293583
timeFrame: Up to 14 months
measure: Minimum Concentration (Cmin) of RO7293583
timeFrame: Up to 14 months
measure: SC Bioavailability (F) of RO7293583
timeFrame: Up to 14 months
measure: Clearance (CL) or Apparent Clearance (CL/F) of RO7293583
timeFrame: Up to 14 months
measure: Volume of Distribution at Steady State (Vss) of RO7293583
timeFrame: Up to 14 months
measure: Area Under the Curve (AUC) of RO7293583
timeFrame: Up to 14 months
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583
timeFrame: From baseline until 60 days after last RO7293583 dose (up to 14 months).
measure: Change from Baseline in RO7293583 ADA Titer
timeFrame: From baseline until 60 days after last RO7293583 dose (up to 14 months).
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 13 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 13 months
measure: Duration of Response (DOR)
timeFrame: Baseline up to 13 months
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to 24 months.
measure: Overall Survival (OS)
timeFrame: Baseline up to 24 months.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital;Medical Oncology
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Institute; Clinical Trial Unit
state: Victoria
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Herlev
country: Denmark
facility: Herlev Hospital; Afdeling for Kræftbehandling
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Vall d´Hebron Institute of Oncology (VHIO), Barcelona
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra Madrid; Servicio de Oncología
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: