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

NCT ID: NCT04551352

Last Updated: 2022-10-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-28
• Study Completion Date: 2022-07-28

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.

Conditions

Cutaneous Melanoma; Uveal Melanoma; Mucosal Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

RO7293583

Intervention Type: DRUG

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

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).

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.

Group Type: EXPERIMENTAL

RO7293583

Intervention Type: DRUG

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

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).

Obinutuzumab

Intervention Type: DRUG

If implemented, it will be given either on D-7 or D-7 and D-6.

Adalimumab

Intervention Type: DRUG

If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.

Interventions

RO7293583

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

Intervention Type: DRUG

Tocilizumab

Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).

Intervention Type: DRUG

Obinutuzumab

If implemented, it will be given either on D-7 or D-7 and D-6.

Intervention Type: DRUG

Adalimumab

If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.

Intervention Type: DRUG

Other Intervention Names

Actemra; Gazyva; Humira

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

• 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.

• History of untreated tuberculosis or untreated active infection with mycobacterium tuberculosis.
• Known hypersensitivity to any of the components of adalimumab.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Thomas Jefferson University Hospital;Medical Oncology

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Peter Maccallum Cancer Institute; Clinical Trial Unit

Melbourne, Victoria, Australia

UZ Antwerpen

Edegem, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, , Denmark

Clinica Universitaria de Navarra

Pamplona, Navarre, Spain

Vall d´Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, , Spain

Clinica Universidad de Navarra Madrid; Servicio de Oncología

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Countries

United States; Australia; Belgium; Canada; Denmark; Spain

References

Spreafico A, Couselo EM, Irmisch A, Bessa J, Au-Yeung G, Bechter O, Svane IM, Sanmamed MF, Gambardella V, McKean M, Callahan M, Dummer R, Klein C, Umana P, Justies N, Heil F, Fahrni L, Opolka-Hoffmann E, Waldhauer I, Bleul C, Staack RF, Karanikas V, Fowler S. Phase 1, first-in-human study of TYRP1-TCB (RO7293583), a novel TYRP1-targeting CD3 T-cell engager, in metastatic melanoma: active drug monitoring to assess the impact of immune response on drug exposure. Front Oncol. 2024 Mar 21;14:1346502. doi: 10.3389/fonc.2024.1346502. eCollection 2024.

Reference Type: DERIVED

PMID: 38577337 (View on PubMed)

Other Identifiers

2020-000793-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BP42169

Identifier Type: -

Identifier Source: org_study_id