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

NCT04551352 | Completed Phase 1 FDA Drug

• 2 other identifiers: BP421692020-000793-18
• Study Type: interventional
• Target: 20
• Locations: 6 countries
• Sites: 14

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  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.

  From Day 1 of Cycle 1 up to Day 1 of Cycle 3 (each cycle is 21 days)

• Percentage of Participants with Adverse Events (AEs)

  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.

  Baseline up to 60 days after last RO7293583 treatment (up to 14 months)

Secondary Outcomes (14)

• Maximum Concentration (Cmax) of RO7293583

  Up to 14 months

• Time of Maximum Concentration (Tmax) of RO7293583

  Up to 14 months

• Minimum Concentration (Cmin) of RO7293583

  Up to 14 months

• SC Bioavailability (F) of RO7293583

  Up to 14 months

• Clearance (CL) or Apparent Clearance (CL/F) of RO7293583

  Up to 14 months

Study Arms (2)

Part I: Single Participant Cohorts (IV)

EXPERIMENTAL

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; Drug: Tocilizumab

Part II: Multiple Participant Cohorts (IV/SC)

EXPERIMENTAL

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; Drug: Tocilizumab; Drug: Obinutuzumab; Drug: Adalimumab

Interventions

RO7293583 DRUG

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

Part I: Single Participant Cohorts (IV); Part II: Multiple Participant Cohorts (IV/SC)

Tocilizumab DRUG

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

Also known as: Actemra

Part I: Single Participant Cohorts (IV); Part II: Multiple Participant Cohorts (IV/SC)

Obinutuzumab DRUG

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

Also known as: Gazyva

Part II: Multiple Participant Cohorts (IV/SC)

Adalimumab DRUG

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

Also known as: Humira

Part II: Multiple Participant Cohorts (IV/SC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Thomas Jefferson University Hospital;Medical Oncology

Philadelphia, Pennsylvania, 19107, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Peter Maccallum Cancer Institute; Clinical Trial Unit

Melbourne, Victoria, 3000, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, 2730, Denmark

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

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

Barcelona, 08035, Spain

Location

Clinica Universidad de Navarra Madrid; Servicio de Oncología

Madrid, 28027, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Related Publications (1)

• 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.

  PMID: 38577337 DERIVED

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

tocilizumab; obinutuzumab; Adalimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2020
• First Posted: September 16, 2020
• Study Start: October 28, 2020
• Primary Completion: July 28, 2022
• Study Completion: July 28, 2022
• Last Updated: October 3, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (1); DK (1); CA (2); ES (4); BE (2)