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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04551352

Studienbeginn:
Oktober 2020

Letztes Update:
08.06.2021

Wirkstoff:
RO7293583, Tocilizumab, Obinutuzumab, Adalimumab

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Hoffmann-La Roche

Collaborator:
-

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

BP42169 www.roche.com/about_roche/roche_worldwide.htm
Kontakt:
Phone: 888-662-6728 (U.S. Only)
E-Mail: global-roche-genentech-trials@gene.com
» Kontaktdaten anzeigen

Studienlocations
(3 von 17)

Dana Farber Cancer Institute
02215 Boston
United StatesNoch nicht rekrutierend» Google-Maps
Washington University School of Medicine; Center for Clinical Studies
63110 Saint Louis
United StatesNoch nicht rekrutierend» Google-Maps
Columbia University Medical Center; Department of Hematology/Oncology
10032 New York
United StatesNoch nicht rekrutierend» Google-Maps
Memorial Sloan-Kettering Cancer Center
10065 New York
United StatesRekrutierend» Google-Maps
Thomas Jefferson University Hospital;Medical Oncology
19107 Philadelphia
United StatesRekrutierend» Google-Maps
Sarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-Maps
Peter Maccallum Cancer Institute; Clinical Trial Unit
3000 Melbourne
AustraliaRekrutierend» Google-Maps
The Ottawa Hospital - General Campus
K1H 8L6 Ottawa
CanadaRekrutierend» Google-Maps
Princess Margaret Cancer Center
M5G 1Z5 Toronto
CanadaRekrutierend» Google-Maps
Herlev Hospital; Afdeling for Kræftbehandling
2730 Herlev
DenmarkRekrutierend» Google-Maps
Clinica Universitaria de Navarra
31008 Pamplona
SpainRekrutierend» Google-Maps
Hospital Univ Vall d'Hebron; Servicio de Oncologia
08035 Barcelona
SpainRekrutierend» Google-Maps
Clinica Universidad de Navarra Madrid; Servicio de Oncología
28027 Madrid
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
46010 Valencia
SpainRekrutierend» Google-Maps
Universitätsspital Zürich
8091 Zürich
SwitzerlandRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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)):
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.

2. Percentage of Participants with Adverse Events (AEs) (Time Frame - Baseline up to 60 days after last RO7293583 treatment (up to 14 months)):
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.

Secondary outcome:

1. Maximum Concentration (Cmax) of RO7293583 (Time Frame - Up to 14 months)

2. Time of Maximum Concentration (Tmax) of RO7293583 (Time Frame - Up to 14 months)

3. Minimum Concentration (Cmin) of RO7293583 (Time Frame - Up to 14 months)

4. SC Bioavailability (F) of RO7293583 (Time Frame - Up to 14 months)

5. Clearance (CL) or Apparent Clearance (CL/F) of RO7293583 (Time Frame - Up to 14 months)

6. Volume of Distribution at Steady State (Vss) of RO7293583 (Time Frame - Up to 14 months)

7. Area Under the Curve (AUC) of RO7293583 (Time Frame - Up to 14 months)

8. 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).)

9. Change from Baseline in RO7293583 ADA Titer (Time Frame - From baseline until 60 days after last RO7293583 dose (up to 14 months).)

10. Objective Response Rate (ORR) (Time Frame - Baseline up to 13 months):
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.

11. Disease Control Rate (DCR) (Time Frame - Baseline up to 13 months):
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.

12. Duration of Response (DOR) (Time Frame - Baseline up to 13 months):
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.

13. Progression-Free Survival (PFS) (Time Frame - Baseline up to 24 months.):
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.

14. Overall Survival (OS) (Time Frame - Baseline up to 24 months.):
OS is defined as the time from Cycle 1, Day 1 to death from any cause.

Studien-Arme

  • Experimental: 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.
  • Experimental: 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.

Geprüfte Regime

  • RO7293583:
    RO7293583 will be administered at a dose and per schedule as specified for the respective cohort.
  • Tocilizumab (Actemra):
    Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS).
  • Obinutuzumab (Gazyva):
    If implemented, it will be given either on D-7 or D-7 and D-6.
  • Adalimumab (Humira):
    If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583.

Quelle: ClinicalTrials.gov


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