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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000793-18 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO7293583 | Drug | RO7293583 will be administered at a dose and per schedule as specified for the respective cohort. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Specific Exclusion Criteria if Pre-treatment with Obinutuzumab is Implemented:
Specific Exclusion Criteria if Pre-treatment with Adalimumab is Implemented:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dana Farber Cancer Institute | Boston | Massachusetts | 02215 | United States | ||
| Memorial Sloan-Kettering Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38577337 | Derived | 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. |
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| Tocilizumab | Drug | Tocilizumab will be administered as required for the management of severe cytokine release syndrome (CRS). |
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| Obinutuzumab | Drug | If implemented, it will be given either on D-7 or D-7 and D-6. |
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| Adalimumab | Drug | If implemented, it will be given as a single dose approximately 6 days prior to the first dose of RO7293583. |
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| 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 |
| Volume of Distribution at Steady State (Vss) of RO7293583 | Up to 14 months |
| Area Under the Curve (AUC) of RO7293583 | Up to 14 months |
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7293583 | From baseline until 60 days after last RO7293583 dose (up to 14 months). |
| Change from Baseline in RO7293583 ADA Titer | From baseline until 60 days after last RO7293583 dose (up to 14 months). |
| Objective Response Rate (ORR) | 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. | Baseline up to 13 months |
| Disease Control Rate (DCR) | 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. | Baseline up to 13 months |
| Duration of Response (DOR) | 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. | Baseline up to 13 months |
| Progression-Free Survival (PFS) | 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. | Baseline up to 24 months. |
| Overall Survival (OS) | OS is defined as the time from Cycle 1, Day 1 to death from any cause. | Baseline up to 24 months. |
| New York |
| New York |
| 10065 |
| United States |
| Thomas Jefferson University Hospital;Medical Oncology | Philadelphia | Pennsylvania | 19107 | United States |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Peter Maccallum Cancer Institute; Clinical Trial Unit | Melbourne | Victoria | 3000 | Australia |
| UZ Antwerpen | Edegem | 2650 | Belgium |
| UZ Leuven Gasthuisberg | Leuven | 3000 | Belgium |
| The Ottawa Hospital - General Campus | Ottawa | Ontario | K1H 8L6 | Canada |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 1Z5 | Canada |
| Herlev Hospital; Afdeling for Kræftbehandling | Herlev | 2730 | Denmark |
| Clinica Universitaria de Navarra | Pamplona | Navarre | 31008 | Spain |
| Vall d´Hebron Institute of Oncology (VHIO), Barcelona | Barcelona | 08035 | Spain |
| Clinica Universidad de Navarra Madrid; Servicio de Oncología | Madrid | 28027 | Spain |
| Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | 46010 | Spain |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| D000098943 | Uveal Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014604 | Uveal Neoplasms |
| D005134 | Eye Neoplasms |
| D005128 | Eye Diseases |
| D014603 | Uveal Diseases |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
| C543332 | obinutuzumab |
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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