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The study was terminated based on the internal need to re-prioritization the whole pipeline and phase 1 portfolio.
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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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This is a Phase I, multi-center, open-label study of ATG-017 administered orally, alone or in combination with nivolumab in patients with advanced solid tumors and hematological malignancies. The study is composed of two modules: ATG-017 monotherapy (Module A) and ATG-017 in combination with nivolumab (Module B). Both Modules A and B will include Dose Escalation Phase and Dose Expansion Phase.
The dose escalation of ATG 017 will be conducted with intensive safety monitoring to ensure the safety of the patients with solid tumors (Module A and Module B) and hematological malignancies (Module A) harbouring activating alterations in the RAS-MAPK pathway, and will include the continuous and intermittent dosing schedules.
The Dose Expansion Phase will start based on dose level and schedule (continuous or intermittent)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Module A (ATG-017 Monotherapy) | Experimental | Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment. |
|
| Module B (ATG-017+Nivolumab Combination Therapy in Solid Tumors) | Experimental | With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be given at fixed dosing, 480 mg Q4W, on D1 of each cycle. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATG-017 | Drug | Dosing will begin at 5 mg QD ATG-017 as starting dose. A treatment cycle will be 21 days for continuous dosing and 28 days for 7 days on/7 days off intermittent dosing of ATG-017 treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| AEs/SAEs | Toxicity will be graded according to the NCI CTCAE, Version 5.0. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations | Venous blood samples for determination of total concentrations of ATG 017 in plasma to characterise the PK profile of ATG-017 for a particular dose level | 18 months |
| Overall Response Rate (ORR) |
| Measure | Description | Time Frame |
|---|---|---|
| Level of phospho-p90RSK | Blood samples will be analysed for the level of phospho-p90RSK | 18 months |
| Level of transcript biomarker | Blood samples will be analysed for the level of DUSP6 |
Inclusion Criteria:
Exclusion Criteria:
Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.
Prior ATG-017 administration in the present study.
Prior treatment with an ERK1/2 inhibitor.
Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
Patients receiving unstable or increasing doses of corticosteroids.
As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
Active infection including hepatitis B, and/or hepatitis C.
Known history of human immunodeficiency virus (HIV) infection.
Inadequate bone marrow reserve or organ function
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| Name | Affiliation | Role |
|---|---|---|
| Sai Lou, MD | Clinical Research Physician | Study Director |
| Anupa Kudva, MD | Clinical Research Physician | Study Director |
| Yiqiang Zhao, MD | Executive Director | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peter MacCallum Cancer Centre | East Melbourne | Victoria | 3002 | Australia | ||
| Austin Hospital |
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|
| ATG-017+Nivolumab | Drug | With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be specified dose on specified days. |
|
|
To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
| 18 months |
| DOR | Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented | 18 months |
| Progression-Free Survival (PFS) | The time from the first dose date until disease progression or death from any cause | 18 months |
| 18 months |
| Level of phospho-ERK | Blood samples will be analysed for the level of phospho-ERK | 18 months |
| Level of total ERK | Blood samples will be analysed for the level of total ERK | 18 months |
| Heidelberg |
| Victoria |
| 3084 |
| Australia |
| Alfred Hospital | Melbourne | Victoria | 3004 | Australia |
| Scientia Clinical Research | Randwick | Australia |
| Chris O'Brien Lifehouse | Sydney | Australia |
| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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