Safety and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Advanced Solid Tumors and Hematological Malignancies

Solid Tumor Clinical Trial

— ERASER  

Official title:

A Phase I, Open-Label, Multi-Center Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Patients With Advanced Solid Tumors and Hematological Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04305249
• Other study ID #: ATG-017-001
• Status: Recruiting
• Phase: Phase 1
• Start date: August 15, 2020
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Antengene Corporation
• Contact: Ashley Liu
• Phone: 021-23566665
• Email: ting.liu[@]antengene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 211
• Est. completion date: June 30, 2024
• Est. primary completion date: February 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.

2. Aged at least 18 years.

3. Module A: Patient must have a documented activating alteration of the RAS-MAPK pathway.

4. Module B: Dose Escalation Phase: Patient must have a documented activating alteration of the RAS-MAPK pathway; Dose Expansion Phase: Expansion cohorts will be further defined based on information from the Dose Escalation.

5. Histological or cytological confirmation of a solid tumour.

6. Patient with solid tumors must have at least 1 lesion, not previously irradiated.

7. Estimated life expectancy of minimum of 12 weeks.

8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

9. Ability to swallow and retain oral medication.

Exclusion Criteria:

1. Central nervous system metastatic disease, leptomeningeal disease, or metastatic cord compression.

2. Prior ATG-017 administration in the present study.

3. Prior treatment with an ERK1/2 inhibitor.

4. Prior major surgery within 28 days of the first dose of study treatment or minor surgical procedures =7 days.

5. Patients receiving unstable or increasing doses of corticosteroids.

6. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.

7. Active infection including hepatitis B, and/or hepatitis C.

8. Known history of human immunodeficiency virus (HIV) infection.

9. Inadequate bone marrow reserve or organ function

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Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancy
• Neoplasms
• Solid Tumor

Intervention

Drug:
• ATG-017
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.
• ATG-017+Nivolumab
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.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Scientia Clinical Research	Randwick
Australia	Chris O'Brien Lifehouse	Sydney

Sponsors (2)

Lead Sponsor	Collaborator
Antengene Therapeutics Limited	Bristol-Myers Squibb

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Level of phospho-p90RSK	Blood samples will be analysed for the level of phospho-p90RSK	18 months
Other	Level of transcript biomarker	Blood samples will be analysed for the level of DUSP6	18 months
Other	Level of phospho-ERK	Blood samples will be analysed for the level of phospho-ERK	18 months
Other	Level of total ERK	Blood samples will be analysed for the level of total ERK	18 months
Primary	AEs/SAEs	Toxicity will be graded according to the NCI CTCAE, Version 5.0.	18 months
Secondary	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
Secondary	Overall Response Rate (ORR)	To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006	18 months
Secondary	DOR	Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented	18 months
Secondary	Progression-Free Survival (PFS)	The time from the first dose date until disease progression or death from any cause	18 months