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

Phase 1

Terminated

• Conditions: Solid Tumor; Hematological Malignancy
• Interventions: Drug: ATG-017; Drug: ATG-017+Nivolumab

• Registration Number: NCT04305249
• Lead Sponsor: Antengene Therapeutics Limited

Brief 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.

Detailed 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)

Study Timeline

• Study First Submitted: 2020-03-05
• Study First Submitted QC: 2020-03-10
• Study First Posted: 2020-03-12
• Study Start: 2020-08-15
• Status Verified: 2024-04
• Primary Completion: 2024-04-11
• Study Completion: 2024-05-24
• Last Update Submitted: 2024-07-22
• Last Update Posted: 2024-07-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Module A (ATG-017 Monotherapy)	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.
Module B (ATG-017+Nivolumab Combination Therapy in Solid Tumors)	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 given at fixed dosing, 480 mg Q4W, on D1 of each cycle.

Primary Outcome Measures

Name	Time	Method
AEs/SAEs	18 months	Toxicity will be graded according to the NCI CTCAE, Version 5.0.

Secondary Outcome Measures

Name	Time	Method
Plasma concentrations	18 months	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
Overall Response Rate (ORR)	18 months	To determine the overall response rate according to RECIST1.1, Chenson 2014, IWG 2003 and 2006
DOR	18 months	Duration of time from first occurrence of CR or PR until the first date that disease progression is objectively documented
Progression-Free Survival (PFS)	18 months	The time from the first dose date until disease progression or death from any cause

Trial Locations

Locations (5)

Chris O'Brien Lifehouse; 🇦🇺 Sydney, Australia

Scientia Clinical Research; 🇦🇺 Randwick, Australia

Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia

Austin Hospital; 🇦🇺 Heidelberg, Victoria, Australia

Peter MacCallum Cancer Centre; 🇦🇺 East Melbourne, Victoria, Australia