Clinical trial NCT04305249: Safety and Preliminary Efficacy of ATG-017 Monotherapy or Combination Therapy With Nivolumab in Advanced Solid Tumors and Hematological Malignancies
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Solid Tumor
Hematological Malignancy
Lead sponsor: Antengene Corporation
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-03-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

Eligibility criteria: 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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Primary outcomes:
measure: AEs/SAEs
timeFrame: 18 months
Secondary outcomes:
measure: Plasma concentrations
timeFrame: 18 months
measure: Overall Response Rate (ORR)
timeFrame: 18 months
measure: DOR
timeFrame: 18 months
measure: Progression-Free Survival (PFS)
timeFrame: 18 months
Other outcomes:
measure: Level of phospho-p90RSK
timeFrame: 18 months
measure: Level of transcript biomarker
timeFrame: 18 months
measure: Level of phospho-ERK
timeFrame: 18 months
measure: Level of total ERK
timeFrame: 18 months
Locations:
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Randwick
country: Australia
facility: Scientia Clinical Research
city: Sydney
country: Australia
facility: Chris O'Brien Lifehouse
Study officials:
affiliation: Clinical Research Physician
name: Sai Lou, MD
role: STUDY_DIRECTOR
affiliation: Clinical Research Physician
name: Anupa Kudva, MD
role: STUDY_DIRECTOR
affiliation: Executive Director
name: Yiqiang Zhao, MD
role: STUDY_DIRECTOR
References: