This is a study of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors
Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling, and analyses.
Aged at least 18 years as of the date of consent.
Unresectable Stage III or Stage IV melanoma patients, who have had disease progression on or after at least one prior ICI containing treatment. Patients with mucosal and uveal melanoma types are to be excluded.
There is at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Primary central nervous system disease, central nervous system metastatic disease, leptomeningeal disease, metastatic cord compression or carcinomatous meningitis.
Prior exposure to a CD73 inhibitor/antibody or adenosine receptor inhibitor.
Patients considered to have rapidly progressive disease (from the starting of prior line therapy to disease progression lasting no more than 90 days).
Prior therapy with any chemotherapy, immunotherapy, anticancer agents or investigational products from a previous clinical study within 28 days of the first dose of study treatment or within a period during which the investigational product or systemic anticancer treatment has not been cleared from the body.
Sequential
ATG-037
DrugPart I : ATG-037 will be administered orally once a day (QD) on D-2, then multiple doses of ATG-037 will be administered orally BID for every day from C1D1. A treatment cycle will be defined as 21 days. Part II: ATG-037 will be administered orally BID for every day from C1D1.
KEYTRUDA ®( Pembrolizumab)
DrugPart I: After 2 cycles of ATG-037 monotherapy, eligible participants will receive ATG-037 combination therapy with Keytruda ®(Pembrolizumab) 200mg/Q3W fixed dose for up to 35 administrations (approximately 2 years). Part II: Keytruda ®(Pembrolizumab) will be administered from C1.
Incidence of adverse events and server adverse events
Will be graded according to the NCI-CTCAE Grading Scale version 5.0.
DLT
Number of Participants with Dose Limiting Toxicity
MTD
Maximum tolerated dose of ATG-037
RP2D
Recommended phase 2 dose of ATG-037
Plasma concentration of ATG-037 and derived PK parameters
To characterize the PK/PDx of ATG-037
Inhibition of CD73 enzymatic activity in plasma
To evaluate the preliminary antitumor activity of ATG-037 monotherapy and combination therapy with pembrolizumab
ORR as per RECIST v1.1 and DOR, DCR, PFS, OS evaluated by the investigators
To evaluate the preliminary antitumor activity of ATG-037 monotherapy and combination therapy with pembrolizumab
Expression of related biomarkers in archived tumor tissue by IHC
To explore potential PDx markers and characterize changes of the immune microenvironment following treatment with ATG-037
Changes in soluble CD73 concentration in serum
To explore potential PDx markers and characterize changes of the immune microenvironment following treatment with ATG-037
The number and activation status of immune cells in peripheral blood
To explore potential PDx markers and characterize changes of the immune
Click on the lead sponsor to view all of their trials.
Antengene Therapeutics Limited
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
