A Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ATG 037 Monotherapy and Combination Therapy With Pembrolizumab in Patients With Advanced Solid Tumors

Locally Advanced or Metastatic Solid Tumors Clinical Trial

Official title:

A Phase I/Ib, Multi-center, Open-label, and Dose-finding Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ATG-037 Monotherapy and Combination Therapy With Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05205109
• Other study ID #: ATG-037-001
• Secondary ID: KEYNOTE-E73
• Status: Recruiting
• Phase: Phase 1
• Start date: June 7, 2022
• Est. completion date: February 28, 2028

Study information

• Verified date: February 2024
• Source: Antengene Corporation
• Contact: Sunny He
• Phone: 187 2152 1865
• Email: sunny.he[@]antengene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors

Description:

This is a Phase I, Multi-center, Open-label, and Dose-finding Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of ATG-037 Monotherapy and Combination Therapy with Pembrolizumab in Patients with Locally Advanced or Metastatic Solid Tumors. Number of subjects : 1. 39-51 subjects for Dose escalation phase part 1 2. Maximum of 18 subjects or Dose escalation phase part 2 3. 24-34 subjects per Dose expansion cohort

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: February 28, 2028
• Est. primary completion date: August 30, 2027
• 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 as of the date of consent.

3. Histological or cytological confirmation of a solid tumor that has relapsed from or refractory to standard therapies.

4. There is at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

5. Estimated life expectancy of a minimum of 12 weeks.

6. Subjects with acquired immune checkpoint inhibitors resistance (objective response or SD>6 months).

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.

8. Females should be using adequate contraceptive measures until 180 days after the end of treatment, should not be breastfeeding.

9. Male subjects should be willing to use barrier contraception, ie condoms, for the duration of the study and 180 days after the final dose of study treatment.

10. Subjects should have adequate organ function.

Exclusion Criteria:

1. Primary central nervous system disease, central nervous system metastatic disease, leptomeningeal disease, metastatic cord compression or carcinomatous meningitis.

2. Prior exposure to a CD73 inhibitor/antibody or adenosine receptor inhibitor.

3. Patients considered to have rapidly progressive disease (from the starting of prior line therapy to disease progression lasting no more than 90 days).

4. 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.

5. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first dose of study treatment. Subject must have recovered from all radiation related toxicity, not requiring corticosteroids.

6. Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures =7 days.

7. Except for alopecia, platinum-induced peripheral neurotoxicity (=Grade 2). Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE 5.0) Grade 1 at the time of ICF signature.

8. Subjects receiving unstable or increasing doses of corticosteroids.

9. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension defined as a blood pressure (BP) =160/100 mmHg despite medical therapy, unstable or uncompensated respiratory and renal disease, active bleeding diseases, allogeneic stem cell transplantation, or any solid organ transplant, etc.

Related Conditions & MeSH terms

• Locally Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ATG-037
Part 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, MK-3475)
Part I: After 2 cycles of ATG-037 monotherapy, eligible participants will receive ATG-037 combination therapy with Keytruda(Pembrolizumab, MK-3475) 200mg/Q3W fixed dose for up to 35 administrations (approximately 2 years). Part II: Keytruda(Pembrolizumab, MK-3475) will be administered from C1.

Locations

Country	Name	City	State
Australia	Southern Oncology Clinical Research Unit	Bedford Park	South Australia
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	One Clinical Research Pty Ltd	Mount Pleasant	Western Australia
Australia	Calvary Mater Newcastle	Sydney	New South Wales
China	Chongqing Cancer Hospital	Chongqing	Chongqing
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
Antengene Therapeutics Limited	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	One year after last patient first dose
Other	Changes in soluble CD73 concentration in serum	To explore potential PDx markers and characterize changes of the immune microenvironment following treatment with ATG-037	One year after last patient first dose
Other	The number and activation status of immune cells in peripheral blood	To explore potential PDx markers and characterize changes of the immune	One year after last patient first dose
Primary	Incidence of adverse events and server adverse events	Will be graded according to the NCI-CTCAE Grading Scale version 5.0.	One year after last patient first dose
Primary	DLT	Number of Participants with Dose Limiting Toxicity	Up to 21 Days
Primary	MTD	Maximum tolerated dose of ATG-037	Up to 21 Days
Primary	RP2D	Recommended phase 2 dose of ATG-037	Up to 21 Days
Secondary	Plasma concentration of ATG-037 and derived PK parameters	To characterize the PK/PDx of ATG-037	One year after last patient first dose
Secondary	Inhibition of CD73 enzymatic activity in plasma	To evaluate the preliminary antitumor activity of ATG-037 monotherapy and combination therapy with pembrolizumab	One year after last patient first dose
Secondary	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	One year after last patient first dose