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

NCT ID: NCT05205109

Last Updated: 2025-06-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-07
• Study Completion Date: 2028-02-28

Brief Summary

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

Detailed 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

Conditions

Locally Advanced or Metastatic Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ATG-037+Keytruda(Pembrolizumab, MK-3475)

Part I: Dose Escalation Phase of ATG-037 Monotherapy PartII: Dose Escalation Phase and Dose Expansion Phase of ATG-037 in Upfront Combination with Keytruda(Pembrolizumab, MK-3475)

Group Type: EXPERIMENTAL

ATG-037

Intervention Type: DRUG

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)

Intervention Type: DRUG

Part 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.

Interventions

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.

Intervention Type: DRUG

KEYTRUDA ®( Pembrolizumab)

Part 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.

Intervention Type: DRUG

Other Intervention Names

MK-3475

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 as of the date of consent.

3. 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.

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. Received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis.

9. Subjects receiving unstable or increasing doses of corticosteroids.

10. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Antengene Therapeutics Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ganessan Kichenadasse, MD

Role: PRINCIPAL_INVESTIGATOR

Southern Oncology Clinical Research Unit

Yi-Long Wu, PhD

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Qing Zhou

Role: PRINCIPAL_INVESTIGATOR

Guangdong Provincial People's Hospital

Locations

Calvary Mater Newcastle

Sydney, New South Wales, Australia

Site Status: RECRUITING

Pindara Private Hospital

Benowa, Queensland, Australia

Site Status: RECRUITING

Southern Oncology Clinical Research Unit

Bedford Park, South Australia, Australia

Site Status: TERMINATED

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Site Status: RECRUITING

One Clinical Research Pty Ltd

Mount Pleasant, Western Australia, Australia

Site Status: RECRUITING

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status: TERMINATED

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status: TERMINATED

Countries

Australia; China

Central Contacts

Sunny He

Role: CONTACT

sunny.he@antengene.com

187 2152 1865

Ting Liu

Role: CONTACT

ting.liu@antengene.com

Facility Contacts

Janine Lomabard, MD

Role: primary

Janine.Lombard@calvarymater.org.au

Mark Page, PhD

Role: primary

HollandT@ramsayhealth.com.au

+61 7 5588 9040

Albert Goikhman, PhD

Role: primary

ag@paso.com.au

03 9113 1307

NA NA

Role: primary

management@oneclinicalresearch.com.au

Other Identifiers

KEYNOTE-E73

Identifier Type: OTHER

Identifier Source: secondary_id

ATG-037-001

Identifier Type: -

Identifier Source: org_study_id