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

NCT05205109 | Recruiting Phase 1

• 2 other identifiers: ATG-037-001KEYNOTE-E73
• Study Type: interventional
• Target: 98
• Locations: 2 countries
• Sites: 7

Brief Summary

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

Conditions

Locally Advanced or Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (4)

• 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

• DLT

  Number of Participants with Dose Limiting Toxicity

  Up to 21 Days

• MTD

  Maximum tolerated dose of ATG-037

  Up to 21 Days

• RP2D

  Recommended phase 2 dose of ATG-037

  Up to 21 Days

Secondary Outcomes (3)

• Plasma concentration of ATG-037 and derived PK parameters

  One year after last patient first dose

• Inhibition of CD73 enzymatic activity in plasma

  One year after last patient first dose

• ORR as per RECIST v1.1 and DOR, DCR, PFS, OS evaluated by the investigators

  One year after last patient first dose

Other Outcomes (3)

• Expression of related biomarkers in archived tumor tissue by IHC

  One year after last patient first dose

• Changes in soluble CD73 concentration in serum

  One year after last patient first dose

• The number and activation status of immune cells in peripheral blood

  One year after last patient first dose

Study Arms (1)

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

EXPERIMENTAL

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)

Drug: ATG-037; Drug: KEYTRUDA ®( Pembrolizumab)

Interventions

ATG-037 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.

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

KEYTRUDA ®( Pembrolizumab) 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.

Also known as: MK-3475

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Estimated life expectancy of a minimum of 12 weeks.
• Subjects with acquired immune checkpoint inhibitors resistance (objective response or SD\>6 months).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at ICF signature.
• Females should be using adequate contraceptive measures until 180 days after the end of treatment, should not be breastfeeding.
• 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.
• Subjects should have adequate organ function.

You may not qualify if:

• 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.
• 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.
• Prior major surgery (excluding placement of vascular access) within 28 days of the first dose of study treatment or minor surgical procedures ≤7 days.
• 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.
• 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.
• Subjects receiving unstable or increasing doses of corticosteroids.
• 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.

Sponsors & Collaborators

• Antengene Therapeutics Limited: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (7)

Calvary Mater Newcastle

Sydney, New South Wales, 2298, Australia

RECRUITING

Pindara Private Hospital

Benowa, Queensland, 4217, Australia

RECRUITING

Southern Oncology Clinical Research Unit

Bedford Park, South Australia, 5042, Australia

TERMINATED

Peninsula & South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

RECRUITING

One Clinical Research Pty Ltd

Mount Pleasant, Western Australia, WA6153, Australia

RECRUITING

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400000, China

TERMINATED

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

TERMINATED

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Ganessan Kichenadasse, MD

  Southern Oncology Clinical Research Unit

  PRINCIPAL INVESTIGATOR

• Yi-Long Wu, PhD

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Qing Zhou

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sunny He

CONTACT

187 2152 1865; sunny.he@antengene.com

Ting Liu

CONTACT

ting.liu@antengene.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 24, 2022
• Study Start: June 7, 2022
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: June 9, 2025

Record last verified: 2025-06

Locations

CN (2); AU (5)