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

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

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

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: ATG-037; Drug: KEYTRUDA ®( Pembrolizumab)

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

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sunny He; Phone Number: 187 2152 1865; Email: sunny.he@antengene.com
• Study Contact Backup: Name: Ting Liu; Email: ting.liu@antengene.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2298
      • Recruiting
      • Calvary Mater Newcastle
      • Contact: Janine Lomabard, MD; Email: Janine.Lombard@calvarymater.org.au
  • Queensland
    • Benowa, Queensland, Australia, 4217
      • Recruiting
      • Pindara Private Hospital
      • Contact: Mark Page, PhD; Phone Number: +61 7 5588 9040; Email: HollandT@ramsayhealth.com.au
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Terminated
      • Southern Oncology Clinical Research Unit
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Peninsula & South Eastern Haematology and Oncology Group
      • Contact: Albert Goikhman, PhD; Phone Number: 03 9113 1307; Email: ag@paso.com.au
  • Western Australia
    • Mount Pleasant, Western Australia, Australia, WA6153
      • Recruiting
      • One Clinical Research Pty Ltd
      • Contact: NA NA; Email: management@oneclinicalresearch.com.au
• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Terminated
      • Chongqing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Terminated
      • Guangdong Provincial People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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)

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.; 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.; Other Names: MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of ATG-037 and derived PK parameters	To characterize the PK/PDx of ATG-037	One year after last patient first dose
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Antengene Therapeutics Limited
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Yi-Long Wu, PhD, Guangdong Provincial People's Hospital; Principal Investigator: Qing Zhou, Guangdong Provincial People's Hospital; Principal Investigator: Ganessan Kichenadasse, MD, Southern Oncology Clinical Research Unit

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): June 9, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pembrolizumab
• Other Study ID Numbers: ATG-037-001; KEYNOTE-E73 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No