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
- Conditions
- Locally Advanced or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT05205109
- Lead Sponsor
- Antengene Therapeutics Limited
- 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 98
- 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.
- Histological or cytological confirmation of a solid tumor that has relapsed from or refractory to standard therapies.
- 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.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ATG-037+Keytruda(Pembrolizumab, MK-3475) KEYTRUDA ®( Pembrolizumab) 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) ATG-037+Keytruda(Pembrolizumab, MK-3475) ATG-037 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)
- Primary Outcome Measures
Name Time Method DLT Up to 21 Days Number of Participants with Dose Limiting Toxicity
MTD Up to 21 Days Maximum tolerated dose of ATG-037
RP2D Up to 21 Days Recommended phase 2 dose of ATG-037
Incidence of adverse events and server adverse events One year after last patient first dose Will be graded according to the NCI-CTCAE Grading Scale version 5.0.
- Secondary Outcome Measures
Name Time Method Plasma concentration of ATG-037 and derived PK parameters One year after last patient first dose To characterize the PK/PDx of ATG-037
ORR as per RECIST v1.1 and DOR, DCR, PFS, OS evaluated by the investigators One year after last patient first dose To evaluate the preliminary antitumor activity of ATG-037 monotherapy and combination therapy with pembrolizumab
Inhibition of CD73 enzymatic activity in plasma One year after last patient first dose To evaluate the preliminary antitumor activity of ATG-037 monotherapy and combination therapy with pembrolizumab
Trial Locations
- Locations (7)
Calvary Mater Newcastle
🇦🇺Sydney, New South Wales, Australia
One Clinical Research Pty Ltd
🇦🇺Mount Pleasant, Western Australia, 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
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China
Chongqing Cancer Hospital
🇨🇳Chongqing, Chongqing, China