Clinical trial NCT05205109: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Solid Tumors
Lead sponsor: Antengene Corporation
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-01-24
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Incidence of adverse events and server adverse events
timeFrame: One year after last patient first dose
measure: DLT
timeFrame: Up to 21 Days
measure: MTD
timeFrame: Up to 21 Days
measure: RP2D
timeFrame: Up to 21 Days
Secondary outcomes:
measure: Plasma concentration of ATG-037 and derived PK parameters
timeFrame: One year after last patient first dose
measure: Inhibition of CD73 enzymatic activity in plasma
timeFrame: One year after last patient first dose
measure: ORR as per RECIST v1.1 and DOR, DCR, PFS, OS evaluated by the investigators
timeFrame: One year after last patient first dose
Other outcomes:
measure: Expression of related biomarkers in archived tumor tissue by IHC
timeFrame: One year after last patient first dose
measure: Changes in soluble CD73 concentration in serum
timeFrame: One year after last patient first dose
measure: The number and activation status of immune cells in peripheral blood
timeFrame: One year after last patient first dose
Locations:
city: Sydney
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Mount Pleasant
country: Australia
facility: One Clinical Research Pty Ltd
state: Western Australia
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
Study officials:
affiliation: Southern Oncology Clinical Research Unit
name: Ganessan Kichenadasse, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong Provincial People's Hospital
name: Yi-Long Wu, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong Provincial People's Hospital
name: Qing Zhou
role: PRINCIPAL_INVESTIGATOR
References: