Clinical trial NCT05614258: Study of ADG206 in Subjects With Advanced/Metastatic Solid Tumors
Official title: A First-in-Human (FIH), Open-Label, Phase 1 Study of ADG206, a CD137 Agonist Antibody, in Subjects With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Lead sponsor: Adagene Inc
Sponsor class: INDUSTRY
First posted: 2022-11-14
Enrollment: 21
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: ADG206 is an activatable prodrug form of a fully human monoclonal antibody (mAb) of the immunoglobulin G1 (IgG1) subclass that specifically targets cluster of differentiation 137 (CD137) (also known as 4-1BB) as a co-stimulatory receptor agonist for the treatment of advanced malignancies.

Detailed description: This is a FIH, Phase 1, open-label, multicenter, sequential dose escalation study to evaluate the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ADG206 in subjects with advanced/metastatic malignancies.

Primary Objective of the study: To assess safety and tolerability at increasing dose levels of ADG206 in subjects with advanced/metastatic solid tumors who have exhausted their treatment alternatives.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
* Subjects with advanced or metastatic solid tumors (except thymic tumors), which have progressed after all standard therapies, or no further standard therapies exists.
* At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
* Adequate organ function.
* Woman of childbearing potential must agree to use 2 methods of acceptable contraception from screening until 6 months after the last dose of study drug.
* Male subjects who are sexually active with a female partner of childbearing potential must agree to use a barrier contraception.

Exclusion Criteria:

* Subjects within washout period of other anti-tumor therapies. .
* History of prior malignancy other than the cancer under treatment in the study.
* Major trauma or major surgery within 4 weeks before the first dose of study drug.
* Serious nonhealing wound, ulcer, or bone fracture.
* History of significant immune-mediated AE.
* Central nervous system (CNS) disease involvement.
* Any evidence of underlying severe liver dysfunction.
* Prior organ allograft transplantations or allogeneic bone marrow, cord blood or peripheral blood stem cell transplantation.
* Clinically significant cardiac disease with insufficient cardiac function.
* Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
* Known positive test result for human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS).
* Infection of hepatitis B virus (HBV), or hepatitis C virus (HCV) (unless the disease is clinically controlled) .
* History or risk of autoimmune disease.
* Subjects with active severe lung infection or with a history of interstitial lung diseases, noninfectious pneumonitis, active pulmonary tuberculosis, or evidence of active pneumonitis. Clinically significant and unmanageable ascites defined as requiring constant therapeutic paracentesis.
* Any serious underlying issue that would limit compliance with study requirements, impair the ability of the subject to understand informed consent.
* Known hypersensitivity, allergies, or intolerance to immunoglobulins or to any excipient contained in ADG206.
* Pregnant, lactating, or breastfeeding.

Primary outcomes:
measure: Number of participants experiencing dose-limiting toxicities escalating dose levels
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Number of participants with adverse events (AE)
timeFrame: At the end of 90 days post last dose (each cycle is 21 days)
measure: Maximum administered dose (MAD) of ADG206
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Maximum tolerated dose (MTD) of ADG 206
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Recommended Phase 2 dose (RP2D) of ADG206
timeFrame: At the end of the last dose (each cycle is 21 days)
Secondary outcomes:
measure: The area under the curve (AUC) of plasma concentration of drug
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Immunogenicity endpoints include antidrug antibodies (ADAs)
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Maximum concentration (Cmax)
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Time to maximum plasma concentration (Tmax)
timeFrame: At the end of the last dose (each cycle is 21 days)
measure: Lowest plasma concentration (C[trough])
timeFrame: At the end of the last dose (each cycle is 21 days)
Other outcomes:
Locations:
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
state: South Australia
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
Study officials:
References: