Clinical trial NCT04645069: ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors
Official title: A First-in-Human (FIH), Open-Label, Phase 1/2 Dose Escalation and Expansion Study of ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Patients With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced/Metastatic Solid Tumors
Keywords: Advanced/Metastatic Solid Tumors
Lead sponsor: Adagene Inc
Sponsor class: INDUSTRY
First posted: 2020-11-27
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: ADG126, ADG126 in Combination with anti-PD1 antibody, and ADG126 in Combination with ADG106 in Patients with Advanced/Metastatic Solid Tumors .

Detailed description: ADG126 is a novel anti-CTLA-4 fully human IgG1 antibody prodrug that is modified with Adagene Safebody technology to control the activation of anti-CTLA4 activity.ADG106 is a fully human ligand-blocking, agonistic anti-CD137 IgG4 mAb which is expected to enhance the activity of activated T cells. The enhanced antitumor efficacy results observed from the preclinical studies of ADG126 in combination with ADG106 or anti-PD-1 provided further support to explore such combinations in clinical settings for better patient responses.

Eligibility criteria: Inclusion criteria

1. Adults ≥18 years of age.
2. ECOG performance status 0 or 1.
3. Estimated life expectancy of more than 12 weeks .
4. Patients with advanced or metastatic solid tumors, confirmed by histologically or pathologically documented, who have progressed after all standard therapies, or for whom no further standard therapy exists.
5. At least 1 measurable lesion at baseline according to the definition of RECIST v1.1.
6. Adequate organ function.
7. Meets the additional tumor type requirements as specified in Protocol.

Exclusion Criteria:

1. Treatment with any investigational drug within washout period.
2. Major trauma or major surgery within 4 weeks prior to first dose of study drug(s)
3. History of significant immune-mediated AE.
4. Central nervous system (CNS) disease involvement.
5. Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC)/bone marrow (BM) transplantation
6. Clinically significant cardiac disease.
7. Evidence of active uncontrolled viral, bacterial, or systemic fungal infection.
8. Patients who received:

   1. A COVID-19 vaccine within 7 days of Cycle 1 Day 1.
   2. Live vaccines or live-attenuated vaccines within 28 days prior to Cycle 1 Day 1.
9. Known active infection of HBV/BCV/HIV.
10. Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (\>10 mg/day prednisone or equivalent).
11. Second primary malignancy not in remission for greater than 3 years.
12. History(within the last 5 years) or risk of autoimmune disease.
13. Pregnant or breastfeeding females.
14. Childbearing potential who does not agree to the use of contraception during the treatment period.

Primary outcomes:
measure: Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors
timeFrame: From first dose of ADG126 (Week 1 Day 1) until 21 days
measure: Number of participants with adverse events as assessed by CTCAE v5.0 ADG126-ADG106 combination regimens
timeFrame: From first dose of ADG126 (Week 1 Day 1) to 90 days post last dose
Secondary outcomes:
measure: Antidrug antibodies (ADAs)
timeFrame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
measure: Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)
timeFrame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
measure: Maximum (peak) plasma concentration (Cmax)
timeFrame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
measure: Time to maximum (peak) plasma concentration (Tmax)
timeFrame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
measure: Trough plasma concentration (Ctrough)
timeFrame: From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Antonio
country: United States
facility: Next oncology
state: Texas
city: Miranda
country: Australia
facility: Southside Cancer Care Centre
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Birtinya
country: Australia
facility: Sunshine Coast University Private Hospital
state: Queensland
city: Malvern
country: Australia
facility: Cabrini Health Limited
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research Pty Ltd
state: Western Australia
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
References: