Clinical trial NCT04501276: A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients
Official title: A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study of ADG116, ADG116 Combined With Toripalimab (Anti-PD-1 Antibody), ADG116 Combined With ADG106 (Anti-CD137 Antibody) in Patients With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Keywords: Advanced/Metastatic Solid Tumors
Lead sponsor: Adagene Inc
Sponsor class: INDUSTRY
First posted: 2020-08-06
Enrollment: 72
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: This is a Phase 1, open-label, dose escalation study in patients with advanced/metastatic solid tumors. Study drug, ADG116, is an anti -CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4. ADG106, a fully human ligand-blocking agonistic anti-CD137 IgG4 mAb, is expected to enhance the activity of activated T cells. The enhanced antitumor efficacy results observed from the preclinical studies of ADG116 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:

Patients must meet all of the following inclusion criteria to be eligible for participation in this study:

1. ≥ 18 years of age at the time of informed consent.
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
3. Patients with advanced or metastatic solid tumors, who have progressed after all standard therapies, or for whom no further standard therapy exists.
4. At least 1 measurable lesion at baseline according to the definition of RECIST v1.1.
5. Adequate organ function.

Exclusion Criteria:

• Patients who meet any of the following criteria cannot be enrolled:

1. Pregnant or breastfeeding females.
2. Childbearing potential who does not agree to the use of contraception during the treatment period..
3. Treatment with any investigational drug within washout period.
4. Grade ≥ 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior immunotherapy.
5. Central nervous system disease involvement
6. History or risk of autoimmune disease.
7. History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or any ingredients contained in the ADG116 drug formulation.
8. Patients requiring systemic treatment with corticosteroids
9. Patients receiving granulocyte colony stimulating factor (G-CSF), within 14 days prior to the first dose of the study drug.
10. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic obstructive pulmonary disease (COPD).
11. Major surgery within 4 weeks prior to the first dose of the study drug.
12. Has had an allogeneic tissue/solid organ transplant.

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 ADG116 (Week 1 Day 1) until 21 days
measure: Number of participants with adverse events as assessed by CTCAE v5.0
timeFrame: From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
Secondary outcomes:
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)
measure: Incidence of ADAs
timeFrame: From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
measure: Preliminary evidence of antitumor activity as characterized by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), duration of stable disease, progression free survival (PFS), and overall survival (OS).
timeFrame: From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research
city: Malvern
country: Australia
facility: Cabrini Hospital
city: Sydney
country: Australia
facility: Macquarie University
Study officials:
References:
citation: Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
citation: Melero I, Hervas-Stubbs S, Glennie M, Pardoll DM, Chen L. Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer. 2007 Feb;7(2):95-106. doi: 10.1038/nrc2051.
citation: Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012 Sep;23 Suppl 8(Suppl 8):viii6-9. doi: 10.1093/annonc/mds256.