A Phase 1b/2 Study of ADG116, ADG116 Combined With Anti-PD-1 Antibody or Anti-CD137 Antibody in Solid Tumors Patients

Advanced/Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04501276
• Other study ID #: ADG116-1003
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 23, 2020
• Est. completion date: August 15, 2024

Study information

• Verified date: January 2024
• Source: Adagene Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: August 15, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced/Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ADG116
For monotherapy ADG116 (Part A), ADG116 will be administered IV over 60 90 minutes until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.
• ADG106
For the ADG116-ADG106 combination regimen, ADG116 and ADG106 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.
• anti PD1 drug
For the ADG116-anti PD1 combination regimen, ADG116 and anti PD1 will be administered until disease progression, intolerable toxicities, or withdrawal of consent, or up to 2 years.

Locations

Country	Name	City	State
Australia	Ashford Cancer Centre Research	Kurralta Park
Australia	Cabrini Hospital	Malvern
Australia	Macquarie University	Sydney
United States	Next Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Adagene Inc

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors		From first dose of ADG116 (Week 1 Day 1) until 21 days
Primary	Number of participants with adverse events as assessed by CTCAE v5.0		From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
Secondary	Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)		From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
Secondary	Maximum (peak) plasma concentration (Cmax)		From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	Time to maximum (peak) plasma concentration (Tmax)		From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	Trough plasma concentration (Ctrough)		From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	Incidence of ADAs		From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years)
Secondary	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).		From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose