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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A : Dose escalation of ADG116 monotherapy | Experimental |
| |
| Part B : Dose escalation of ADG116 combined with anti PD1 drug | Experimental |
| |
| Part C : Dose escalation of ADG116 combined with ADG106 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ADG116 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | |
| Maximum (peak) plasma concentration (Cmax) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) |
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Inclusion Criteria:
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
Exclusion Criteria:
• Patients who meet any of the following criteria cannot be enrolled:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Next Oncology | San Antonio | Texas | 78229 | United States | ||
| Ashford Cancer Centre Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29442540 | Background | 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. | |
| 17251916 |
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| ADG106 | Drug | 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 | 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. |
|
| Time to maximum (peak) plasma concentration (Tmax) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) |
| Trough plasma concentration (Ctrough) | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) |
| Incidence of ADAs | From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years) |
| 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 |
| Kurralta Park |
| Australia |
| Cabrini Hospital | Malvern | Australia |
| Macquarie University | Sydney | Australia |
| Background |
| 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. |
| 22918931 | Background | 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. |