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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04501276




Registration number
NCT04501276
Ethics application status
Date submitted
29/07/2020
Date registered
6/08/2020
Date last updated
19/10/2020

Titles & IDs
Public title
ADG116 in Patients With Advanced/Metastatic Solid Tumors
Scientific title
A Phase 1, Open-Label, Dose Escalation Study of ADG116 in Patients With Advanced/Metastatic Solid Tumors
Secondary ID [1] 0 0
ADG116-1003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced/Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ADG116

Experimental: ADG116 Dose Escalation Level 1 -

Experimental: ADG116 Dose Escalation Level 2 -

Experimental: ADG116 Dose Escalation Level 3 -

Experimental: ADG116 Dose Escalation Level 4 -

Experimental: ADG116 Dose Escalation Level 5 -

Experimental: ADG116 Dose Escalation Level 6 -

Experimental: ADG116 Dose Escalation Level 7 -

Experimental: ADG116 Dose Escalation Level 8 -

Experimental: ADG116 Dose Escalation Level 9 -


Treatment: Drugs: ADG116
ADG116 will be administered IV over 60-90 minutes with planned doses every three weeks for the first 4 cycles. If no intolerable toxicities occur during the first consecutive four treatment cycles, administration of ADG116 may continue every 12 weeks for a total duration of up to 2 years per agreement with the Investigator and the Sponsor.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors
Timepoint [1] 0 0
From first dose of ADG116 (Week 1 Day 1) until 21 days
Primary outcome [2] 0 0
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Timepoint [2] 0 0
From first dose of ADG116 (Week 1 Day 1) to 28 days post last dose
Secondary outcome [1] 0 0
Area under the time concentration curve (AUC) from time zero to infinity (AUC0-inf)
Timepoint [1] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until the last dose (up to 2 years)
Secondary outcome [2] 0 0
Maximum (peak) plasma concentration (Cmax)
Timepoint [2] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until the last dose (up to 2 years)
Secondary outcome [3] 0 0
Time to maximum (peak) plasma concentration (Tmax)
Timepoint [3] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until the last dose (up to 2 years)
Secondary outcome [4] 0 0
Trough plasma concentration (Ctrough)
Timepoint [4] 0 0
From first dose (Cycle 1 Day 1, each cycle is 21 days) until the last dose (up to 2 years)

Eligibility
Key inclusion criteria
- =18 years of age at the time of informed consent.

- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no
deterioration over the previous 2 weeks.

- Patients with advanced or metastatic solid tumors, confirmed by histopathology, who
have progressed after all standard therapies, or for whom no further standard therapy
exists. Patients who have declined standard therapy or have no access to standard
therapy may be enrolled and the reasons for lack of access need to be documented.

- Patients who are refractory or relapsed to prior anti-CTLA4 checkpoint inhibitors or
anti Programmed cell death protein 1 (PD 1) will also be recruited if they meet all
eligibility criteria.

- Adequate hematologic function

- Adequate renal function

- Previous antitumor therapy (including endocrine, chemoradiotherapy/ radiotherapy,
targeted therapy, or immunotherapy) that has ended at least 4 weeks prior to
administration of ADG116.

- Previous adverse events have been improved to baseline or = Grade 1 NCI CTCAE v5.0
(except for patients with alopecia).
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or breastfeeding females.

- Treatment with any investigational drug within 4 weeks prior to the first dose of
study drug.

- Grade = 3 immune-related AEs (irAEs) or irAE that lead to discontinuation of prior
immunotherapy.

- Patients with active autoimmune disease or a documented medical history of autoimmune
disease.

- Patients requiring systemic treatment with corticosteroids or other immunosuppressive
medications within 21 days before the planned first dose of study drug.

- Active viral (any etiology) hepatitis patient are excluded.

- Known human immunodeficiency virus (HIV) positive status.

- Patients with any type of primary immunodeficiency or autoimmune disorder requiring
treatment.

- Major surgery within 4 weeks prior to the first dose of the study drug.

- Clinically significant cardiac conditions.

- Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose of
study drug.

- Any known, documented, or suspected history of illicit substance abuse.

- Any other disease or clinically significant abnormality in laboratory parameters.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Adagene Inc
Address
Country

Ethics approval
Ethics application status

Summary
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. ADG 116 administered intravenously (IV) over a period of
60-90 minutes. The study is planned to treat up to 60 patients.
Trial website
https://clinicaltrials.gov/show/NCT04501276
Trial related presentations / publications
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.
Chae YK, Arya A, Iams W, Cruz MR, Chandra S, Choi J, Giles F. Current landscape and future of dual anti-CTLA4 and PD-1/PD-L1 blockade immunotherapy in cancer; lessons learned from clinical trials with melanoma and non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018 May 16;6(1):39. doi: 10.1186/s40425-018-0349-3. Review.
Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. doi: 10.1200/JCO.2011.38.4032. Epub 2012 Apr 30. Erratum in: J Clin Oncol. 2012 Oct 10;30(29):3654.
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. Review.
Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. doi: 10.1093/annonc/mds213. Epub 2012 Aug 2.
Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012 Sep;23 Suppl 8:viii6-9. doi: 10.1093/annonc/mds256. Review.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kristine She
Address 0 0
Country 0 0
Phone 0 0
4088389296
Fax 0 0
Email 0 0
kristine_she@adagene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04501276