ADG126, ADG126 in Combination With Anti PD1 Antibody, and ADG126 in Combination With ADG106 in Advanced/Metastatic Solid Tumors

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

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

Study Overview

• Status: Completed
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Biological: ADG126 Mono; Biological: ADG126-anti PD1; Biological: ADG126-ADG106

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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Miranda, New South Wales, Australia, 2228
      • Southside Cancer Care Centre
    • Sydney, New South Wales, Australia
      • Macquarie University Hospital
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Sunshine Coast University Private Hospital
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Cabrini Health Limited
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • One Clinical Research Pty Ltd
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
  • Texas
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADG126 mono dose escalation; ADG126 monotherapy dose escalation will be traditional 3+3 cohort design.	Biological: ADG126 Mono; ADG126 will be administered as an IV infusion over 30-60 minutes ± 15 minutes.
Experimental: ADG126 mono dose expansion; Monotherapy dose expansion is designed to evaluate the preliminary antitumor activity of ADG126 at RP2D or the doses approved by the SRC.	Biological: ADG126 Mono; ADG126 will be administered as an IV infusion over 30-60 minutes ± 15 minutes.
Experimental: ADG126-anti PD1 drug dose escalation; Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC.	Biological: ADG126-anti PD1; ADG126-toripalimab combination regimen will receive of toripalimab 15 to 30 minutes after the end of the ADG126 infusion
Experimental: ADG126-anti PD1 drug dose expansion; Combination therapy expansion will commence at RP2D or the dose approved by the SRC.	Biological: ADG126-anti PD1; ADG126-toripalimab combination regimen will receive of toripalimab 15 to 30 minutes after the end of the ADG126 infusion
Experimental: ADG126-ADG106 dose escalation; Combination therapy will commence at a dose level lower than the cleared dose from the monotherapy dose escalation arms and approved by the SRC.	Biological: ADG126-ADG106; ADG126-ADG106 combination regimen will be receive of ADG106 15 to 30 minutes after the end of the ADG126 infusion
Experimental: ADG126-ADG106 dose expansion; Combination therapy expansion will commence at RP2D or the dose approved by the SRC.	Biological: ADG126-ADG106; ADG126-ADG106 combination regimen will be receive of ADG106 15 to 30 minutes after the end of the ADG126 infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants experiencing dose-limiting toxicities escalating dose levels in adults with advanced / metastatic solid tumors	From first dose of ADG126 (Week 1 Day 1) until 21 days
Number of participants with adverse events as assessed by CTCAE v5.0 ADG126-ADG106 combination regimens	From first dose of ADG126 (Week 1 Day 1) to 90 days post last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Antidrug antibodies (ADAs)	From first dose (Cycle 1 Day 1, ) until the last dose (up to 2 years)
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)
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)

Collaborators and Investigators

• Sponsor: Adagene Inc
• Investigators: Principal Investigator: Paul De Souza, Professor, Southside Hospital; Principal Investigator: Gary Richardson, Professor, Cabrini Private Hospital; Principal Investigator: Michelle Morris, Professor, Sunshine Coast University Private Hospital; Principal Investigator: Anthony Tolcher, Professor, NEXT Oncology

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): January 29, 2024
• Study Completion (Actual): May 17, 2024

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Advanced/Metastatic Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ADG126-1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No