ADG126 in Combination With Pembrolizumab in Patients With Advanced/Metastatic Solid Tumors

• Status: Not yet recruiting
• Trial end date: 2025-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 1b/2, open-label, dose escalation study to evaluate the safety, tolerability, PK, and immunogenicity of an ADG126-pembrolizumab combination regimen in patients with advanced/metastatic solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Adagene Inc
• Collaborator: Merck Sharp & Dohme LLC
• Treatments: Pembrolizumab

Criteria

Inclusion Criteria:

1. ≥ 18 years of age at the time of informed consent.

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

3. Patients with advanced or metastatic solid tumors, histologically or pathologically confirmed, 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.

4. Patients should have at least 1 measurable lesion at baseline according to the definition of RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

5. Adequate hematologic function, defined by the following:

1. Absolute neutrophil count (ANC) ≥ 1.5 ×109/L, without the use of granulocyte colony stimulating factor such as filgrastim within 2 weeks prior to study treatment.

2. Platelet count ≥ 75 × 109/L without transfusion within 2 weeks (≤ 14 days) prior to study treatment.

3. Hemoglobin ≥ 8 g/dL without transfusion or erythropoietin within 2 weeks (≤ 14 days) prior to study treatment.

6. AST and ALT ≤ 2.5 × upper limit of normal (ULN), and total bilirubin ≤ 1.5 × ULN. Exception: Patients who have serum bilirubin increases due to documented underlying Gilbert's Syndrome or familial benign unconjugated hyperbilirubinemia may be enrolled. Patients with known liver metastases or patients with hepatocellular carcinoma may be enrolled with AST, ALT and/or total bilirubin ≤ 5 × the ULN

7. Adequate renal function defined by either a creatinine clearance ≥ 45 mL/min (by Cockcroft-Gault formula) or SCr ≤ 1.5 × ULN.

8. Coagulation tests, defined by the following:

1. aPTT ≤ 1.5 × ULN.

2. INR ≤ 1.5 × ULN. Exception: INR ≤ 3 × ULN is acceptable for patients on Warfarin anticoagulation.

9. Previous AEs have been improved to baseline or Grade ≤ 1 NCI CTCAE v5.0 (except for patients with alopecia). Participants with Grade ≤ 2 neuropathy may be eligible. Participants with endocrine-related AEs Grade ≤ 2 requiring treatment or hormone replacement may be eligible.

Exclusion Criteria:

1. Pregnant or breastfeeding females.

2. Females of childbearing potential and males whose partners are of childbearing potential who do not agree to the use of 2 forms of highly effective contraception during the treatment period and for 6 months after the last dose of study drug.

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

4. Grade ≥ 3 immune-related AEs (irAEs) or irAE that led to discontinuation of prior immunotherapy.

5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.

6. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

7. Active viral (any etiology) hepatitis patients are excluded. Hepatitis B virus (HBV) carriers are ineligible. Cured Hepatitis C virus (HCV) (negative HCV RNA test) patients may be enrolled after consulting with the Medical Monitor.

8. Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled diabetes as evidenced by Screening (baseline) HgbA-1c ≥ 8, asthma, COPD, or other conditions that pose a risk to the patient participating on study.

9. Has a known history of HIV infection.

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

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

12. Has had an allogeneic tissue/solid organ transplant.

13. Clinically significant cardiac conditions, including myocardial infarction within the last 6 months, uncontrolled angina, viral myocarditis, pericarditis, cerebrovascular accident, or other acute uncontrolled heart disease < 3 months prior to the first dose of the study drug; left ventricular ejection fraction (LVEF) < 50%, New York Heart Association (NYHA) Class III or IV congestive heart failure, or uncontrolled hypertension.

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

15. Has received a COVID-19 vaccine within 7 days prior to the first dose of study treatment. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed.

16. A positive COVID-19 test within 14 days of Cycle 1 Day 1.

17. Any other disease or clinically significant abnormality in laboratory parameters, including serious medical or psychiatric illness/condition, which in the judgment of the Investigator might compromise the safety of the patient or integrity of the study, interfere with the patient participation in the trial or compromise the trial objectives.