Phase 1 Study of HLX10, a Monoclonal Antibody Targeting Programmed Death-1 (PD-1) in Patients With Advanced Solid Tumors

• Status: Unknown status
• Trial end date: 2020-08-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of humanized anti-PD-1 monoclonal antibody, HLX10, in patients with advanced or metastatic tumors refractory to standard therapy. This study will also evaluate the pharmacokinetics, pharmacodynamics, immunogenicity and anti-tumor effect of HLX10 and explore the potential prognostic and predictive biomarkers.

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

Details

• Lead Sponsor: Henlix, Inc
• Treatments: Antibodies; Antibodies, Monoclonal; Immunoglobulins

Criteria

Inclusion Criteria:

1. Histologically-confirmed, unidimensionally-measurable and/or evaluable carcinoma which has failed standard therapy or for which no standard therapy is available.

2. ECOG performance status score of ≤ 2 at study entry.

3. Able to provide written informed consent.

4. A life expectancy longer than three months as determined by the investigator.

5. Adequate hematologic functions, as defined by: absolute neutrophil counts ≥ 1500/mm3; a hemoglobin level ≥ 10 gm/dL; a platelet count ≥ 100,000/mm3.

6. Adequate hepatic function defined by: a total bilirubin level ≤ 1.5x of upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 x of ULN or ≤ 5x of ULN in known hepatic metastases or with primary hepatocellular carcinoma.

7. Adequate renal function, as defined by the creatinine clearance rate ≥ 50 mL/minute by Cockcroft-Gault formula.

8. Adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥ 50%.

9. Use of effective contraceptive measures if procreative potential exists.

10. At least 28 days from prior major surgery, prior cytotoxic chemotherapy, or prior therapy with investigational agents (or medical device) or local radiotherapy and at least 42 days from the last infusion of immune check point inhibitors (including anti-PD-1 or anti-PD-L1) before the first infusion of investigational product.

11. For patients with hepatocellular carcinoma, their Child-Pugh score has to be A.

12. Able to be followed up as required by the study protocol.

Exclusion Criteria:

1. Patients who still have persistent ≥ grade 2 toxicities from prior therapies.

2. Concurrent unstable or uncontrolled medical conditions. Either of the followings:

• Active systemic infections;

• Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥100 mmHg), or poor compliance with anti-hypertensive agents;

• Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (class III or IV of New York Heart Association [NYHA]) or acute myocardial infarction within 6 months;

• Uncontrolled diabetes or poor compliance with hypoglycemic agents;

• The presence of chronically unhealed wound or ulcers;

• Other chronic diseases, which, in the opinion of the investigator, could compromise safety of the patient or the integrity of study.

3. Newly-diagnosed or symptomatic brain metastases (patients with a history of brain metastases must have received definitive surgery or radiotherapy, be clinically stable, and not taking steroids for brain edema). Anticonvulsants are allowed.

4. Any concurrent malignancy other than basal cell carcinoma or carcinoma in situ of the cervix. (Patients with a previous malignancy but without evidence of disease for ≥ 3 years are allowed to participate).

5. Pregnancy (confirmed by serum beta human chorionic gonadotropin [ßHCG]) or breast-feeding.

6. Known history of human immunodeficiency virus infection (HIV).

7. Patient who has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroid (more than 10 mg per day) or immunosuppressive agents.

8. Patient who has active hepatitis B (HBsAg reactive) or hepatitis C (defined anti-HCV reactive)

9. Patient who has a history of interstitial lung disease

10. The patient is the investigator, sub-investigator or any one directly involved in the conduct of the study.

11. Patient has a history or current evidence of any condition or disease that could confound the results of the study, or is not the best interest of the patient to participate, in the opinion of Investigator.