A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting PD-L1Protein in Patients With Advanced Solid Tumors

NCT03588650 | Completed Phase 1

• 1 other identifier: HLX20-001
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, dose escalation, first-in-human study of HLX20, an anti-PD-L1 monoclonal antibody, in patients with metastatic or recurrent solid tumors who have failed standard therapy.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of HLX20 in solid tumors patients

  The target toxicity rate in this study for the MTD is set at 0.3 ( 30% DLT) identified by an adaptive Bayesian dose-finding design .

  1 year

Secondary Outcomes (10)

• Maximum serum concentration (Cmax) of HLX20.

  1 year

• Minimum serum concentration (Cmin) of HLX20.

  1 year

• Area under serum concentration-time curve within one dosing interval (AUC0-tau) of HLX20.

  1 year

• Terminal elimination half-life (T1/2) of HLX20 in different cohorts

  1 year

• Clearance rate (CL) of HLX20

  1 year

Study Arms (1)

HLX20, in patients with solid tumors

EXPERIMENTAL

Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX20 once every two weeks. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 1, 3, 10 and 20 mg/kg, starting from 1 mg/kg.

Drug: HLX20

Interventions

HLX20 DRUG

a Human Monoclonal Antibody Targeting Programmed Death Ligand-1 (PD-L1) Protein

HLX20, in patients with solid tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females of 18 years of age or older (or per local regulations).
• Have histologically-proven measurable, or evaluable advanced (systemically or locally progressive), or metastatic solid tumors or the locally advanced disease is not amenable to local therapy, who have failed, or are intolerant to standard therapy or for whom no standard therapy is available. (For patients with hepatocellular carcinoma, the diagnosis needs to be supported by dynamic computed tomography \[CT\]/magnetic resonance imaging, if pathological confirmation is not attainable).
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study entry.
• Able to comprehend and provide informed consent.
• A life expectancy longer than 3 months in the opinion of the Investigator.
• Adequate hematologic functions, as defined by: absolute neutrophil counts
• ≥ 1500/mm3; a hemoglobin level ≥ 10 g/dL; a platelet count ≥ 100,000/mm3.
• Adequate hepatic function defined by: a total bilirubin level ≤ 1.5 × of upper limit of normal (ULN); aspartate transaminase and alanine transaminase levels ≤ 2.5 × ULN or ≤ 5 × ULN in known hepatic metastases or with primary hepatocellular carcinoma.
• Adequate renal function, as defined by the creatinine clearance ≥ 50 mL/minute (as calculated by the Cockcroft-Gault formula).
• Adequate cardiac function defined as left ventricular ejection fraction ≥ 50% by cardiac ultrasound or multigated acquisition (MUGA) scan. A recent MUGA scan is acceptable if performed within 8 weeks of the first infusion of IP.
• Females of child-bearing potential must have a negative pregnancy test upon entry into this study and must be willing to use highly effective birth control upon enrollment, during the Treatment Phase and for 180 days following the last dose of study drug. A female is considered of child-bearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
• If male, must be surgically sterile or willing to use highly effective birth control upon enrollment, during the Treatment Phase, and for 180 days following the last dose of study drug.
• History of prior major surgery, prior cytotoxic chemotherapy, or prior therapy with investigational agents, medical device, or local radiotherapy should be at least 28 days prior to Screening and at least 42 days from the last infusion of immune check point inhibitors (including anti-programmed cell death receptor-1 \[PD-1\] or anti-PD-L1) before the first infusion of IP.
• Child-Pugh score of A (patients with hepatocellular carcinoma only).
• Able to be followed up as required by the study protocol.

You may not qualify if:

• Concurrent unstable or uncontrolled medical conditions, including:
• Active systemic infections;
• Poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg), or poor compliance with antihypertensive agents;
• Clinically significant arrhythmia, unstable angina pectoris, congestive heart failure (Class III or IV of New York Heart Association) 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 the study.
• 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 be taking steroids for brain edema). Anticonvulsants are allowed. Patients with history of leptomeningeal disease will be excluded.
• 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).
• Females who are pregnant, lactating, or intend to become pregnant during their participation in this study.
• Known history of human immunodeficiency virus infection.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease, Wegner syndrome) within the past 2 years. Patients with well controlled vitiligo, alopecia, and Grave's disease, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, or psoriasis not requiring systemic treatment (within the past 3 years), or patients with controlled Type 1 diabetes mellitus who are on a stable insulin regimen are not excluded.
• Current or prior use of immunosuppressive medication within 14 days before the first dose. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids or local steroid injections (eg, intra-articular injection), OR
• systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent, OR

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

Study Sites (6)

Kinghorn cancer centre

Darlinghurst, New South Wales, 2010, Australia

Location

Macquarie University

Darlinghurst, New South Wales, 2109, Australia

Location

Sunshine Coast University Hospital

Brisbane, Queensland, 4000, Australia

Location

Gold Coast Hospital

Southport, Queensland, 4215, Australia

Location

CMAX Clinical research

Adelaide, South Australia, 5000, Australia

Location

Cabrini Hospital

Melbourne, Victoria, 3144, Australia

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2018
• First Posted: July 17, 2018
• Study Start: August 7, 2018
• Primary Completion: June 28, 2021
• Study Completion: June 28, 2021
• Last Updated: June 3, 2022

Record last verified: 2022-06

Locations

AU (6)