Clinical trial NCT05394168: A Phase I Clinical Study of HLX53 in Advanced/Metastatic Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HLX53 (an Anti-TIGIT Fc Fusion Protein) in Patients With Advanced/Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced/Metastatic Solid Tumors
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2022-05-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I, first-in-human, open-label clinical study will evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of HLX53 (an anti-TIGIT Fc fusion protein) in patients with advanced/metastatic solid tumors.

Detailed description: This study is an open-label phase I clinical study to evaluate the safety, tolerability , PK/PD and preliminary efficacy of HLX53 in patients with advanced/metastatic solid tumor. 11-30 subjects with advanced or metastatic solid tumors will be enrolled. The accelerated titration and traditional 3 + 3 dose escalation design will be implemented. Subjects will receive intravenous infusion of HLX53 at different doses according to the order of enrollment. There are 5 preset dose groups, namely 30mg/QW, 150mg/QW, 400mg/QW, 1000mg/Q3W and 2000mg/Q3W, administered by intravenous infusion. Observation period of DLT will last for 21 days after the first administration of HLX53. Maximum tolerated dose (MTD) definition: The highest dose level at which no more than 1 of 6 DLT-evaluable subjects developed DLT. At the MTD dose, at least 6 subjects were evaluable for DLT. When the MTD is determined, the MTD is usually used as the RP2D, or the RP2D is determined based on safety, PK/PD/ADA/NAb characteristics, and potential clinical efficacy.

Eligibility criteria: Inclusion Criteria:

* Voluntary participation in clinical studies, full understanding of the trial, and signing of informed consent, willingness to follow and ability to complete the study in accordance with the requirements of the trial protocol.
* histologically or cytologically confirmed advanced/metastatic solid tumors or lymphoma, failure of standard therapy, or no standard therapy.
* Age ≥ 18 years and ≤ 75 years at the time of informed consent.
* Eastern Cooperative Oncology Group (ECOG) score 0 or 1.
* At least one measurable lesion according to RECISTv1.1 or 2014 Lugano (lymphoma) response evaluation criteria.
* Life expectancy of more than three months.
* Adequate hematological function.
* Adequate liver function.
* Adequate renal function
* Adequate cardiac function.
* Male and female subjects of childbearing potential must agree to use at least 1 highly effective method of contraception during the trial and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

* Known history of serious allergy to the components of HLX53 or to any monoclonal antibody.
* Prior treatment with anti-TIGIT or antibody to the relevant target CD155, CD112, or CD113.
* Unresolved toxicity after prior antineoplastic therapy, i.e., not resolved to baseline, Grade 0-1 per NCI-CTCAE 5.0 (except alopecia).
* Coexisting unstable or controlled medical conditions.
* Spinal cord compression with clinical symptoms.
* Prior allogeneic bone marrow transplant or solid organ transplant.
* History of primary immunodeficiency.
* History of eczema or asthma that cannot be controlled by topical corticosteroids.
* History of any second malignancy within 2 years, except for curatively treated early malignancies (carcinoma in situ or stage I tumors) such as non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, ductal carcinoma in situ of the breast, papillary thyroid cancer.
* Vaccination with a live attenuated vaccine within 4 weeks prior to the first dos.e
* Use of immunosuppressive drugs within 2 weeks prior to initial administration.
* Received major surgery, anti-tumor therapy (chemotherapy, radiotherapy, targeted therapy, immunotherapy or biological therapy) within 4 weeks prior to the first dose.
* Known to have active infectious disease such as active HBV, HCV infection.
* History of human immunodeficiency virus (HIV) infection.
* Pregnancy or lactation.

Primary outcomes:
measure: Adverse event
timeFrame: Through study completion, assessed up to 2 years.
measure: Incidence of DLT
timeFrame: Up to 3 weeks.
measure: MTD
timeFrame: Up to 3 weeks
measure: RP2D
timeFrame: Through study completion, assessed up to 2 years.
Secondary outcomes:
measure: Cmax
timeFrame: From baseline to 30 days after the last administration, assessed up to 7 months
measure: Tmax
timeFrame: From baseline to 30 days after the last administration, assessed up to 7 months
measure: t1/2
timeFrame: From baseline to 30 days after the last administration, assessed up to 7 months
measure: TIGIT Receptor Occupancy
timeFrame: From baseline to 30 days after the last administration，assessed up to 7 months
measure: ADA
timeFrame: From baseline to 30 days after the last administration，assessed up to 7 months
measure: Objective response rate (ORR)
timeFrame: Through study completion, assessed up to 2 years.
measure: Progression-free survival (PFS)
timeFrame: From date of the first HLX53 administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years.
measure: Overall survival(OS)
timeFrame: From date of the first HLX53 administration until the date of death from any cause, whichever came first, assessed up to 2 years.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
affiliation: Fudan University
name: Jian Zhang
role: PRINCIPAL_INVESTIGATOR
References: