A Phase I Open-label, Multi-center, Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics and Antitumor Activity of HC010 in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- HC010
- Conditions
- Advanced Solid Tumor
- Sponsor
- HC Biopharma Inc.
- Enrollment
- 122
- Locations
- 1
- Primary Endpoint
- Recommended Dose for Phase II Clinical Studies
- Status
- Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
This clinical trial is a multicenter, open, single-arm, non-randomized, dose-escalation and dose-expansion, phase I clinical study in patients with advanced recurrent or metastatic solid tumors.The goal of this study is to evaluate the safety and tolerability of HC010 monotherapy in patients with advanced solid tumors.
Detailed Description
This clinical trial is a multicenter, open, single-arm, non-randomized, dose-escalation and dose-expansion, phase I clinical study in patients with advanced recurrent or metastatic solid tumors.The goal of this study is to evaluate the safety and tolerability of HC010 monotherapy in patients with advanced solid tumors.Enrollment is for patients with advanced adult solid tumors (including but not limited to non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, cervical cancer, triple-negative breast cancer, gastric cancer/gastroesophageal junction adenocarcinoma, ovarian cancer, pancreatic cancer, bladder cancer, and renal cancer) who have either failed to respond to standard of care or who are unable to receive/do not have access to standard of care.Subjects received HC010 monotherapy by intravenous infusion every two weeks in 1 cycle of 28 days, and were treated until completion of 2 years of study treatment, disease progression, intolerable toxicity, withdrawal of informed consent, loss to follow-up, death, or fulfillment of other criteria for termination of treatment, whichever occurred first. The primary study endpoints were safety and tolerability, maximum tolerated dose (MTD) and/or recommended dose for phase II clinical studies (RP2D); secondary endpoint indicators included pharmacokinetic indicators, efficacy indicators \[objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS)\], immunogenicity indicators such as anti-drug antibody (ADA) and neutralizing antibody (Nab). Exploratory endpoints included the pharmacokinetic (PD) index of HC010, the relationship between peripheral blood T-cell receptor occupancy (RO) and safety and efficacy, as well as the correlation between PD-L1 expression level in tumor tissues and efficacy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntary participation in this clinical trial, understanding and following the research protocol, and voluntarily signing the Informed Consent Form (ICF).
- •Age ≥18 and ≤75, male or female.
- •Participants with histologically or cytologically confirmed diagnosis of advanced solid tumors who have failed standard therapy or for whom no standard therapy is available.
- •Participants must have at least one measurable lesion according to RECIST Version1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
- •Hepatocellular carcinoma patients with Child-Pugh score ≤ 7
- •Expected survival time is at least 3 months
- •Adequate organ function: neutrophil count≥1.5×109/L,platelet count ≥100×109/L,hemoglobin≥90g/L,alanine aminotransferase and aspartate aminotransferase ≤2.5×upper limit of normal (ULN); patients with hepatocellular carcinoma or concomitant hepatic metastases ≤5.0×ULN, total bilirubin ≤1.5×ULN, renal function and cardiopulmonary function are basically normal.
- •Subjects should provide, whenever possible, freshly obtained or archived tumor tissue sample prior to study treatment that can be used for biomarker analysis
- •Participants of childbearing potential (males and females) must agree to effective contraception for at least 90 days from the time of signing the informed consent form to the time of the last dose; females of childbearing potential must have a negative blood pregnancy test within 7 days prior to the first dose of the HC010
Exclusion Criteria
- •Receipt of any interventional clinical trial treatment or other systemic chemotherapy, radiotherapy, etc. within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of the HC010; Receipt of herbal or proprietary Chinese medicine with an anti-tumor indication within 2 weeks prior to the first dose of HC010;
- •Underwent surgery, experienced severe trauma, etc,within 4 weeks prior to the first administration of HC010 ;
- •Receipt of systemic glucocorticoids (prednisone \>10 mg/day or equivalent doses of similar drugs) or other immunosuppressive agents within 2 weeks prior to the first dose of HC010;
- •Receipt of immunomodulatory drugs within 2 weeks prior to the first dose of HC010;
- •Receipt of live attenuated vaccination within 4 weeks prior to the first dose of HC010;
- •Patients who have received biomolecule therapy for anti-programmed death receptor 1 (PD-1)/programmed death ligand (PD-L1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), and anti-vascular endothelial growth factor (VEGF) targets in prior antitumor therapy;
- •Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade≤1;
- •History of immune-related adverse event (irAE) leading to permanent discontinuation from prior immunotherapy ,or grade ≥3 toxicity related to anti-angiogenic therapy from prior anti-angiogenic therapy；
- •Previous allogeneic hematopoietic stem cell transplantation or organ transplantation；
- •Patients with known active brain metastases, or the presence of meningeal metastases, spinal cord compression, or molluscum contagiosum disease；
Arms & Interventions
dose-escalation phase
HC010 0.15mg/kg to 20mg/kg Q2w/28d intravenous infusion
Intervention: HC010
dose expansion phase
Fixed dose of HC010 Q2w/28d intravenous infusion
Intervention: HC010
Outcomes
Primary Outcomes
Recommended Dose for Phase II Clinical Studies
Time Frame: 2 years
Recommended Dose for Phase II Clinical Studies
Incidence of dose-limiting toxicity
Time Frame: 28 days
Incidence of dose-limiting toxicity
Adverse events
Time Frame: 2 years
Adverse events
serious adverse events
Time Frame: 2 years
serious adverse events
Maximum Tolerated Dose
Time Frame: 2 years
Maximum Tolerated Dose
Secondary Outcomes
- pharmacokinetics:Cmax(2 years)
- Objective response rate(2 years)
- duration of response(2 years)
- pharmacokinetics:Vd(2 years)
- overall survival(2 years)
- pharmacokinetics:AUC0-last(2 years)
- pharmacokinetics:tmax(2 years)
- progression-free survival(2 years)
- Disease control rate(2 years)