A Phase Ⅰ, Multi-center, Open-label, Single-arm, Dose Escalation, First-in-human Clinical Study of HY-0102 Monotherapy in Patients With Locally Advanced/Metastatic Solid Tumours
Overview
- Phase
- Phase 1
- Intervention
- HY-0102
- Conditions
- Locally Advanced/Metastatic Solid Tumors
- Sponsor
- Shanghai HyaMab Biotech Co.,Ltd.
- Enrollment
- 17
- Locations
- 3
- Primary Endpoint
- Incidence of Treatment-emergent adverse event (TEAEs) and serious adverse events (SAEs).
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a Phase I, first-in-human trial to evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of HY-0102 administered intravenously (IV) once every two weeks in adult patients with locally advanced/metastatic malignant solid tumors.
Detailed Description
This is a Phase I, first-in-human trial to evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of HY-0102 administered intravenously (IV) once every two weeks in adult patients with locally advanced/metastatic malignant solid tumors (head and neck, liver, colorectal and lung cancers, etc). Six dosing cohorts are planned with the dose of 0.03, 0.3, 1, 2, 4 and 10 mg/kg. The first two dose levels (0.03 and 0.3 mg/kg) will each enroll one patient using an accelerated escalation design that will convert to a 3+3 design upon the occurrence of one treatment-related Grade 2 toxicity occurring in the safety evaluation window following the first dose of treatment. After the initial two cohorts are completed, the study will use a standard 3+3 dose escalation design. The number of enrolled patients is estimated to be up to 32. The dose limiting toxicity evaluation period will be the first 28 days (Cycle 1) and subsequent cycles will be 4 weeks in duration. Patients will receive the investigational drug on Day 1 of cycle 1 followed by 28 days of observation. HY-0102 will be administered IV once every two weeks for Cycle 2 and beyond.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥ 18 years
- •Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures.
- •Histologically or cytologically confirmed incurable, unresectable, locally advanced or metastatic cancer that is refractory to standard therapies.
- •Prior Therapy
- •Have progressed on or are intolerant to all standard therapies
- •Have no available therapies known to confer clinical benefit
- •Measurable or evaluable disease per RECIST v1.1 Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam.
- •ECOG performance status 0 or 1; Life expectancy ≥ 3 months.
- •Adequate hepatic function as evidenced by meeting all the following requirements:
- •Total bilirubin ≤ 1.5 ×within institutional upper limit of normal (ULN); or ≤ 2.5 × institutional ULN for patients who have serum bilirubin increases due to underlying Gilbert's Syndrome or familial benign.
Exclusion Criteria
- •Symptomatic central nervous system metastases. Patients with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS-directed therapy, and are on a stable or decreasing dose of corticosteroids are eligible for study entry.
- •Uncontrolled hypertension (systolic blood pressure \>150 mmHg and diastolic blood pressure \>90 mmHg), a history of hypertension crisis, or a history of hypertensive encephalopathy.
- •Severe cardiovascular disease, including CVA, TIA, myocardial infarction, or unstable angina within 6 months of study entry; NYHA class III or IV heart failure within 6 months of study entry; Uncontrolled arrhythmia within 6 months of study entry.
- •QTc \> 450 ms at baseline; no concomitant medications that would prolong the QT interval; no family history of long QT syndrome \[consider QTc \< 480 rather than 450\]
- •Concurrent malignancy within 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active surveillance, prostate cancer that has undergone definitive treatment, ductal carcinoma in situ of the breast, or \< T1 urothelial carcinoma.
- •Active infection requiring intravenous therapy within 2 weeks prior to entry.
- •Active HIV, hepatitis B or hepatitis C virus. or
- •Patients infected with the HIV virus will be eligible if their CD4 count is \> 350 cells/mm3 and the patient is on anti-retroviral therapy with an HIV viral load that is below the level of detection.
- •Active hepatitis B or C. HBV carriers without active disease (HBV DNA titer \< 1000 cps/mL or 200 IU/mL), or cured Hepatitis C (negative HCV RNA test) may be enrolled. For patients with hepatocellular carcinoma, patient with chronic infections with hepatitis C virus (treated or untreated); and patients with hepatitis B virus who were treated with antiviral therapy and who had a HBV viral load less than 200 IU/mL may also be enrolled.
- •Active tuberculosis
Arms & Interventions
Dose Escalation
Cohort 1: 0.03 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Accelerated dose escalation: One patient will be enrolled. Cohort 2: 0.3 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Accelerated dose escalation: One patient will be enrolled. Cohort 3: 1 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Standard 3+3 Dose escalation: Three patients will be enrolled for each dose cohort. Cohort 4: 2 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Standard 3+3 Dose escalation: Three patients will be enrolled for each dose cohort. Cohort 5: 4 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Standard 3+3 Dose escalation: Three patients will be enrolled for each dose cohort. Cohort 6: 10 mg/kg Q2W HY-0102 ivgtt Duration: 26w DLT observation period: 28 days Standard 3+3 Dose escalation: Three patients will be enrolled for each dose cohort.
Intervention: HY-0102
Outcomes
Primary Outcomes
Incidence of Treatment-emergent adverse event (TEAEs) and serious adverse events (SAEs).
Time Frame: From the start of treatment until up to 90 days after the last dose of study drug
To assess by the occurrence of Treatment-emergent adverse event (TEAEs) and serious adverse events (SAEs)
Number of participants with changes in Clinically Significant Vital Sign from baseline
Time Frame: From the start of treatment until up to 30(±7) days after the last dose of study drug
To assess safety of HY-0102
Number of patients with changes in electrocariogram (ECG) from baseline
Time Frame: From the start of treatment until up to 30(±7) days after the last dose of study drug
To assess safety of HY-0102
Occurrence of Drug Limited Toxicities (DLTs)
Time Frame: From Time of First dose through DLT observation period, 28 days
To assess by the occurrence of Drug Limited Toxicities (DLTs)
Number of patients with changes in laboratory parameters from baseline
Time Frame: From the start of treatment until up to 30(±7) days after the last dose of study drug
To assess safety of HY-0102
Number of participants with changes in left ventricular ejection fraction (LVEF) from baseline
Time Frame: From the start of treatment until up to 30(±7) days after the last dose of study drug
To assess safety of HY-0102
Secondary Outcomes
- Ctrough (Trough observed serum concentration) of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- Cmax (Maximum observed serum concentration) of HY-0102(From first dose through 30days(±7) days after the last dose of study medication)
- Tmax (Time of maximum observed serum concentration) of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- DCR (confirmed response or stable disease lasting for at least 6 months)(FU period/EOS visits every 3 months (± 14 days) after the EOT visit for 6 months)
- T1/2 (Elimination half life) of HY-0102(From first dose through 30 days (+/- 7 days) after the last dose of study medication)
- Vss (Volume of distribution at steady state) of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- AUC(0-T) [Area under the concentration-time curve from time zero to the last quantifiable concentration] of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- AUC(tau) [Area under the concentration-time curve in one dosing interval] of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- AUC(inf) [Area under the concentration-time curve from time zero to infinity and the extrapolated area] of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- Anti-drug Antibody (ADA) and Neutralizing Antibody (NAb)(From first dose through 30(±7) days after the last dose of study medication)
- ORR (confirmed complete or partial response)(FU period/EOS visits every 3 months (± 14 days) after the EOT visit for 6 months)
- CL(Total body clearance) of HY-0102(From first dose through 30(±7) days after the last dose of study medication)
- Duration of Response (DoR)(FU period/EOS visits every 3 months (± 14 days) after the EOT visit for 6 months)
- Progression Free Survival (PFS)(FU period/EOS visits every 3 months (± 14 days) after the EOT visit for 6 months)
- PD parameters: receptor occupancy (RO) of HY-0102(From first dose through 30(±7) days after the last dose of study medication)