A Phase Ⅰ, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of DN1508052-01 as a Single Agent When Administered Subcutaneously to Adult Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Solid Tumors
- Sponsor
- Shanghai De Novo Pharmatech Co., Ltd.
- Enrollment
- 19
- Locations
- 3
- Primary Endpoint
- the maximum tolerated dose (MTD)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase I, open-label, multicenter study in adult patients with advanced solid tumors that have progressed despite standard therapy or for which no standard therapy exists. DN1508052-01 will be administered subcutaneously on Day 1, Day 8 and Day 15 in 28-day cycles. Other dose regimens may be explored based on the analysis of emerging PK, pharmacodynamics (PD) and safety data. This study is designed to determine the MTD, RP2D and investigate the safety, tolerability, PK, biomarkers, HPV status and ISR in DN1508052-01-treated patients.
Detailed Description
Study Population is adult patients (≥18 years) with histologically or cytologically confirmed, unresectable advanced solid tumors that have progressed despite standard therapy or for which no standard therapy exists.The selected starting dose, 0.01 mg/m2 of DN1508052-01, SC, on Day 1, Day 8 and Day 15 of each cycle.The starting dose will proceed with one patient. The next dose 0.1 mg/m2 will be explored if safety data permit in that there is no instance of a ≥ Common Terminology Criteria for Adverse Event (CTCAE v5.0) Grade 2 AE that is at least possibly related to the study intervention.then Dose escalation will then proceed following the 3+3 cohorts design.Dose escalation will continue until MTD or RP2D is reached, or the dose escalation will be terminated at the discretion of Investigators and Sponsor (or its designee) based on the analyses of emerging PK, PD, safety and efficacy data.The Primary objective is to determine the maximum tolerated dose (MTD) and recommended phase Ⅱ dose (RP2D) and assess dose-limiting toxicity (DLT) of DN1508052-01 as a single agent when administered subcutaneously to adult patients with advanced solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 years or older;
- •Patients with histologically or cytologically confirmed, unresectable advanced solid tumors that have progressed despite standard therapy or for which no standard therapy exists;
- •Patients must have at least one measurable lesion as defined by RECIST v1.1;
- •ECOG performance score 0 or 1;
- •Life expectancy ≥ 3 months;
- •Patients who have sufficient Baseline organ function and whose laboratory data meet the following criteria at enrollment:
- •Absolute neutrophil count （ANC）≥1.5 × 109/L;
- •Platelets ≥100 × 109/L;
- •Hemoglobin ≥90g/dL;
- •Liver function:
Exclusion Criteria
- •Patients with symptomatic central nervous system (CNS) metastases or carcinomatous meningitis; Note: Patients with treated CNS metastases may participate in this trial if the patient has completed radiotherapy or surgery for CNS metastases \>2 weeks prior to study entry and if the patient is neurologically stable ≥ 2 weeks (no new neurologic deficits from brain metastasis on Screening clinical examination, no new findings on CNS imaging, and no corticosteroids being used).
- •Medical Conditions
- •Patients who have a history of another primary malignancy, with the exception of locally excised non-melanoma skin cancer and carcinoma in situ of uterine cervix. A patient who has had no evidence of disease from another primary cancer for 3 or more years is allowed to participate in the study;
- •Patients who have a known history of active hepatitis C or chronic hepatitis B ("active hepatitis" defined as HCV RNA level ≥ 103 copies/mL for hepatitis C or HBV DNA level ≥ 104 copies/mL for hepatitis B at Screening);
- •Patients who have a known diagnosis of human immunodeficiency virus (HIV);
- •Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator and Sponsor, could affect the patient's participation in the study such as:
- •Uncontrolled diabetes mellitus, HbA1c≥8%;
- •Malignant illnesses that are uncontrolled or whose control may be jeopardized by treatment with this study treatment;
- •Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C (see appendix 8.6);
- •Autoimmune disorders with systemic therapy;
Outcomes
Primary Outcomes
the maximum tolerated dose (MTD)
Time Frame: 28 days
MTD is the highest dose of DN1508052-01 in subjects with DLT less than 33.3% during the DLT observation in the dose escalation
Secondary Outcomes
- Efficacy Assessments(Up to 24 months)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](Up to 24 months)
- Time to peak (Tmax) of plasma concentration(Up to 2 months)
- Maximum plasma concentration (Cmax)(Up to 2 months)
- Halflife (T1/2)(Up to 2 months)
- Clearance/ bioavailability (CL/F)(Up to 2 months)
- Area under curve (AUC)(Up to 2 months)