A Study to Evaluate the Safety, Tolerability of DN1508052-01 in Advanced Solid Tumors

NCT03934359 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: DN1508052-01-101
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• the maximum tolerated dose (MTD)

  MTD is the highest dose of DN1508052-01 in subjects with DLT less than 33.3% during the DLT observation in the dose escalation

  28 days

Secondary Outcomes (7)

• 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

Interventions

DN1508052-01 DRUG

DN1508052-01 will be administered subcutaneously on Day 1, Day 8 and Day 15 of each cycle.

Eligibility Criteria

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

You may qualify if:

• 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:
• Serum bilirubin ≤1.5 × upper limit of normal (ULN) or ≤ 3×ULN in any subject with Gilbert's Syndrome; Aspartate aminotransferase（AST） and alanine aminotransferase（ALT） ≤2.5 × ULN without liver metastases, or ≤5 × ULN if the patient has documented liver metastases;
• International normalization ratio ≤1.2 if the patient is not on anticoagulants, or ≤3 if the patient is on anticoagulants;
• Serum creatinine ≤1.5 mg/dL, or estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2;
• Women of childbearing potential must have a negative serum pregnancy test prior to study entry, and agree to use adequate contraception from study entry through at least 1 month after the last dose of study drug. A female patient of nonchildbearing potential will have had at least 12 continuous months of natural (spontaneous) amenorrhea, follicle stimulating hormone level ≥40 mIU/mL at Screening, and an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms), or have had surgical bilateral oophorectomy, hysterectomy, or tubal ligation ≥6 weeks prior to Screening; in the case of oophorectomy alone, reproductive status will be confirmed by hormone level assessment;
• A male patient must agree to use adequate contraception (male condom with spermicide or provide evidence of successful vasectomy; sterile sexual partner; or female sexual partner who uses an intrauterine device with spermicide, a female condom with spermicide, a contraceptive sponge with spermicide, an intravaginal system, a double diaphragm with spermicide, a cervical cap with spermicide) from study entry through at least 1 month after the last dose of study drug;

You may not qualify if:

• Disease
• 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;
• Patients who with an allo-transplant of any kind (including those with a xenograft heart valve);
• Any significant ophthalmologic abnormality, including but not limited to the following:
• Grade 2 or greater severity syndrome of dry eye;
• Keratoconjunctivitis sicca;

Sponsors & Collaborators

• Shanghai De Novo Pharmatech Co., Ltd.: lead

Study Sites (3)

University of California San Diego-Moores Cancer Center

La Jolla, California, 92093, United States

Location

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 20237, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Study Design

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

Model Details: A phase Ⅰ,multi-center, open-label

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: May 1, 2019
• Study Start: September 18, 2019
• Primary Completion: August 30, 2022
• Study Completion: October 30, 2022
• Last Updated: November 18, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)