Clinical Trials /

Study of DP303c Administered Intravenously to Subjects With HER2-Positive in Advanced Solid Tumors

NCT04146610

Description:

A phase Ia, multicenter, open and dose-increasing study of DP303c to evaluate the safety , pharmacokinetics, immunogenicity and antitumor activity of subjects with HER2-positive advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of DP303c Administered Intravenously to Subjects With HER2-Positive in Advanced Solid Tumors
  • Official Title: A Phase Ia, Multicenter, Open and Dose-increasing Study of DP303c to Evaluate the Safety , Pharmacokinetics, Immunogenicity and Antitumor Activity of Subjects With HER2-Positive Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: DP303c201801
  • NCT ID: NCT04146610

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
an antibody drug conjugateADCDp303c

Purpose

A phase Ia, multicenter, open and dose-increasing study of DP303c to evaluate the safety , pharmacokinetics, immunogenicity and antitumor activity of subjects with HER2-positive advanced solid tumors.

Detailed Description

      Dose escalation study: Primary purpose: To investigate the safety and tolerability of DP303c
      in subjects with HER2-positive advanced solid tumors . Secondary purpose:1. To characterize
      the pharmacokinetics(PK) profile of DP303c;2. To assess the preliminary anti tumor activity
      of DP303c; 3. To characterize immunogenicity of DP303c.
    

Trial Arms

NameTypeDescriptionInterventions
Dp303cExperimentalMultiple dose grouping
  • an antibody drug conjugate

Eligibility Criteria

        Inclusion Criteria:

          -  Voluntary agreement to provide written informed consent;

          -  Aged 18 to 75 years, both male and female;

          -  Patients with advanced solid tumors diagnosed by histology and / or cytology,
             confirmed to be HER2 positive by pathological examination, unable to accept or have no
             standard treatment, failure of standard treatment (disease progress or treatment
             without remission after treatment) or intolerable patients; HER2-positive is defined
             as IHC 2+ and ISH positive or IHC 3+; IHC scores of breast cancer and gastric cancer
             are based on their respective standards, while IHC scores of other cancers are based
             on the scoring standards of breast cancer;

          -  The ECOG performance status is 0 to 1,and the expected survival time is more than 3
             months;

          -  Subjects must have laboratory values within the limits described below:

        ANC ≥1.5 x 109/L Platelet count ≥100 x 109/L Hemoglobin ≥9 g/dL Serum creatinine within
        normal limits OR creatinine clearance ≥60 mL/minute Serum total bilirubin ≤1.5 x ULN (up to
        3 x ULN in subjects with Gilbert's syndrome) AST (SGOT) and ALT (SGPT) ≤2.5 x ULN (OR ≤5 X
        ULN for subjects with liver metastases) PT/INR and APTT ≤1.5 x ULN

          -  According to the RECIST v1.1 standard, there must be a measurable lesion at the base
             line;

          -  WOCBP must have a negative pregnancy test prior to study entry;

          -  WOCBP and male subjects must agree to use adequate contraception from study entry
             through at least 12 weeks after the last dose of study drug (see Appendix 5);

          -  A washout period is required for subjects who have recently received systemic
             antitumor therapy. The period prior to the subject's planned first dose of DP303c must
             be either at least 28 days or 5 half-lives, whichever is shorter. Antitumor therapy
             includes chemotherapy, immunotherapy, targeted therapy, endocrine therapy,
             radiotherapy (except local radiotherapy for pain relief, 14 days after treatment).

        Exclusion Criteria:

          -  Pregnant or breastfeeding women;

          -  Refusal to use effective methods of contraception (see inclusion criteria for
             details);

          -  Not recovered from AEs caused by previous drugs or radiotherapy (reference NCI CTCAE
             5.0, ≤Grade 1 or at baseline), with the exception of alopecia;

          -  History of cardiac dysfunction with LVEF <40% while on trastuzumab therapy;

          -  Subjects with a history of allergy to any components(tratozumab analogues, MMAE,
             sodium citrate dihydrate, citrate monohydrate, polysorbitol 20 and sucrose, etc.) of
             DP303cand those who researchers consider to be more serious;

          -  A history of central nervous system (CNS) metastases or epilepsy, asymptomatic or
             stable, and not requiring treatment at least 4 weeks before study therapy began;

          -  Active lung infection or pneumonitis or a history of non-infectious interstitial lung
             disease;

          -  Requires supplemental oxygen;

          -  History of congestive heart failure, unstable angina pectoris, unstable atrial
             fibrillation, or cardiac arrhythmia. Subjects who have the following types of cardiac
             impairment at the time of enrollment:

        New York Heart Association class III or IV heart disease Uncontrolled angina, congestive
        heart failure, or myocardial infarction within 6 months prior to enrolment An LVEF by
        echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan <50% or below the lower limit
        of normal for the institution QT interval prolongation (>450 ms in males, >470 ms in
        females),QT interval correction (QTcF) was corrected by Fridericia formula

          -  In the first 90 daysof the study, Cumulative anthracycline dose ≥360 mg/m2 doxorubicin
             or equivalent;

          -  Peripheral neuropathy ≥Grade 2 or greater (NCI CTCAE v 5.0);

          -  12.Non-manageable electrolyte imbalances including hypokalemia, hypocalcemia, or
             hypomagnesemia (≥Grade 2 or greater based on NCI CTCAE v 5.0);

          -  Any uncontrollable intercurrent illness, infection, or other conditions that could
             limit study compliance or interfere with assessments;

          -  Serologic status reflecting active hepatitis B or C infection;

          -  Subjects with immunodeficiency, including HIV positive;

          -  Patients were treated with CYP3A inhibitors within 14 days of the first dose (drugs
             that increased specific CYP substrate AUC ≥ 5 times, such as Mibefradil, verapamil,
             diltiazem, nefazodone, clarithromycin, Telithromycin, Troleandomycin, Erythromycin,
             fluconazole, itraconazole, ketoconazole,
             Posaconazole,VoriconazoleTablets,Elvitegravir,indinavir,lopinavir,
             Nelfinavir,Ritonavir,Saquinavir, Boceprevir,Incivo,telaprevir,Conivaptan,idelalisib)
             or strong CYP3A inducers (Avasimibe, phenobarbital, phenytoin,
             carbamazepine,Rifampicin, rifabutin,enzalutamide, mitotane, Hypericum perforatum );

          -  Other serious or uncontrollable diseases or conditions that may affect the assessment
             of the primary endpoint or that the investigator considers to be at risk for
             participants participating in this study.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximal Tolerance Dose (MTD) of Dp303c
Time Frame:The first treatment cycle 21 days
Safety Issue:
Description:The dose level in which >= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level.

Secondary Outcome Measures

Measure:Maximum concentration (Cmax) of DP303c
Time Frame:approximately 2 years
Safety Issue:
Description:The pharmacokinetics(PK) profile of DP303c
Measure:Time of peak plasma concentration (Tmax)
Time Frame:approximately 2 years
Safety Issue:
Description:The pharmacokinetics(PK) profile of DP303c
Measure:Area under the plasma concentration time curve (AUC) of DP303c
Time Frame:approximately 2 years
Safety Issue:
Description:The pharmacokinetics(PK) profile of DP303c
Measure:Overall response rate (ORR)
Time Frame:approximately 2 years
Safety Issue:
Description:To preliminarily evaluate ORR in patients with advanced solid tumors.
Measure:Duration of Response (DoR)
Time Frame:approximately 2 years
Safety Issue:
Description:To preliminarily evaluate DoR in patients with advanced solid tumors.
Measure:Immunogenicity (anti-drug antibody ADA)
Time Frame:approximately 2 years
Safety Issue:
Description:Percentage of subjects producing detectable anti-drug antibodies (ADA)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Last Updated

October 29, 2019