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.