This is an open-label, dose-escalation/dose-expansion, phase I clinical trial study to
investigate the safety, tolerability, and efficacy of HWH340. In addition, the
pharmacokinetic characteristics will also be investigated. Three parts are included in this
Part one is a single-dose study on tolerance and pharmacokinetics, in which 21-42 patients
with advanced solid tumors would be enrolled. Patients will receive escalating dose groups of
Part two is a multiple-dose study on tolerance and pharmacokinetics. Based on the safety
assessment, three or four groups would be chosen to conduct the study. 9-24 patients with
advanced solid tumors will be enrolled.
Part three is a dose expansion stage on safety and efficacy. Two to four dose-groups would be
chosen to conduct the study. 40-60 patients with advanced solid tumors with BRCA mutation OR
homologous recombination deficiency (HRD) will be enrolled.
- Patients with the advanced solid tumors, which have been histologically and/ or
- Patients with advanced solid tumors refractory to standard therapy or for whom no
suitable effective standard therapy exists.
- patients in dose expansion stage must meet the following conditions:
- Group 1: Germline and/or systemic BRCA1/2 mutation;
- Group 2: HRD related gene (except BRCA 1/2) mutation;
- For breast cancer patients, Histologically or cytologically confirmed HER2(-), and
received ≤3 prior lines of chemotherapy in advanced or metastatic setting;
- 18 ≤ years of age ≤ 70
- Expected survival time ≥ 6 months
- No serious hematopoietic dysfunction exists. Also, normal function of bone marrow and
organs such as heart, lung, liver and kidney are required. Within 14 days prior to
inclusion, the patients' laboratory examination results must be within normal
limits(under the condition of no extra growth factor or blood transfusion): Blood
routine examination: Absolute neutrophil count( ANC) ≥ 1.5 × 109/L),Platelets(PLT) ≥
100 × 109/L, Hemoglobin(Hb) ≥ 100 g/L;Renal function: Serum creatinine (Cr) ≤1.5×ULN
;Hepatic function: Total Bilirubin ≤1.5×ULN, AST and ALT ≤ 2.5 ×ULN (For patients with
liver metastases, AST and ALT ≤ 5 × ULN) ;Electrolytes: normal value ranges (sodium,
potassium and calcium);Coagulation function: International Normalized Ratio( INR)
≤1.5, Activated partial thromboplastin time(APTT) ≤ 1.5 × ULN;
- Patients of reproductive potential must agree to practice effective medically approved
contraceptive methods during the trial and 6 months afterwards. Women of childbearing
potential must have a negative pregnancy test within 7 days prior to screening.
- Subject must fully understand this study, sign informed consent on a voluntary basis ,
comply with procedures and follow-up examinations as outlined in the protocol and
agree to have the gene test.
- Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 (patients in the
- Multiple-dose patients must have no less than one measurable tumor according to RECIST
- Subject who has other serious and/or uncontrollable damaged vital organs or unstable
systemic disease besides tumors. These diseases include but not limit to uncontrolled
diabetes, unstable angina pectoris , cerebrovascular accident or transient cerebral
ischemia( within 6 months prior to screening), myocardial infarction (within 6 months
prior to screening), congestive heart-failure , uncontrolled high blood pressure,
active or uncontrollable infection, hepatic/renal/metabolic disease, serious
gastrointestinal disease, any mental disease that may affect study abidance ; or any
medical conditions, which in the opinion of the study investigators, places the
subject at an unacceptably high risk of toxicities and interfere with the study.
- Subject who has previously been treated with PARP inhibitors, including any related
clinical trials, except for HWH340. Subjects in dose expansion stage who have
previously received PARP inhibitors (including drug clinical trials), except for
patients who have not reached a therapeutic dose with a PARP inhibitor, or patients
who have used a PARP inhibitor which is not first-line treatment for ≤ 28 days;
- Subject who has received the treatments of inhibitors of CYP3A3 and/or CYP2D6 within 2
- Subject who has received chemotherapy, radiotherapy, endocrinotherapy, biotherapy,
immunotherapy, Chinese herbal treatment or other anti-tumor treatment within 4 weeks
prior to initiation of this study.In the dose expansion stage, except for patients who
have begun bisphosphonate or RANK-L inhibitors with stable dose for bone metastases
- Subject who has participated in other clinical trials or used other investigational
drug within 3 weeks prior to initiation of this study.
- Subject who has the autoimmune disease, immunodeficiency disease or surgical history
of organ transplantation.
- Positive results of HBsAg, HCV antibody, HIV antibody or Syphilis. Patient who has
chronic toxic reaction (≥ CTCAE Grade 2) caused by prophase treatment, except the
- Subject who has experienced major surgery and has not been fully rehabilitated within
4 weeks prior to this study.
- Subject who is allergic to the investigational drug or similar drugs, or has the
history of allergic disease, or is in allergic constitution.
- History of alcohol addiction or abuse.
- Pregnant /lactating women.
- Subject who has the symptoms of CNS metastases.
- History of gastrointestinal dysfunction and difficulty in swallowing that may
influence the drug absorption.
- Subject who has received blood transfusion within 4 weeks prior to the study.
- Subject who attends the study is not on a voluntary basis or cannot comply with the
- Judged by the investigator, for any reason, that the subject is an unsuitable