Advanced Solid TumorsPhase 1NCT03415659
Phase I Clinical Study of HWH340 Tablet in Patients With Advanced Solid Tumors
A Phase 1 study testing HWH340 tablet in people with Advanced Solid Tumors and HRD, run by Hubei Biological Medicine Industrial Technology Institute Co., Ltd. at 1 site in China.
Trial summary
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 study. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Solid Tumors, HRD, BRCA Mutation
- What is being tested?
- HWH340 tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 1 siteChina
- Study dates
- 5 Mar 2018to 30 Sep 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with the advanced solid tumors, which have been histologically and/ or cytologically confirmed.
- 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;
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- 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 study)
- Multiple-dose patients must have no less than one measurable tumor according to RECIST 1.1 criteria.
Who cannot join
- 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 weeks.
- 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 before enrollment.
- 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.
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- 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 hair-loss patients.
- 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 protocol.
- Judged by the investigator, for any reason, that the subject is an unsuitable candidate.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tianjin medical university cancer insititute & hospital
Tianjin, Tianjin Municipality, 300060
Tong Zhongsheng, +86-18622221181, 18622221181@163.com
About this study
Official title: A Phase I, Open-label, Single-center, Single/Multiple-dose, Dose-escalation/Dose-expansion Clinical Study on Tolerance and Pharmacokinetics of HWH340 Tablet in Patients With Advanced Solid Tumors
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 study.
Read the detailed description
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 HWH340 tablet.
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.
- Conditions
- Advanced Solid Tumors, HRD, BRCA Mutation
- Being tested
- HWH340 tablet
- Keywords
- HWH340, pharmacokinetics, dose-escalation, safety, efficacy, dose-expansion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HWH340 tabletDrug
- single escalating dose study starts from 20 mg as the initial dose until the maximum dose group (520mg) or maximum tolerated dose (MTD) has been reached.
- multiple-dose study conducted on oral HWH340 tablet BID. The DLTs evaluating period is 4 weeks and the safety evaluation period lasts till 4 weeks after drug withdrawal.
- dose-expansion study conducted on oral HWH340 tablet BID in 2 to 4 dose groups. Patients with BRCA mutation OR HRD will be assigned to 2 cohort in each dose group.
| Study group | Role | What they receive |
|---|---|---|
| HWH340 monotherapy | Experimental | HWH340 tablet, oral administration Receives: Drug: HWH340 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose
Number of Participants with adverse events
Measured: up to 7 days after dosing
Number of Participants With Laboratory Test Abnormalities on single dose
The laboratory test included: hematology, chemistry, urinalysis, and other tests
Measured: up to 7 days after dosing
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) on multiple dose
Number of Participants with adverse events
Measured: up to 30 days after dosing
Number of Participants With Laboratory Test Abnormalities on multiple dose
The laboratory test included: hematology, chemistry, urinalysis, and other tests
Measured: up to 30 days after dosing
Secondary outcomes (10)
Maximum Observed Plasma Concentrations of platinum (Cmax)
Blood samples are obtained and plasma concentrations of HWH340 are determined using a validated atomic absorption spectrometry method.
Measured: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Tumor Objective Response Rate（ORR）
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: on day 42 post dose
Area under the plasma concentration versus time curve (AUC)
AUC referred to area under the plasma concentration-time curve post dose.
Measured: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Time for Maximum Observed Plasma Concentration (Tmax)
Blood samples are obtained and plasma concentrations of HWH340 are determined using a validated atomic absorption spectrometry method.
Measured: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Disease Control Rate (DCR)
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Objective Response Rate by Investigator
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Disease control rate
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Duration of response
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Best overall response
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Progression Free Survival
Response and progression is evaluated using internationally accepted response criteria and definitions proposed by the RECIST criteria.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2018
- Study start5 Mar 2018
- Primary completion30 Mar 2021 (estimated)
- Study completion30 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hubei Biological Medicine Industrial Technology Institute Co., Ltd.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- TONG Zhongsheng, Principal investigator, Professor of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03415659
- Sponsor's protocol ID
- HWH340-RFPA 20170821
- Status last verified
- Feb 2020
- First submitted
- 16 Jan 2018
- Last updated
- 17 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zhang J, Wang X, Xu H, Zang A, Zhao J, Chen J, Lei R, Zhang Z, Hao C, Liu Y, Zhou R, He L, Sun T, Ouyang Q, Chen S, Xu J, Zhou W, Shi Y, Tong Z. First-in-Human Study of the PARP Inhibitor HWH340 in Advanced Solid Tumors with Enrichment for Homologous Recombination Repair Gene Mutations. Drug Des Devel Ther. 2026 Sep 5;20:606617. doi: 10.2147/DDDT.S606617. eCollection 2026.
PubMed 42724016
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-label, Single-center, Single/Multiple-dose, Dose-escalation/Dose-expansion Clinical Study on Tolerance and Pharmacokinetics of HWH340 Tablet in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03415659
- Acronym / sponsor ID
- HWH340-RFPA 20170821
- Conditions
- Advanced Solid Tumors, HRD, BRCA Mutation
- Keywords
- HWH340, pharmacokinetics, dose-escalation, safety, efficacy, dose-expansion
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 85 participants (estimated)
- Lead sponsor
- Hubei Biological Medicine Industrial Technology Institute Co., Ltd.University, hospital or other
- Study start
- 5 Mar 2018 (actual)
- Primary completion
- 30 Mar 2021 (estimated)
- Study completion
- 30 Sep 2021 (estimated)
- First posted
- 30 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 study.
Detailed description
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 HWH340 tablet.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HWH340 monotherapy | Experimental | Drug: HWH340 tabletHWH340 tablet, oral administration |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with the advanced solid tumors, which have been histologically and/ or cytologically confirmed.
- 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;
Key exclusion criteria (16 listed)
- 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 weeks.
- 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 before enrollment.
- Subject who has participated in other clinical trials or used other investigational drug within 3 weeks prior to initiation of this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HWH340 tablet1. single escalating dose study starts from 20 mg as the initial dose until the maximum dose group (520mg) or maximum tolerated dose (MTD) has been reached. 2. multiple-dose study conducted on oral HWH340 tablet BID. The DLTs evaluating period is 4 weeks and the safety evaluation period lasts till 4 weeks after drug withdrawal. 3. dose-expansion study conducted on oral HWH340 tablet BID in 2 to 4 dose groups. Patients with BRCA mutation OR HRD will be assigned to 2 cohort in each dose group. | Drug | HWH340 monotherapy |
Primary outcome
Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose
Time frame: up to 7 days after dosing
Number of Participants with adverse events
Number of Participants With Laboratory Test Abnormalities on single dose
Time frame: up to 7 days after dosing
The laboratory test included: hematology, chemistry, urinalysis, and other tests
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) on multiple dose
Time frame: up to 30 days after dosing
Number of Participants with adverse events
Number of Participants With Laboratory Test Abnormalities on multiple dose
Time frame: up to 30 days after dosing
The laboratory test included: hematology, chemistry, urinalysis, and other tests
10 secondary outcomes
Maximum Observed Plasma Concentrations of platinum (Cmax)
Time frame: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Tumor Objective Response Rate（ORR）
Time frame: on day 42 post dose
Area under the plasma concentration versus time curve (AUC)
Time frame: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Time for Maximum Observed Plasma Concentration (Tmax)
Time frame: Prior to 0 hour, and 0.5, 1, 2, 4, 8, 12, 36 and 48 hours post dose
Disease Control Rate (DCR)
Time frame: through study completion, an average of 1 year
Objective Response Rate by Investigator
Time frame: through study completion, an average of 1 year
Disease control rate
Time frame: through study completion, an average of 1 year
Duration of response
Time frame: through study completion, an average of 1 year
Best overall response
Time frame: through study completion, an average of 1 year
Progression Free Survival
Time frame: through study completion, an average of 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Derived from this study: PubMed 42724016Zhang J, Wang X, Xu H, Zang A, Zhao J, Chen J, Lei R, Zhang Z, Hao C, Liu Y, Zhou R, He L, Sun T, Ouyang Q, Chen S, Xu J, Zhou W, Shi Y, Tong Z. First-in-Human Study of the PARP Inhibitor HWH340 in Advanced Solid Tumors with Enrichment for Homologous Recombination Repair Gene Mutations. Drug Des Devel Ther. 2026 Sep 5;20:606617. doi: 10.2147/DDDT.S606617. eCollection 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
TONG Zhongsheng principal investigator
Professor of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HWH340 tablet in people with Advanced Solid Tumors and HRD, run by Hubei Biological Medicine Industrial Technology Institute Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact HE Zhenyu (+86-027-87171568, hezhenyu@renfu.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) and recommended dose (RD) by evaluating the safety and tolerability on single dose (time frame: up to 7 days after dosing). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03415659, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.