Advanced Solid Tumor
Conditions
Keywords
Advanced Solid Tumor, HS-20105, Trop-2, ADC
Brief summary
HS-20105 is a novel antibody-drug conjugate (ADC) targeting Trop-2. This first-in-human trial is aimed to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics (PK), safety and preliminary anti-tumor activity of HS-20105 in patients with advanced solid tumors.
Detailed description
This is a multicenter, open-label Phase I clinical study evaluating the safety, tolerability, PK, and efficacy of HS-20105 in patients with advanced solid tumors. The study includes Phase Ia (dose escalation) and Phase Ib (dose extension). Phase Ia will conduct a dose escalation using the Rolling 6 design in advanced solid tumor patients who have failed or are unable to tolerate standard treatment, to evaluate the safety, tolerability, PK characteristics, and efficacy of HS-20105. The subsequent Phase Ib study will be conducted in certain population to evaluate the preliminary efficacy of HS-20105 at different doses and in different populations.
Interventions
DRUGHS-20105
Administered intravenously every 21 days.
Sponsors
Hansoh BioMedical R&D Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women aged more than or equal to (≥) 18 years. * Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is failed or intolerable. * Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required). Patients with only brain and/or bone lesions as target lesions will not be included. * Fresh or archived tumor tissue samples need to be provided (fresh samples are preferred, and tumor tissue samples within 2 years before the first administration can be accepted; the sample type is formalin fixed, paraffin embedded \[FFPE\] tumor tissue block or FFPE slides). * ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks. * Estimated life expectancy greater than (\>) 12 weeks. * Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit. * Females must have the evidence of non-childbearing potential. * Sign informed consent form.
Exclusion criteria
* Has received or is currently undergoing the following treatment: 1. Previously or current treatment with drugs targeting Trop-2 or other ADC drugs conjugated with HS-9265; 2. Received traditional Chinese medicine therapy with anti-tumor indications within 2 weeks prior to the first administration of HS-20105; 3. Received cytotoxic chemotherapy drugs or other anti-tumor system therapies (including endocrine therapy, molecular targeted therapy, or biological therapy) within 3 weeks prior to the first administration of HS-20105; 4. Received macromolecular anti-tumor drugs or experimental drug therapy within 4 weeks before the first administration of HS-20105; 5. Received local radiotherapy within 2 weeks before the first administration of HS-20105; Received more than 30% of bone marrow irradiation or extensive radiation therapy within 4 weeks before the first administration of HS-20105; 6. Received major surgery within 4 weeks before the first administration of HS-20105. 7. Received strong inhibitors or inducers of CYP3A4, CYP2D6, P-gp or BCRP, or drugs with narrow treatment windows for CYP3A4, CYP2D6, P-gp or BCRP sensitive substrates, have been used. 8. Receiving medication that is known to prolong the QT interval or may lead to torsade de pointes. * Existing abnormal CTCAE ≥ grade 2 resulted from previous treatment. * History of other malignancy. * Uncontrolled pleural, ascites or pericardial effusion. * Known and unstable central nervous system metastases. * Inadequate bone marrow reserve or serious organ dysfunction. * Severe, uncontrolled, or active cardiovascular disease. * Severe or poorly controlled diabetes. * Severe or poorly controlled hypertension. * Clinically significant bleeding symptoms within 1 month before the first administration of HS-20105. * Serious thrombosis events within 3 months before the first administration of HS-20105. * Serious infection within 4 weeks before the first administration of HS-20105. * Received continuous glucocorticoid treatment for more than 7 days within 28 days before the first administration of HS-20105. * Active infectious disease. * Hepatic encephalopathy, hepatorenal syndrome, or ≥ Child-Pugh B-grade cirrhosis. * Serious or uncontrolled eye disease. * Moderate to severe lung diseases that may interfere with the detection or management of drug-related pulmonary toxicity and seriously affect respiratory function. * Severe neurological or mental disorders that can interfere with assessment. * Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study. * History of hypersensitivity to any active or inactive ingredient of HS-20105. * The subject who is unlikely to comply with study procedures, restrictions, or requirements, judged by the investigator * The subject whose safety cannot be ensured or study assessments would be interfered, judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: MTD or maximum applicable dose (MAD) of HS-20105 | Up to12 months. | Number of participants with DLT. |
| Phase Ib: Efficacy of HS-20105 | Up to 24 months. | Objective response rate (ORR) according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to 24 months. | The time from complete or partial response to disease progression or death, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment. |
| Progression-free survival (PFS) | Up to 24 months. | Progression free survival is defined as the duration of time from study entry to time of progression, death, or is censored at date of last disease assessment. |
| Overall survival (OS) | Up to 3 years | Overall survival is defined as the duration of time from study entry to death or the date of last contact. |
| Maximum plasma concentration (Cmax) | Up to 24 months. | Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. |
| Incidence and severity of treatment-emergent adverse events | Up to 36 months. | Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) | Up to 24 months. | Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration. |
| Elimination half-life (T1/2) | Up to 24 months. | T1/2 is defined as apparent terminal elimination half-life (h). |
| Anti-drug antibodies (ADA) of HS-20105 | Up to 24 months. | Number of participants who are positive for ADA will be reported.. |
| Time of maximum concentration (Tmax) | Up to 24 months. | Tmax is defined as the time required for a drug to reach peak concentration in plasma. |
| Disease control rate (DCR) | Up to 24 months. | The percentage of patients who have achieved complete response, partial response, and stable disease, according to response evaluation criteria in solid tumors (RECIST) 1.1 by investigator's assessment. |
Contacts
Primary ContactBinghe Xu, PhD
Outcome results
None listed