Advanced Solid Tumors
Conditions
Keywords
ADC, advanced solid tumors, EGFR, HER3
Brief summary
The goal of this clinical trial is to learn if the study drug can work in advanced cancer patients. The main questions it aims to answer are: * Is the drug safe and tolerable ? * Does the drug exhibit antitumor activity ? Participants will receive the study drug once every three weeks, and imaging-based efficacy assessments will be performed every six weeks.
Detailed description
Target population are patients with advanced solid tumors .
Interventions
DRUGHDM2024
ADC drug targeting EGFR and HER3
Sponsors
Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Participants who voluntarily participate in this study and sign the written Informed Consent Form (ICF) after being fully informed. * 2\. Male or female participants aged 18 to 75 years (inclusive). * 3\. Participants with histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors who have experienced disease progression on or after standard therapy , or are intolerant to standard therapy, or for whom no effective standard of care is available. * 4\. Participants who are able to provide fresh or archival tumor tissue during the screening period. Tumor tissue will be collected for biomarker testing at a central laboratory, including immunohistochemistry for EGFR and HER3 . * 5\. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 . * 6\. Life expectancy ≥3 months. * 7\. According to RECIST v1.1, the participant must have at least one measurable lesion . * 8\. Participants with good organ function as demonstrated by screening laboratory test results. * 9\. The fertile participants agreed to take effective contraceptive measures during the study and after its conclusion; and must have a negative serum human chorionic gonadotropin (HCG) test within 7 days before dosing. * 10\. Participants should be willing and able to complete regular visits, treatment plans, laboratory tests, and other study procedures.
Exclusion criteria
* 1\. Participants who have previously received ADC containing exatecan , or an ADC primarily directed against EGFR and/or HER3. * 2\. Participants who have received the following treatments: 1. Participants who have undergone major surgery within 4 weeks before the first dose; 2. Participants who have received radiotherapy involving the bone marrow or extensive radiotherapy within 4 weeks before the first dose; or local radiotherapy within 2 weeks before the first dose; 3. Participants who are receiving continuous systemic corticosteroid therapy ; low-dose corticosteroids are permitted if the dose of systemic corticosteroids has been stable for 4 weeks; 4. Participants who have received anti-tumor treatments within 4 weeks before the first dose, or are still within 5 half-lives of the last dose of the most recent anticancer therapy (whichever is longer). Traditional Chinese medicines with approved anticancer indications within 2 weeks prior to the first administration of study drug. * 3\. Participants with other malignant tumor within the past 5 years, other than the tumor treated in this study, with the exception of locally cured tumors . * 4\. Participants with related AEs (except for alopecia and ≤ Grade 2 sensory neuropathy) caused by previous treatment that have not recovered to ≤ Grade 1 or baseline level. * 5\. Participants with known weight loss of \>10% within 2 months before the first dose of the study drug or other indicators showing severe malnutrition. * 6\. Participants with serious complications or medical histories involving important organs. * 7\. Participants with known active central nervous system (CNS) metastasis. * 8\. Participants with any of the cardiovascular/cerebrovascular disorders, symptoms, or manifestations. * 9\. Participants with the following conditions will be excluded at screening: active syphilis, history of human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) or active hepatitis C virus (HCV), with the exception of asymptomatic chronic hepatitis B or C virus carriers. * 10\. Participants with a history of interstitial pneumonia or other moderate to severe lung disorders that seriously affect lung function. * 11\. Participants with severe infection during the screening period. * 12\. Participants with other diseases that may affect the efficacy and safety of the study drug. * 13\. Participants with uncontrolled pericardial effusion, uncontrolled pleural effusion, or clinically significant moderate or greater ascites during the screening period. * 14\. Participants with unstable thrombotic events requiring therapeutic intervention within 6 months before screening; however, thrombosis related to infusion devices is not included. * 15\. Participants who have received a live vaccine within 30 days before the first dose, or plan to receive a live vaccine during the study period. * 16\. Participants who have received strong CYP3A4 inhibitors and inducers therapy within 1 week before dosing, or are expected to require long-term use of strong CYP3A4 inhibitors and inducers during the study intervention and within 30 days after the last dose . * 17\. Participants with history of solid organ transplant. * 18\. Participants with known or suspected history of severe allergy to any component of the study drug or its analogues. * 19\. Pregnant and lactating women. * 20\. Participants who are deemed unsuitable for this study (e.g., poor compliance, etc.) by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal tolerance dose (MTD) of HDM2024 | DLT will be evaluated on 21 days of observation period | The MTD is defined as the dose level at which the estimated toxicity probability is closest to the target toxicity rate during the Dose-limiting toxicity (DLT) observation period of the dose escalation stage. |
| Determination of the Recommended Phase 2 dose (RP2D) | Approximately 1 years | — |
| Incidence and severity of Treatment-Emergent Adverse Events | Approximately 1 years | Incidence rates of adverse events (AE), serious adverse events (SAE)per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v6.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to peak (Tmax) of HDM2024 | Approximately 1 years | Tmax of HDM2024, total antibody, and exatecan will be measured |
| Half-life time (t1/2) of HDM2024 | Approximately 1year | t1/2 of HDM2024, total antibody, and exatecan will be measured |
| Peak Plasma Concentration (Cmax) of HDM2024 | Approximately 1 year | Cmax of HDM2024, total antibody, and exatecan will be measured |
| Area under the plasma concentration versus time curve (AUC) of HDM2024 | approximately 1 year | AUC of HDM2024, total antibody, and exatecan will be measured |
| Objective response rate (ORR) | Approximately 1 year | ORR assessed based on RECIST v1.1 criterion |
| Disease control rate (DCR) | Approximately 1 year | DCR assessed based on RECIST v1.1 criterion |
| Progression-free survival (PFS) | Approximately 1year | PFS assessed based on RECIST v1.1 criterion |
| Overall survival (OS) | Approximately 1 year | OS of 6-months and 12-months |
Countries
China
Contacts
CONTACTZhou Caicun
Outcome results
None listed