Solid Tumor
Conditions
Brief summary
This study is a Phase I, multicenter, non-randomized, open-label, first-in-human study of BM230 conducted globally. The study will include two parts: a dose escalation part (Phase Ia) followed by a dose expansion part (Phase Ib). Phase Ia part will estimate the MTD/RED(s) in dose escalation cohorts of patients with advanced solid tumors (HER2-related solid tumors). The Phase Ib part will enroll 5 distinct cohorts of patients with advanced solid tumors related to HER2 under MTD/RED doses, to better define the safety profile of BM230 and evaluate the efficacy of BM230.
Interventions
DRUGBM230
SC injection
Sponsors
Suzhou Biomissile Pharmaceuticals Co., Ltd.
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
Common inclusion criteria (Phase Ia and Phase Ib) (Criteria 1 to 9) Patients must satisfy all the following criteria to be included in the study: 1. Informed of the study before any study-specific procedures are undertaken and voluntarily sign their name and date on the informed consent form (ICF) 2. Males and Females≥18 years old（at the time consent is obtained） 3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 2 4. Life expectancy of ≥ 3 months 5. Adequate organ and bone marrow function, defined as: * Bone marrow function: hemoglobin ≥ 90 g/L (have not received blood transfusion or erythropoietin treatment within 14 days before the first dose); absolute neutrophil count ≥ 1.5×109/L (have not received granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor treatment within 14 days before the first dose); platelet count ≥ 100×109/L ((have not received platelet transfusion, thrombopoietin, or interleukin-11 treatment within 14 days before the first dose) * Coagulation function: activated partial thromboplastin time and international normalized ratio ≤ 1.5 × ULN * Liver function (based on the normal range in the sites): TBIL ≤ 1.5 × ULN if no demonstrable liver lesion(s) (primary or metastases), or ≤ 3 × ULN in the presence of liver lesion(s), or \< 4 × ULN for patients with Gilbert's syndrome; ALT and AST ≤ 3 × ULN if no demonstrable liver lesion(s) (primary or metastases), or ≤ 5 × ULN in the presence of liver lesion(s) * Renal function (based on the normal range in the sites): creatinine clearance (CrCl) calculated by the Cockcroft-Gault formula ≥ 50 mL/min, or 24-h urine CrCl ≥ 50 mL/min * Cardiac function: LVEF ≥ 50%; 6. Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug; a negative pregnancy test must be obtained within 7 days before the first dose. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of study drug 7. Able and willing to comply with protocol visits and procedures 8. Have HER2 expression (IHC 1+, 2+, or 3+) determined by immunohistochemistry, or HER2 amplification (NGS report indicating HER2 amplification) or (for NSCLC) HER2 exon 8, exon 19, or exon 20 mutations. For Australia, only the cancer types with HER2 expression, amplification or mutation assay covered by Australia Pharmaceutical Benefits Scheme, and/or the patients with known HER2 expression, amplification or mutation obtained by any other program, will be considered to be enrolled 9. Willing to provide archived or fresh tumor tissue samples. Patients who are unable to provide tumor samples or have insufficient samples may be eligible on a case-by-case basis after discussion with the sponsor Additional inclusion criteria for Phase Ia (Criteria 10 to 11) 10. Pathologically confirmed diagnosis of locally advanced or metastatic solid tumors (BC, GC, CRC, and NSCLC are preferable), for which prior standard treatment had proven to be ineffective or intolerable, or no standard treatment is available, or the patient refuses standard treatment 11. Have at least one measurable tumor target lesion according to RECIST version 1.1. Patients in the accelerated titration cohort are not required for the above mentioned measurable tumor target lesion Additional inclusion criteria for Phase 1b (Criteria 12 to 13) 12. For Cohort A: BC patients: * Have a pathologically documented advanced/unresectable or metastatic BC * Have disease progression on or after the last treatment or intolerance to the last treatment, or for which no standard treatment is available For Cohort B: GC patients: * Have a pathologically documented advanced/unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma * Have disease progression on or after prior treatment with at least one line of PD-(L)1 inhibitors and/or chemotherapy under metastatic setting For Cohort C: CRC patients: * Have a pathologically documented advanced/unresectable or metastatic CRC * Have disease progression on or after the last treatment or intolerance to the last treatment, or for which no standard treatment is available For Cohort D: NSCLC patients: * Have a pathologically documented Stage IIIB, IIIC, or IV squamous or non-squamous NSCLC * Have disease progression on or after prior anti-PD-(L)1 treatment and platinum-based chemotherapy * Have disease progression on or after prior on all targeted therapy for patients with mutations eligible targeted therapy For Cohort E (basket cohort): patients with other HER2-related solid tumors, including but not limited to ovarian cancer, endometrial cancer, cervical cancer, cholangiocarcinoma, pancreatic cancer, bladder cancer, and prostate cancer: • Have a pathologically documented advanced/unresectable or metastatic tumorHave disease progression on or after the last treatment or intolerance to the last treatment, or for which no standard treatment is available 13. At least one evaluable tumor target lesion according to RECIST version 1.1
Exclusion criteria
Patients who meet any of the following criteria will NOT be included in the study: Common
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLT | 21 days | Dose limiting toxicity |
| AEs | up to 3 years | Adverse events |
| MTD and/or RED | up to 3 years | The maximum tolerated dose (MTD) and/or the recommended expansion dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC | up to 3 years | area under the concentration-time curve |
| Cmax | up to 3 years | maximum concentration |
| Ctrough | up to 3 years | trough concentration |
| CL | up to 3 years | clearance rate |
| Vd | up to 3 years | volume of distribution |
| t1/2 | up to 3 years | half-life time |
| ADA | up to 3 years | Anti-drug antibody |
| ORR | up to 3 years | Objective response rate assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| DCR | up to 3 years | Disease control rate (DCR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| DoR | up to 3 years | Duration of response (DoR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| BOR | up to 3 years | Best overall response (BOR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| TTR | up to 3 years | Time to response (TTR) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| PFS | up to 3 years | Progression-free survival (PFS) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| OS | up to 3 years | Overall survival (OS) assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Countries
Australia, China
Contacts
CONTACTRui Liu, Ph.D.
CONTACTTing Yu
Outcome results
None listed