Advanced or metastatic solid tumors
Conditions
Interventions
Part A(Phase I) Dose Escalation:Drug: HMPL-A580
Part A(Phase I) Dose Escalation Enrolled participants will receive HMPL-A580 treatment in a dose escalation setting initially at 6 predefined dose level
Experimental: Part B(Phase IIa) Dose Expansion/Dose Optimization:Drug: HMPL-A580
Part B(Phase IIa) Dose Expansion/Dose Optimization Evaluate the safety and preliminary anti-tumor activity of HMPL-A580
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Fully understand the study and have the ability to voluntarily sign the informed consent form (ICF); 2. Male or female, aged >=18 years old; 3. Histologically confirmed, unresectable, locally advanced or metastatic solid tumors: (1) Dose escalation (Part A) : Histologically confirmed unresectable locally advanced or metastatic solid tumor with failure or intolerance to standard therapy and no standard therapy available. (2) Dose expansion/optimization (Part B) : 1) Cohort 1: unresectable, locally advanced or metastatic EGFR-mutated NSCLC (exon 19 deletion or L858R mutation) after =4 lines of systemic therapy that included combination or sequential therapy with EGFR-TKI and platinum-based chemotherapy. 2) Cohort 2: unresectable, locally advanced, or metastatic KRAS wild-type CRC with =12 weeks; 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-1; 8. Good bone marrow, kidney and liver function: (1) ANC >=1.5×10^9/L, hemoglobin >=9.0 g/dL, and platelet >=75×10^9/L (without granulocyte colony-stimulating factor or other hematopoietic stimulating factor correction within 14 days before laboratory examination, and without platelet transfusion within 7 days before laboratory examination); (2) Creatinine clearance rate > 50 mL/min, which can be calculated by Cockcroft-Gault formula or other clinical trial center detection methods (3) serum total bilirubin <=1.5×ULN; If bilirubin is increased due to Gilbert's syndrome (simple unconjugated hyperbilirubinemia) or liver metastasis, serum total bilirubin <=3× ULN, and there is no other liver dysfunction; (4) ALT and AST<=3×ULN if there is no liver metastasis; <=5×ULN with liver metastasis; (5) international normalized ratio (INR) <=1.5×ULN, or activated partial thromboplastin time (APTT) <=1.5×ULN; 9. Female patients of childbearing potential must use a dual contraceptive method from the start of the screening period, during treatment and up to 7 months after the last dose of study drug and agree not to donate eggs (oocytes) for reproductive purposes during this period; Male patients whose partner was of childbearing potential were also required to use an effective dual contraceptive method during the study and for 4 months after the last study dose and agreed not to donate sperm during this period. Detailed contraceptive guidance is provided in Section 10.3. Female patients who are infertile are exempt from this requirement.
Exclusion criteria
Exclusion criteria: 1. Established type 1 diabetes or uncontrolled type 2 diabetes. (1) Fasting plasma glucose (FPG) >126 mg/dL (7.0 mmol/L) or glycosylated hemoglobin (HbA1c) >6.4%. 2. Use of a CYP3A4 inhibitor, P-gp inhibitor, or BCRP inhibitor 2 weeks before the first dose of a study drug or within five drug half-lives, whichever is longer. 3. Toxicity from previous antineoplastic therapy (other than alopecia) did not return to baseline level of grade 1 before administration of the first study drug. Patients with chronic grade 2 toxicity (e.g., chemotherapy-induced grade 2 neuropathy) were allowed to participate on an individual basis in consultation between the investigator and the sponsor medical monitor. 4. Interval between administration of the first study drug and other previous antineoplastic therapies, including other investigational therapies: (1) Cytotoxic chemotherapy: less than 21 days (2) Systemic small-molecule targeted therapy (e.g., a tyrosine kinase inhibitor) : less than 28 days or five half-lives of the drug, whichever is shorter (3) Nitrosourea: less than 6 weeks (4) Antibody-based therapy: less than 28 days (5) Radiotherapy: 1) Local radiotherapy: less than 14 days 2) Radioisotope therapy: less than 6 weeks 3) 50% pelvic or total body radiotherapy: less than 12 weeks 5. Major surgery within 28 days prior to first study drug administration. Patients had to recover sufficiently from toxicity and/or complications before the first study drug administration. 6. Spinal cord compression, leptomeningeal involvement, or active central nervous system (CNS) metastases, defined as untreated and symptomatic or requiring corticosteroid or anticonvulsant therapy for symptom control. (1)Patients who had received prior treatment for CNS metastases, resolved symptoms after treatment or were neurologically stable and free of steroid therapy for at least 4 weeks prior to enrollment were eligible. 7. Clinically significant cardiovascular disease, including: (1)Acute myocardial infarction occurred within 6 months before the first dose of study drug. (2)Unstable angina or other moderate-to-severe cardiovascular disease-related chest pain that limited activities of daily living occurred =28 days before the first dose of study drug. (3) underwent coronary artery bypass grafting (CABG) within 6 months before enrollment. (4) New York Heart Association (NYHA) grade >=2 congestive heart failure =2 occurred within 6 months before the first dose of study drug. (6) stroke or intracranial hemorrhage occurred =6 months before the first dose of study drug. (7) systolic blood pressure >=160 mmHg and/or diastolic blood pressure >=100 mmHg. Patients had to have blood pressure below these limits, and repeated measurements were allowed. 8. Inherited long QT syndrome, or QTcF>470 msec. 9. History of pulmonary embolism within 3 months before the first dose of study drug. 10. Active infections requiring systemic treatment. 11. Received live or attenuated live vaccine within 3 months before enrollment. 12. Known history of human immunodeficiency virus (HIV) or syphilis infection. 13. Active hepatitis B or hepatitis C: (1)Patients who were positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) were allowed if they were negative for hepatitis B virus (HBV) DNA and did not have an associated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Tolerated Dose (MTD) and/or recommended dose(s) for expansion(RDE);Overview of Treatment-emergent Adverse Events (TEAEs);Objective Response Rate (ORR);Recommended doses for phase II or III studies (RP2D or RP3D) of HMPL-A580; | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (DCR);Progression-free survival (PFS); | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed