Advanced Malignant Solid Tumors
Conditions
Interventions
Dose escalation phase:Take HMPL-415S1 orally
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Fully understand this study and voluntarily sign the ICF; 2. Age 18-75 years (inclusive); 3. Patients receiving intermittent treatment in dose escalation phase, and all patients in dose expansion phase: be willing and available to provide tissue samples for biomarker testing; 4. Dose escalation phase: patients with histologically or cytologically confirmed advanced malignant solid tumors, who have failed or been intolerant to the standard treatment, or who cannot receive or have no standard treatment for various reasons Dose expansion phase: patients with histologically or cytologically confirmed advanced malignant solid tumors, who have failed or been intolerant to the standard treatment, or who cannot receive or have no standard treatment for various reasons, carrying aberrant activating mutations in the KRAS pathway, including KRAS G12C, KRASG12V, BRAF Class 3 (RAS-mediated BRAF mutations of low kinase activity or kinase-inactive), NF1LoF mutations, and RTKs (eg, EGFR, MET, HER2, FGFRs, etc) mutations, amplifications, or rearrangements. Tumor types include but are not limited to advanced NSCLC, HNSCC, ESCC, CRC, and other tumor types that suggest clinical benefit during dose escalation or have evidence from drugs of the same target. 5. Presence of at least one measurable lesion (RECIST 1.1 criteria) note: a lesion priorly irradiated should not be considered a target lesion unless there is radiographic evidence of unequivocal progression following radiotreatment; 6. Eastern Cooperative Oncology Group (ECOG) performance status score = 1; 7. Life expectancy = 12 weeks as judged by the investigator; 8. Adequate bone marrow, liver and kidney organ function (no whole blood transfusion, component transfusion, blood products, no use of granulocyte CSF or other hematopoietic stimulating factors or drug correction within 2 weeks before blood collection): • Absolute neutrophil count = 1.5×10^9 /L; (1) Hemoglobin >=90 g/L; (2) Thrombocyte count >=100×10^9 /L; (3) Serum total bilirubin (TBIL) =60 mL/min (calculated according to Cockroft-Gault formula); (6) International normalized ratio (INR) 50 years of age and >1 year of menolipsis in the absence of other biological or physiological reasons) and female who underwent irreversible sterilization surgery (including amputation of uterus, oophorectomy bilateral, or bilateral salpingectomy, but not tubal ligation) will not be considered to be of childbearing potential.
Exclusion criteria
Exclusion criteria: 1. Pregnancy or breast-feeding female patients; 2. Patients with primary hepatic carcinoma or pancreatic carcinoma; 3. Prior antitumor treatment consistent with any of the following: a. Patients who priorly received SHP2 inhibitors;b. Received the approved systemic antitumor treatment within 4 weeks prior to the first dose, including: chemotherapy, targeted treatment, immune treatment, biological treatment, etc. (wash-out for 2 weeks for hormone treatment or traditional chinese medicine and chinese patent medicine with clear antitumor indications);c. Have been in the treatment period of other interventional clinical studies (including small molecule chemicals and large molecule antibodies) within 4 weeks prior to the first dose. Patients can be enrolled if participating in a non-interventional clinical study (eg, epidemiological study), or already in the survival follow-up period of an interventional clinical study. d. Major surgery or radical radiotherapy (except palliative radiotreatment for metastases to bone lesions) within 4 weeks prior to first dose. 4. Toxicities related to prior tumor treatment (including surgery, chemotherapy, radiotherapy, targeted treatment, and immune treatment, etc.) have not recovered to 450 msec or take drugs known to prolong QT interval or torsades de pointes; (1) Severe arhythmia or conduction abnormality requiring clinical intervention; (2) Impaired cardiac function or clinically significant cardiac disorder, including but not limited to the following conditions within 6 months prior to enrollment: acute myocardial infarction, unsteadiness anginal pain, coronary artery bypass surgery, New York Heart Association Class III/IV hyperemia heart failure, and left ventricular ejection fraction (LVEF) < 50%; • Uncontrolled h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| adverse event ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective relief rate, ORR;Overall survival, OS;During of response, DOR;time to response, TTR;Disease control rate, DCR;Progression free survival, PFS; | — |
Countries
China
Contacts
Public ContactTianshu Liu
Zhongshan Hospital, Fudan University
Outcome results
None listed