advanced solid tumour
Conditions
Interventions
Intervention group:DM005
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Common inclusion criteria for both Parts:; 1. Participants must have the ability to understand and willingness to sign a written informed consent document. 2. Participants who have pathologically or cytologically documented metastatic/advanced NSCLC, SCLC, gastroesophageal cancer, CRC, HCC, pancreatic cancer, or HNSCC, not curable with standard local therapies (i.e., surgery and/or radiation) and have progressed on standard therapy, or intolerant to standard therapy. 3. Participants must be >=18 years of age on the day of signing the informed consent form (ICF). 4. Participants must have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2. 5. Has a life expectancy >=3 months. 6. Participants must meet the following laboratory values within 7 days prior to first dose of study drug: Note: Transfusion (red blood cell or platelet) or granulocyte-colony stimulating factor (GCS F) administration is not allowed within 2 weeks prior to laboratory assessments at Screening.• Absolute neutrophil count (ANC) >=1.5 × 109/L; • Platelet count >=100 × 109/L; • Hemoglobin >=9 g/dL; • Calculated creatinine clearance (CrCL) >60 mL/min (Cockroft-Gault Equation); • AST and ALT <=3.0 × ULN, if liver metastases are present, <=5 × ULN; • International normalized ratio (INR)<2.0/prothrombin time and either partial thromboplastin time (PTT) or activated PTT (aPTT) <=1.5 × ULN, except for participants receiving anti-vitamin K derivative anticoagulant therapy who must have PT/INR within therapeutic range as deemed appropriate by the Investigator. 7. Has measurable disease based on RECIST version 1.1. 8. Participants are required to provide tumor tissue specimens obtained within the previous 3 years for the measurement of c-MET and/or EGFR and other biomarkers. For those subjects who are unable to provide tissue samples will be encouraged (but not mandatory) to undergo biopsy if the risk is manageable. If the biopsy is not possible, it should inform the sponsor for enrollment. Additional inclusion criteria for Part 2:; 9.(Dose Expansion, Cohort 2A):9. Histologically or cytologically confirmed metastatic or locally advanced EGFRmut. NSCLC patients who have been treated with at least 1 prior line of systemic anticancer therapy. EGFR mutations include but not limited to EGFR Exon 19 deletions, or Exon 21 L858R mutations, exon 20 insertion mutations, or others, these patients should have had prior disease progression on or after treatment with a third generation EGFR-TKI and platinum-based chemotherapy, patients with other EGFR mutations should have had prior disease progression on or after treatment with platinum-based chemotherapy, an EGFR-TKI should also be used if any per local guidance. 10.(Dose Expansion, Cohort 2B):10. Histologically or cytologically confirmed metastatic or locally advanced EGFRwt. NSCLC patients, either with or without other actionable genomic alterations (e.g., in ALK, ROS1, BRAF, MET, RET, HER2, NTRK), who have been treated with at least 1 prior line of systemic anticancer therapy. Patients should have had prior disease progression on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1 antibody (either given concurrently or sequentially). * Patients who have not received prior treatment should be made fully aware that there are regional authority approved available therapies for the treatment of participants with advanced NSCLC with known survival benefit that participants may be forgoing by e
Exclusion criteria
Exclusion criteria: 1. Participants have another active invasive malignancy within 5 years, with the following exceptions and notes: • History of noninvasive malignancy, such as cervical cancer in situ, in situ melanoma, or ductal carcinoma in situ of the breast that is in complete remission years after treatment with curative intent is allowed. • Malignancies with a negligible risk of metastasis or death (such as adequately treated basal or squamous cell skin cancer and localized prostate cancer). 2. Current or history of hematologic malignancy. 3. Anticancer therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-cancer therapies, except for hormones for hypothyroidism or estrogen replacement therapy, anti estrogen analogs, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter, prior to the first study dose. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limitedfield of radiation for palliation within 14 days of the first study dose. Major surgery, other than diagnostic surgery, within 4 weeks of the first study dose. 4. Primary central nervous system (CNS) malignancies or CNS metastases. Symptomatic brain metastases (asymptomatic brain metastases stable at least 2 months can be enrolled). 5. Presence of bulky disease (defined as any single mass >7 cm in its greatest dimension). Individuals with a mass >7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor. 6. History of allergy to ADC or prior discontinuation of an ADC due to treatment-related toxicities. Has received prior treatment with EGFR or MET targeted ADCs. 7. Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals. 8. Has clinically significant corneal disease. 9. Has a medical history of clinically significant lung diseases (e.g., ILD, non-infection pneumonitis, pulmonary fibrosis, and radiation pneumonitis) or who is suspected to have these diseases by imaging at screening period. 10. Clinically uncontrolled intercurrent illness, including but not limit to an ongoing active infection, active coagulopathy, uncontrolled cardiovascular disease, uncontrolled immune disease, uncontrolled diabetes, uncontrolled pleural and peritoneal effusion, psychiatric illness that would limit compliance with the study requirements and other serious medical illnesses requiring systemic therapies. 11. Has a corrected QT interval (QTcF) prolongation to >470 ms (for both genders) based on average of the Screening triplicate 12-lead ECG determinations; no concomitant medications that would prolong the QT interval; no known family history of long QT syndrome. 12. Left ventricular ejection fraction (LVEF) <50% by either an echocardiogram (ECHO) or a multigated acquisition (MUGA) scan within 28 days before first dose of the study drug. 13. Known active hepatitis B (HBV) or hepatitis C (HCV) infection. Chronic carriers of HBV infection (HBsAg-positive, undetectable HBV DNA or HBV DNA =2500 copies/ml or 500 IU/ml) receive prophylactic treatment during the study can be enrolled. Participants with a history of HCV infection have completed curative antiviral treatment and HCV viral load below the limit of quantification and HCV antibody positive but HCV ribonucleic acid (RNA) negative due to prior treatment or natural resolution should be eligible. 14. Known human immunodeficiency
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety analysis set (SS); | — |
Countries
China
Contacts
Public ContactJinji Yang
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed