Advanced Solid Tumor
Conditions
Interventions
Group 1:0.1 mg/kg T320 for injection,Q3W
Group 2:0.4 mg/kg T320 for injection,Q3W
Group 3:1.0 mg/kg T320 for injection,Q3W
Group 4:1.5 mg/kg T320 for injection,Q3W
Group 5:1.8 mg/kg T320 for injection,Q3W
Group 6:2.0 mg/kg T320 for injection,Q3W
Group 7:2.2 mg/kg T320 for injection,Q3W
Cohort 1: Cervical Cancer:2.0 mg/kg T320 for injection,Q3W
Cohort 2: Pancreatic Cancer:2.0 mg/kg T320 for injection,Q3W
Cohort 3: Other Cancers (HNSCC, NSCLC, Ovarian or Endometrial Cancer):2.0 mg/kg T320 for injection,Q3W
Sponsors
Cancer Hospital of Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Voluntary to participate in the clinical study, sign a written informed consent form, and able to comply with clinical visits and study-related procedures. 2. Age >=18 years old upon signing the informed consent form. 3. Have histologically and/or cytologically confirmed unresectable advanced solid tumour who are refractory to or intolerant of available standard-of-care therapy or have no effective standard treatment available. (1) Escalation module: preferred tumour types include cervix, ovary, endometrium, pancreatic, bladder, prostate, esophageal cancer, HNSCC, triple-negative breast cancer (TNBC), cholangiocarcinoma, and NSCLC. (2) Backfill module: patients with cervix cancer, pancreatic cancer, HNSCC, NSCLC, ovarian and endometrial cancer. 4. Applicable only to the dose expansion module: Archival or fresh biopsy tumor samples must demonstrate TF expression positivity [defined as protein expression >=1% by immunohistochemistry (IHC)]. 5. ECOG performance score of 0 or 1. 6. Life expectancy >= 3 months. 7. At least one measurable lesion per RECIST v1.1. 8. Adequate organ function defined as following: a) Hematological status: neutrophil count (ANC) >= 1.5×10^9/L, platelet count (PLT) >= 90×10^9/L, and hemoglobin (HGB) > 10.0 g/dL (no blood transfusion or hematopoietic stimulating factor therapy within 14 days before the evaluation). b) Coagulation function: international normalized ratio (INR) =1.2 (without anticoagulant therapy) and activated partial prothrombin time (APTT) = 60 mL/min. (calculated by the Cockcroft-Gault formula); however, subjects with CrCl = 50%; QTcF <=470 ms by Fridericia formula. 9. Eligible patients with fertility (male and female) must agree to use reliable contraceptive methods with their partners during the trial period and at least 3 months after the last IP administration; female patients of childbearing age must have a negative serum pregnancy test within 7 days before the first investigational drug administration. 10. Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.
Exclusion criteria
Exclusion criteria: The patient who meets any of the following criteria should be excluded from this study: 1. Chemotherapy, small-molecule targeted agents, or hormonal anticancer therapy within 2 weeks before the first dose of investigational product; OR biological anticancer therapy (macromolecular agents) within 4 weeks or 5 half-lives (whichever comes first) prior to the first dose. . 2. Known past or current coagulation defects leading to an increased risk of bleeding or any known bleeding diathesis. 3. History of Steven’s Johnson’s syndrome or Toxic Epidermal Necrolysis syndrome. 4. Known to be allergic to T320 for injection or any of its excipients, or patients with allergic constitution. 5. Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies. 6. Known history of non-infectious pneumonitis (NIP)/interstitial lung disease (ILD) requiring systemic steroids, active NIP/ILD, or other severe lung disease. 7. Presence of grade = 2 peripheral neuropathy. 8. Ongoing acute or chronic inflammatory skin disease. 9. Presence of ocular surface disease (i.e., confluent superficial keratitis, cornea epithelial defect, corneal ulcer, stromal opacity, etc) or history of conjunctivitis. 10. Presence of acute bacterial, viral or fungal infections. 11. Untreated, unstable or uncontrolled central nervous system (CNS) metastases, except for: a) No evidence of cerebral edema and no systemic steroids or anticonvulsants requirement at screening and follow-up MRI scan performed within 28 days prior to the first dose of the IMP showing no progression of treated lesion(s) and no new lesion(s) appearing. b) Untreated asymptomatic brain metastasis and no need of local/systematic therapy currently. 12. Any prior therapy with a conjugated or unconjugated auristatin derivative. 13. Patient requiring concurrent treatment of strong inhibitors or inducers of cytochrome P450 3A4 (Table 3) within 2 weeks prior to the first dose and during the study treatment. 14. Have previously received allogeneic hematopoietic stem cell transplantation or solid organ transplantation, or plan to receive allogeneic hematopoietic stem cell transplantation or solid organ transplantation during the study period. 15. History of or currently central nervous system (CNS) lymphoma or other central nervous system diseases. 16. Known to have any active infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). However, patients with the following conditions can be included in this study: a) Hepatitis B surface antigen (HBsAg) is negative; if HBsAg or HBcAb is positive, HBV-DNA (HBV deoxyribonucleic acid) < 1000 cps/mL. b) Hepatitis C virus antibody (HCV-Ab) is negative. 17. Toxicity except for alopecia and fatigue caused by previous anti-tumour therapy has not been alleviated to grade 1 or below (CTCAE v5.0). 18. History of other malignant tumor within 2 years before enrollment, except for skin basal cell carcinoma, skin squamous cell carcinoma, and carcinoma in situ that have undergone possible curative treatment and have not recurred within 5 years after the start of treatment. 19. Have received any other investigational drug product within 28 days or 5 halflives of the previous investigational drug (if required) before screening. 20. Have used live attenuated vaccines within 4 weeks before the first administration of dexamethasone or are expected to use live attenuated vaccines during the study period. 2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Type, incidence, and severity of adverse events (AEs), serious adverse events (SAEs);dose-limiting toxicity (DLT) events;physical examinations;laboratory examinations;12-lead electrocardiogram (ECG);vital signs;Maximum tolerated dose;Recommended phase 2 dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Anti-tumour activity according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 assessed by the investigator: best overall response (BOR);Anti-tumour activity according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 assessed by the investigator: overall response rate (ORR);Anti-tumour activity according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 assessed by the investigator: disease control rate (DCR);Anti-tumour activity according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 assessed by the investigator: progression-free survival (PFS).;Anti-tumour activity according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 assessed by the investigator: overall survival (OS, only apply to Backfill Module).;PK parameters of T320, total antibody and payload, including but not limited to: Tmax, Cmax, AUClast, AUCtau, T1/2, Cmax, ss, Cmin, ss, CLss, Vss, Rac,AUC, Rac,Cmax and DF, etc.;Incidence of anti-drug antibodies (ADA) of T320; | — |
Countries
China
Contacts
Public ContactLi Ning
Cancer Hospital of Chinese Academy of Medical Sciences
Outcome results
None listed