An Open-label, Multi-center Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of T320, an Anti-Tissue Factor Antibody-Drug Conjugate, in Patients With Advanced Solid Tumor
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Nanolattix Biotechnology Co., Ltd.
- Enrollment
- 150
- Primary Endpoint
- Dose-limiting toxicity (DLT)
Overview
Brief Summary
This is a first-in-human, non-randomized, open-label, multi-center, phase I study in patients with advanced solid tumor to evaluate the safety and tolerability, PK, immunogenicity, and preliminary anti-tumour activity of T320. This study consists of a dose escalation module and a backfill module. The trial process for each subject in both escalation and backfill module includes a screening period (28 days before the first T320 administration), a treatment period (from the first T320 administration to the end of reatment), a safety follow-up period (28 days after EOT/early withdrawal) and a progression follow-up period (every 12 weeks from safety follow-up visit). Patients will receive T320 administration once every 2 weeks (Q2W) and 28 days are set as one treatment cycle.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntary to participate in the clinical study, sign a written informed consent form, and able to comply with clinical visits and study-related procedures.
- •Age ≥18 years old upon signing the informed consent form.
- •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.
- •Escalation module: preferred tumour types include cervix, ovary, endometrium, pancreatic, bladder, prostate, esophageal cancer, HNSCC, triple-negative breast cancer (TNBC), cholangiocarcinoma, and NSCLC. Backfill module: patients with cervix cancer, pancreatic cancer, HNSCC, NSCLC, ovarian and endometrial cancer.
- •ECOG performance score of 0 \~
- •Life expectancy ≥ 3 months.
- •At least one measurable lesion per RECIST v1.
- •Adequate organ function defined as following: a) Hematological status: neutrophil count (ANC) ≥ 1.5×109/L, platelet count (PLT) ≥ 90×109/L, and hemoglobin (HGB) \> 9.0 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) ≤1.25×ULN. c) Liver function: total bilirubin (TBIL) ≤ 1.5×ULN or ≤ 3×ULN in case of Gilbert's syndrome; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5×ULN, if there is liver metastasis, ALT and AST ≤ 5×ULN. d) Renal function: creatinine clearance (Cockcroft-Gault) ≥ 60 mL/min. e) Cardiac function: left ventricular ejection fraction (LVEF) ≥ 50%; QTcF≤470 ms by Fridericia formula.
- •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.
- •Availability of tumour tissue sample (either an archival specimen or a fresh biopsy material) at screening.
Exclusion Criteria
- •Any anti-cancer therapy including chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment.
- •Known past or current coagulation defects leading to an increased risk of bleeding or any known bleeding diathesis.
- •History of Steven's Johnson's syndrome or Toxic Epidermal Necrolysis syndrome.
- •Known to be allergic to T320 for injection or any of its excipients, or patients with allergic constitution.
- •Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies.
- •Known history of non-infectious pneumonitis (NIP)/interstitial lung disease (ILD) requiring systemic steroids, active NIP/ILD, or other severe lung disease.
- •Presence of grade ≥ 2 peripheral neuropathy.
- •Ongoing acute or chronic inflammatory skin disease.
- •Presence of ocular surface disease (i.e., confluent superficial keratitis, cornea epithelial defect, corneal ulcer, stromal opacity, etc) or history of conjunctivitis.
- •Presence of acute bacterial, viral or fungal infections.
Arms & Interventions
T320 for Injection
Intervention: T320 for Injection (Biological)
Outcomes
Primary Outcomes
Dose-limiting toxicity (DLT)
Time Frame: Q2W: Up to 28 days
Adverse event (AE) assessed by CTCAE v5.0
Time Frame: The period of AE collection starts after the subject receives the T320, until 28+7 days after the EOT/early withdrawal or before the patient starts another anti-tumour treatment (whichever occurs first).
Serious adverse events (SAEs)
Time Frame: From the signing of the informed consent to 28±7 days after the EOT/early withdrawal or before the patient starts another anti-tumour treatment (whichever occurs first), through study completion, an average of 1 year.
maximum tolerated dose (MTD)
Time Frame: Q2W: Up to 28 days
recommended Phase 2 dose (RP2D)
Time Frame: The RP2D will be finally selected by pooling and evaluating all available efficacy, PK, safety and tolerability data in dose escalation and backfill module, through study completion, an average of 1 year.
RP2D as administered once every 2 weeks (Q2W) and 28 days are set as one treatment cycle.
heart rate
Time Frame: through study completion, an average of 1 year
electrocardiogram (ECG) QT Interval
Time Frame: through study completion, an average of 1 year
Secondary Outcomes
- Best overall response (BOR)(through study completion, an average of 1 year)
- Overall response rate (ORR)(through study completion, an average of 1 year)
- Disease control rate (DCR)(through study completion, an average of 1 year)
- Progression-free survival (PFS)(through study completion, an average of 1 year)
- Maximum observed serum concentration (Cmax)(through study completion, an average of 1 year)
- Anti-drug antibody (ADA)(through study completion, an average of 1 year)
- Time to reach Cmax (Tmax)(through study completion, an average of 1 year)
- Area under concentration-time profiles from zero to last timepoint of measurable concentration (AUClast)(through study completion, an average of 1 year)
- Area under concentration-time profiles during a dose interval (AUCtau)(through study completion, an average of 1 year)
- Terminal half-life (T1/2)(through study completion, an average of 1 year)
- Steady state maximum concentration (Cmax, ss)(through study completion, an average of 1 year)
- Steady state minimum concentration (Cmin, ss)(through study completion, an average of 1 year)
- Clearance at steady state (CLss)(through study completion, an average of 1 year)
- Volume of distribution at steady state (Vss)(through study completion, an average of 1 year)
- Ratio of AUC (Rac,AUC)(through study completion, an average of 1 year)
- Ratio of Cmax (Rac,Cmax)(through study completion, an average of 1 year)
- Degree of fluctuation (DF)(through study completion, an average of 1 year)