Neoplasms, Neoplasms by Histologic Type
Conditions
Brief summary
This dose escalation and dose expansion study is to evaluate and characterize the tolerability, safety, pharmacokinetics and efficacy profile of single agent KY-0118 in Locally Advanced or Metastatic Solid Tumor Patients.
Detailed description
For Phase Ia It aims to evaluate the safety, tolerability, pharmacokinetic characteristics, pharmacodynamic effect, immunogenicity in subjects with locally advanced or metastatic solid tumor patients , and determine the appropriate dose of KY-0118. For Phase Ib it aims is to further evaluate the efficacy, safety, tolerability, pharmacokinetic properties, pharmacodynamic effects and immunogenicity of KY-0118 with appropriate dose groups (approximately 3-5 dose groups) in different Administration manner.
Interventions
DRUGKY-0118
KY-0118 is to be injected intravenously with a dose of 0.3μg/kg, 1μg/kg, 3μg/kg, 6μg/kg, 12μg/kg, 24μg/kg, 36μg/kg, 48μg/kg or 64μg/kg until disease progresses or unacceptable tolerability occurs;
Sponsors
Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years old and ≤75 years old, male or female; 2. Subjects with a documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; progression or are intolerant to existing standard therapy or subjects without standard therapy; 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1；Expected survival time≥ 12 weeks; 4. At least one measurable lesion per RECIST 1.1 (without local treatment or progress after local treatment); 5. Adequate organ function; 6. Toxicity from prior anticancer therapy recovered to ≤ grade 1 prior to the first dose of study drugs; 7. Signed informed consent and willingly adherence to the experimental treatment protocol and visit plan.
Exclusion criteria
1. Specific anti-tumor treatment prior to use of study treatment; 2. Immunosuppressants or systemic hormone therapy were being used and were not discontinued within 2 weeks prior to enrollment; 3. IL-2 treatment within 6 months prior to the first dose of study drugs; 4. Any immune related adverse events (irAE) that have occurred during previous immunotherapy medication, with a grade of ≥ 3 or leading to termination of immunotherapy; 5. Primary Central Nervous System (CNS) Malignant Tumors or Active CNS Metastasis with Local Treatment Failure; 6. Any severe and/or uncontrolled diseases, including but not limited to: uncontrolled hypertension or pulmonary hypertension or unstable angina; Chronic heart failure; Valve disease; Severe arrhythmia; Had myocardial infarction or bypass or stent surgery within 6 months before screening; 7. History of arteriovenous thromboembolism within 6 months prior to screening； 8. Moderate or severe respiratory distress at rest due to advanced malignant tumors or their complications or severe primary lung diseases；or a current need for continuous oxygen therapy, or a current history of interstitial lung disease (ILD) or pneumonia, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm, etc. ; 9. Uncontrolled bleeding or known tendency to bleed; Patients with chronic Crohn's disease and ulcerative colitis;Patients with hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndrome;Patients with a history of intestinal perforation and fistula, but not cured after surgical treatment;Esophagogastric varices; 10. Third space effusion that cannot be controlled by puncture and drainage treatment and require repeated drainage or have obvious symptoms; 11. Patients who require extensive fluid replacement assessed by investigators; 12. Active hepatitis B or active hepatitis C; 13. Active infectious process; 14. A history of immunodeficiency; 15. Autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disease, multiple sclerosis, etc.; 16. Patients with allergic constitution, or known to have a history of allergy to IL-2 or PD-1/PD-L1 drugs or any of their components, or known to have a history of severe allergic reactions to fusion proteins; 17. History of other malignancies within 5 years prior to screening; 18. Surgery (other than diagnostic biopsy) within 4 weeks prior to screening or planned to have surgery during the study period; 19. Had received live vaccine within 4 weeks before the first dose or planned to receive live vaccine during the trial; 20. History of neurological or psychiatric disorders, such as epilepsy, dementia, altered mental status, and poor compliance; 21. History of alcohol or drug abuse within the last 1 year; 22. Women who are pregnant or breastfeeding. Patients unwilling to use a highly effective method of contraception during the study period and for 6 months after receiving the trial drug; 23. Attended other study within 4 weeks prior to screening; 24. Other conditions deemed unsuitable for inclusion by the investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with dose-limiting toxicity (DLT) | 21 days during the first 3-week cycle | — |
| Adverse Event | Up to 28 days post last dose | Incidence of untoward medical occurrences (adverse event = AE) in a participant who received study drug. Adverse events will be evaluated by dosing cohort and recorded according to NCI CTCAE Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Up to 7 days post last dose | Peak expansion |
| Ctrough | Up to 7 days post last dose | Trough concentration |
| Tmax | Up to 7 days post last dose | time to peak expansion |
| T1/2 | Up to 7 days post last dose | Elimination half-life |
| AUC | Up to 7 days post last dose | Area under curve |
| CL | Up to 7 days post last dose | Clearance rate |
| Regulatory t cells（Tregs） | Up to 7 days post last dose | Levels of Tregs in peripheral blood at baseline and during administration; |
| CD4+ T lymphocyte count | Up to 7 days post last dose | Levels of CD8+ T lymphocyte count in peripheral blood at baseline and during administration; |
| CD8+ T lymphocyte count | Up to 7 days post last dose | Levels of CD8+ T lymphocyte count in peripheral blood at baseline and during administration; |
| NK cells count | Up to 7 days post last dose | Levels of NK cells count in peripheral blood at baseline and during administration; |
| IL-6 | Up to 7 days post last dose | Levels of IL-6 in peripheral blood at baseline and during administration; |
| IFN-γ | Up to 7 days post last dose | Levels of IFN-γ in peripheral blood at baseline and during administration; |
| TNF-ɑ | Up to 7 days post last dose | Levels of TNF-ɑ in peripheral blood at baseline and during administration; |
| Granzyme B | Up to 7 days post last dose | Levels of Granzyme B in peripheral blood at baseline and during administration; |
| Perforin | Up to 7 days post last dose | Levels of perforin in peripheral blood at baseline and during administration; |
| Objective response rate (ORR) | Up to 28 days post last dose | To evaluate the preliminary antitumor activity of KY-0118 |
| Progression-free survival (PFS) | Up to 28 days post last dose | To evaluate the preliminary antitumor activity of KY-0118 |
| Duration of response(DOR) | Up to 28 days post last dose | To evaluate the preliminary antitumor activity of KY-0118 |
| Disease control rate (DCR) | Up to 28 days post last dose | To evaluate the preliminary antitumor activity of KY-0118 |
| The incidence of ADA of KY-0118 | Up to 7 days post last dose | Each subject will be tested for anti-drug (KY-0118) antibody (ADA) |
| The incidence of NAb of KY-0118 | Up to 7 days post last dose | Each subject with ADA-positive serum samples will continue to be tested for neutralizing antibodies (NAb) |
| PD-1 receptor occupancy rate | Up to 7 days post last dose | — |
| IL-2 receptor occupancy rate | Up to 7 days post last dose | IL-2 receptor occupancy of Nk cells, CD8+ T lymphocyte and CD4+T lymphocyte |
| Ki67 phenotype | Up to 7 days post last dose | Ki67 phenotype of Nk cells and CD8+T lymphocyte |
Countries
China
Contacts
Primary Contactsi li
Outcome results
None listed