Clinical trial NCT06175780: Phase I Study of KY-0118 in Subjects With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of KY-0118 in Subjects With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Neoplasms by Histologic Type
Lead sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-12-19
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patients with dose-limiting toxicity (DLT)
timeFrame: 21 days during the first 3-week cycle
measure: Adverse Event
timeFrame: Up to 28 days post last dose
Secondary outcomes:
measure: Cmax
timeFrame: Up to 7 days post last dose
measure: Ctrough
timeFrame: Up to 7 days post last dose
measure: Tmax
timeFrame: Up to 7 days post last dose
measure: T1/2
timeFrame: Up to 7 days post last dose
measure: AUC
timeFrame: Up to 7 days post last dose
measure: CL
timeFrame: Up to 7 days post last dose
measure: Regulatory t cells（Tregs）
timeFrame: Up to 7 days post last dose
measure: CD4+ T lymphocyte count
timeFrame: Up to 7 days post last dose
measure: CD8+ T lymphocyte count
timeFrame: Up to 7 days post last dose
measure: NK cells count
timeFrame: Up to 7 days post last dose
measure: IL-6
timeFrame: Up to 7 days post last dose
measure: IFN-γ
timeFrame: Up to 7 days post last dose
measure: TNF-ɑ
timeFrame: Up to 7 days post last dose
measure: Granzyme B
timeFrame: Up to 7 days post last dose
measure: Perforin
timeFrame: Up to 7 days post last dose
measure: Objective response rate (ORR)
timeFrame: Up to 28 days post last dose
measure: Progression-free survival (PFS)
timeFrame: Up to 28 days post last dose
measure: Duration of response(DOR)
timeFrame: Up to 28 days post last dose
measure: Disease control rate (DCR)
timeFrame: Up to 28 days post last dose
measure: The incidence of ADA of KY-0118
timeFrame: Up to 7 days post last dose
measure: The incidence of NAb of KY-0118
timeFrame: Up to 7 days post last dose
measure: PD-1 receptor occupancy rate
timeFrame: Up to 7 days post last dose
measure: IL-2 receptor occupancy rate
timeFrame: Up to 7 days post last dose
measure: Ki67 phenotype
timeFrame: Up to 7 days post last dose
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: The Fifth Medical Center of the Chinese PLA General Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Wuhan
country: China
facility: Hubei Province Tumor Hospital
state: Hubei
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Liaocheng
country: China
facility: The Second People's Hospital of Liaocheng
state: Shandong
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Hangzhou
country: China
facility: Zhejiang Province Tumor Hospital
state: Zhejiang
Study officials:
References: