Phase I Study of KY-0118 in Subjects With Locally Advanced or Metastatic Solid Tumors

A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of KY-0118 in Subjects With Locally Advanced or Metastatic Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Neoplasms by Histologic Type
• Intervention / Treatment: Drug: KY-0118; Drug: KY-0118; Drug: KY-0118

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.

• Study Type: Interventional
• Enrollment (Estimated): 189
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: si li; Phone Number: 17879528905; Email: s.li@novatim-zj.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233030
      • Recruiting
      • The First Affiliated Hospital Bengbu Medical College
      • Contact: Huan Zhou; Email: zhouhuanbest@163.com
      • Principal Investigator: Huan Zhou, M.D.
  • Beijing
    • Beijing, Beijing, China, 100853
      • Recruiting
      • The Fifth Medical Center of the Chinese PLA General Hospital
      • Principal Investigator: Guanghai Dai, professor
      • Contact: Guanghai Dai, professor; Email: daigh60@sohu.com
      • Principal Investigator: Lijun Chen, M.D.
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: Yu Chen, M.D.; Email: 13859089836@139.com
      • Principal Investigator: Yu Chen, M.D.
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Recruiting
      • Hubei province tumor hospital
      • Contact: Xinjun Liang; Email: Doctorlxj@163.com
      • Principal Investigator: Liang Xinjun, Doctor
  • Shandong
    • Jinan, Shandong, China, 276600
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Benkang Shi, M.D.; Email: bkang68@sdu.edu.cn
      • Principal Investigator: Benkang Shi, M.D.
      • Principal Investigator: Shuwen Yu, M.D.
    • Liaocheng, Shandong, China, 252000
      • Recruiting
      • The Second People's Hospital of Liaocheng
      • Contact: Yanjun Wang, M.D.; Email: wangyanjun7809@163.com
      • Principal Investigator: Yanjun Wang, M.D.
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Cancer Hospital
      • Contact: Yehui Shi; Email: shiyehui@tom.com
      • Principal Investigator: Yehui Shi, M.D.
      • Principal Investigator: Zhanyu Pan, Master
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Province Tumor Hospital
      • Contact: Meiyu Fang, M.D.; Email: fangmy@zicc.org.cn
      • Principal Investigator: Meiyu Fang, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KY-0118	Drug: KY-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; Drug: KY-0118; KY-0118 is to be injected intravenously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs; Drug: KY-0118; KY-0118 is to be injected subcutaneously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs;
Experimental: Cohort1: KY-0118	Drug: KY-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; Drug: KY-0118; KY-0118 is to be injected intravenously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs; Drug: KY-0118; KY-0118 is to be injected subcutaneously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs;
Experimental: Cohort2: KY-0118	Drug: KY-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; Drug: KY-0118; KY-0118 is to be injected intravenously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs; Drug: KY-0118; KY-0118 is to be injected subcutaneously with a dose of dose1~dose5 weekly until disease progresses or unacceptable tolerability occurs;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose-limiting toxicity (DLT)		21 days during the first 3-week cycle
Adverse Event	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.	Up to 28 days post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Peak expansion	Up to 7 days post last dose
Ctrough	Trough concentration	Up to 7 days post last dose
Tmax	time to peak expansion	Up to 7 days post last dose
T1/2	Elimination half-life	Up to 7 days post last dose
AUC	Area under curve	Up to 7 days post last dose
CL	Clearance rate	Up to 7 days post last dose
Regulatory t cells（Tregs）	Levels of Tregs in peripheral blood at baseline and during administration;	Up to 7 days post last dose
CD4+ T lymphocyte count	Levels of CD8+ T lymphocyte count in peripheral blood at baseline and during administration;	Up to 7 days post last dose
CD8+ T lymphocyte count	Levels of CD8+ T lymphocyte count in peripheral blood at baseline and during administration;	Up to 7 days post last dose
NK cells count	Levels of NK cells count in peripheral blood at baseline and during administration;	Up to 7 days post last dose
IL-6	Levels of IL-6 in peripheral blood at baseline and during administration;	Up to 7 days post last dose
IFN-γ	Levels of IFN-γ in peripheral blood at baseline and during administration;	Up to 7 days post last dose
TNF-ɑ	Levels of TNF-ɑ in peripheral blood at baseline and during administration;	Up to 7 days post last dose
Granzyme B	Levels of Granzyme B in peripheral blood at baseline and during administration;	Up to 7 days post last dose
Perforin	Levels of perforin in peripheral blood at baseline and during administration;	Up to 7 days post last dose
Objective response rate (ORR)	To evaluate the preliminary antitumor activity of KY-0118	Up to 28 days post last dose
Progression-free survival (PFS)	To evaluate the preliminary antitumor activity of KY-0118	Up to 28 days post last dose
Duration of response(DOR)	To evaluate the preliminary antitumor activity of KY-0118	Up to 28 days post last dose
Disease control rate (DCR)	To evaluate the preliminary antitumor activity of KY-0118	Up to 28 days post last dose
The incidence of ADA of KY-0118	Each subject will be tested for anti-drug (KY-0118) antibody (ADA)	Up to 7 days post last dose
The incidence of NAb of KY-0118	Each subject with ADA-positive serum samples will continue to be tested for neutralizing antibodies (NAb)	Up to 7 days post last dose
PD-1 receptor occupancy rate		Up to 7 days post last dose
IL-2 receptor occupancy rate	IL-2 receptor occupancy of Nk cells, CD8+ T lymphocyte and CD4+T lymphocyte	Up to 7 days post last dose
Ki67 phenotype	Ki67 phenotype of Nk cells and CD8+T lymphocyte	Up to 7 days post last dose

Collaborators and Investigators

• Sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2022
• Primary Completion (Estimated): December 28, 2025
• Study Completion (Estimated): December 28, 2025

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 8, 2023
• First Posted (Actual): December 19, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type
• Other Study ID Numbers: KY-0118-ZJKY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No