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

Phase 1

Recruiting

• Conditions: Neoplasms by Histologic Type; Neoplasms
• Interventions: Drug: KY-0118

• Registration Number: NCT06175780
• Lead Sponsor: Novatim Immune Therapeutics (Zhejiang) Co., Ltd.

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.

Study Timeline

• Study Start: 2022-12-28
• Study First Submitted: 2023-11-29
• Status Verified: 2023-12
• Study First Submitted QC: 2023-12-08
• Study First Posted: 2023-12-19
• Last Update Submitted: 2023-12-19
• Last Update Posted: 2023-12-26
• Primary Completion: 2025-12-28
• Study Completion: 2025-12-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 189

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
KY-0118	KY-0118	-
Cohort2: KY-0118	KY-0118	-
Cohort1: KY-0118	KY-0118	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
PD-1 receptor occupancy rate	Up to 7 days post last dose
Ctrough	Up to 7 days post last dose	Trough concentration
CL	Up to 7 days post last dose	Clearance rate
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
Cmax	Up to 7 days post last dose	Peak expansion
Tmax	Up to 7 days post last dose	time to peak expansion
IL-6	Up to 7 days post last dose	Levels of IL-6 in peripheral blood at baseline and during administration;
Ki67 phenotype	Up to 7 days post last dose	Ki67 phenotype of Nk cells and CD8+T lymphocyte
T1/2	Up to 7 days post last dose	Elimination half-life
AUC	Up to 7 days post last dose	Area under curve
NK cells count	Up to 7 days post last dose	Levels of NK cells count 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;
Progression-free survival (PFS)	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)
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 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)
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;
IFN-γ	Up to 7 days post last dose	Levels of IFN-γ 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

Trial Locations

Locations (8)

The Fifth Medical Center of the Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Tianjin Cancer Hospital; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital Bengbu Medical College; 🇨🇳 Bengbu, Anhui, China

The Second People's Hospital of Liaocheng; 🇨🇳 Liaocheng, Shandong, China

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China

Hubei Province Tumor Hospital; 🇨🇳 Wuhan, Hubei, China

Zhejiang Province Tumor Hospital; 🇨🇳 Hangzhou, Zhejiang, China

Fujian Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China