Safety, Tolerability, and Immunogenicity of LK101 Alone in Participants With Incurable Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is an open-labeled, single-center phase I study in patients with incurable advanced solid tumors, who failed with all previous standard therapy. The aim is to observe and evaluate the safety, tolerability, and immunogenicity of LK101 injection.

Detailed Description
-----------------
This study is designed to evaluate the safety, tolerability, and immunogenicity of the dose escalation of LK101. We used the traditional 3+3 dose escalation design, Subjects who have been pathologically diagnosed with advanced solid tumors and defined as failing all previous standard therapy. LK101 will be administered in a prime-boost schedule of 4 priming vaccination followed by 3 booster vaccinations. The dose escalation will be conducted in a sequential manner, enrolled patients were initially placed in cohort 1, in which the priming phase is administered at 2-week intervals. And then followed the next cohort 2, where the priming phase is administered at 1-week intervals. Decisions with regard to dose escalation to the next dose level will be made jointly by the investigators and the sponsor. AE data was collected until the 21 days following the last prime dose. safety and immunogenicity will also be used to inform the final dose and schedule. A minimum of 6 patients will be treated at the MTD/RP2D.

Official Title
-----------------
A Phase I Study of LK101 Monotherapy in Participants With Advanced Solid Tumors to Evaluate the Safety, Tolerability, and Immunogenicity

Conditions
-----------------
Advanced Solid Tumor

Intervention / Treatment
-----------------
* Drug: LK101 injection
* Drug: LK101 injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: signed informed consent. Age 18-75. life expectancy ≥3 months. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors, unresponsive to standard treatment or for whom no standard treatment is available or appropriate. The sequencing of the tumor was qualified. Subject must have measurable diseases as per RECIST v1.1 criteria. According to the investigator's judgment, venous vascular conditions can meet the needs of apheresis. Adequate bone marrow, renal, and hepatic at screening and at Baseline. Exclusion Criteria: Patients who have received therapeutic tumor vaccine products (including peptide vaccine, mRNA vaccine, DC vaccine, etc.). Diagnosis of malignant diseases other than study disease within 5 years before screening (except for malignant tumors that can be expected to recover after treatment). Patients received systemic antitumor treatment within 2 weeks before the apheresis, or receive research drugs or device therapy. Received radiotherapy within 4 weeks prior to screening. Toxicity caused by previous treatment did not recover to CTCAE (version 5.0) Grade 1 or below (except hair loss and peripheral neuropathy). Patients who have active brain metastases or cancerous meningitis. History of significant cardiovascular and cerebrovascular disease occurred in the 6 months prior to screening, Any of the following cardiac criteria: Mean resting corrected QT interval (QTc) > 470 ms; Left ventricular ejection fraction (LVEF) ≤ 50%; American New York heart association (NYHA) heart function ≥ 2 or higher; serious arrhythmia; poorly controlled hypertension; other serious heart diseases; Patients with interstitial pneumonia, except those inactive and do not require hormone therapy disease; Any of the following test results are positive: human immunodeficiency virus (HIV) antibody, treponema pallidum antibody, hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA and novel coronavirus nucleic acid. Active tuberculosis (TB) during screening. Treatment with systemic steroids or other immunosuppressive agents within 14 days prior to screening; Vaccination within 4 weeks prior to screening. Major injuries and/or surgery =< 4 weeks prior to screening. Persons with a history of psychotropic substance abuse and inability to abstain or with a history of mental disorders. Pregnant or lactating women. Other conditions are regimented at the investigators' discretion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2weeks-intervals prime dose procedure<br>LK101 will be administered in a prime-boost schedule, which is 4 priming vaccination as 2-weeks-intervals followed by 3 booster vaccinations | Drug: LK101 injection<br>* LK101 administrated Q2W as the prime dose, and Q3W in the boost phase<br>|
| Experimental: 1weeks-intervals prime dose procedure<br>LK101 will be administered in a prime-boost schedule, which is 4 priming vaccination as 1-weeks-intervals followed by 3 booster vaccinations | Drug: LK101 injection<br>* LK101 administrated QW as the prime dose, and Q3W in the boost phase<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | incidence of Dose limited toxicity(DLT),incidence and severity of adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs); Clinically significant abnormal changes in laboratory tests and other tests. | Continuously throughout the study until 90 days after Termination of the treatment | 
| AE | incidence and severity of adverse events | Continuously throughout the study until 90 days after Termination of the treatment | 
| irAE | incidence and severity of immune-related adverse events | Continuously throughout the study until 90 days after Termination of the treatment | 
| SAE | incidence and severity of serious adverse events | Continuously throughout the study until 90 days after Termination of the treatment | 
| RP2D | Recommended phase 2 immune procedure | 21 days after the last prime dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunogenicity | neoantigen specific T cell response by ELISpot measurement | 24 months | 
| ORR | Objective Response Rate (ORR)according to mRECIST 1.1 standard | 24 months | 
| DoR | Duration of remission | 24 months | 
| DCR | Disease Control Rate | 24 months | 
| TTR | Time to remission | 24 months | 
| TTP | Time to progression | 24 months | 
| PFS | Progression Free Survival | 24 months | 
| OS | Overall Survival | 24 months |