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LK101 Combined With PD-1 or PD-L1 Monoclonal Antibody in the Treatment of Lung Cancer

Primary Purpose

Advanced Lung Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LK101 injection (personlized neoantigen pulsed DC vaccine )
Pembrolizumab
Durvalumab
Sponsored by
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Lung Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: signed informed consent; ≥18years, male or female; cohort1: Histologically/cytologically confirmed locally advanced or metastastic Non-small lung carcinoma (NSCLC), and received systemic treatment for recurrence/metastasis ≤3 lines; cohort2: Histologically/cytologically confirmed extensive small-cell lung carcinoma (ES-SCLC); Both cohorts required patients progressed/recurrenced after anti-PD-1/PD-L1treatment; Life expectancy of more than 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1; At least one measurable lesion according to RECIST 1.1; The sequencing of tumor were qualified; According to the invistigators' judgment, venous vascular conditions can meet the needs of apheresis; For adequate organ function, the patients need to meet the following laboratory indexes: hematologic functions(No blood transfusion or treatment with blood components and without granulocyte colony stimulating factor in the past 14 days.): the absolute value of neutrophils (ANC) ≥ 1.5x109/L; the platelet count was ≥ 90x109/L; the hemoglobin > 9g/dL; Hepatic functions: Total bilirubin ≤ 1.5 × normal upper limit (ULN); patients with liver metastasis allow ≤ 3 × ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (patients with liver metastasis allow ALT or AST ≤ 5 × ULN); renal Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 50ml; patients with urinary protein ≥ + + and confirmed 24-hour urinary protein quantity > 1.0g; Coagulation function is good, defined as international standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is beyond the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; FBG of patients without type 2 diabetes ≤ 126 mg/dL or ≤ 7.0 mmol/L, and that of patients with type 2 diabetes ≤ 167 mg/dL or ≤ 9.3 mmol/L; Or glycosylated hemoglobin (HbA1c) ≤8%; If there is a risk of pregnancy, all patient (male or female) are required to take appropriate methods for contraception during the study until the 6th month post the last administration of study drug; Well compliance, cooperate with follow-up; Exclusion Criteria: History of hypersensitivity reaction to any vaccine and/or anti-PD-1/PD-L1 formulation ingredients; Or have had a previous severe allergic reaction to other monoclonal antibodies; Subjects who had previously discontinued anti-PD-1 /PD-L1 therapy due to "infusion reaction" or immune-related AE; 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 reasearch drugs or device therapy; Received radiotherapy within 2 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); The tumor compresses the surrounding important organs or the superior vena cava, or invades the mediastinal great blood vessels, the heart, .etc; Patients who have recewived allogeneic hematopoietic stem cell transplantation or organ transplantation; A history of medical conditions that may trigger seizures (requiring treatment with antiepileptic medications); Patients who have active brain metastases or cancerous meningitis. Patients with treated brain metastases are eligible if they have been treated with brain metastases, and clinically stable for atleast 3 months, no evidence of disease progression 4 weeks before. All neurological symptoms had recovered, and off steroids at least 7 days prior to screening; Diaginosied or suspected of having an active autoimmune disease; patients with poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage, or received pleural effusion or ascites treatment within the past 3 months; 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 disease; Patients with interstitial pneumonia, except those inactive and do not require hormone therapy disease; Patients diagnosed with active infections that are poorly controlled by systemic treatment; 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; Skin diseases, such as psoriasis, may prevent intradermal vaccines from reaching the target area; Other conditions regimented at investigators' discretion.

Sites / Locations

  • Cancer hospital Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LK101 injection combined with pembrolizumab

LK101 injection combined with durvalumab

Arm Description

patients with locally advanced or metastastic (stage IIIB-IV) NSCLC and received ≤3 lines systemtic therapy. eligible subjects will receive LK101 injection and pembrolizumab treatment.

patients with extensive SCLC who failed with at least first-line standard therapy. eligible subjects will receive LK101 injection and durvalumab treatment.

Outcomes

Primary Outcome Measures

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.
AE
incidence and severity of adverse events
irAE
incidence and severity of immune-related adverse events
SAE
incidence and severity of serious adverse events

Secondary Outcome Measures

ORR
Objective Response Rate (ORR)according to mRECIST 1.1 standard
DoR
Duration of remission
DCR
Disease Control Rate
TTR
Time to remission
TTP
Time to progression
PFS
Progression Free Survival
OS
Overall Survival
Immune response evaluation
T cell response, cytokines, etc.

Full Information

First Posted
May 6, 2023
Last Updated
May 23, 2023
Sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT05886439
Brief Title
LK101 Combined With PD-1 or PD-L1 Monoclonal Antibody in the Treatment of Lung Cancer
Official Title
A Study of LK101 Combined With PD-1 or PD-L1 Monoclonal Antibody in the Treatment of Lung Cancer to Evaluate the Safety, Tolerability and Preliminary Efficacy
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2023 (Actual)
Primary Completion Date
July 30, 2025 (Anticipated)
Study Completion Date
December 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a open lable, single-center phase Ib/IIa study for patients with local advanced or metastastic NSCLC or ES-SCLC, who failed with previous anti-PD-1/PD-L1 therapy. The aim is to observe and evaluate the safety, tolerability and efficacy of LK101 injection combined with pembrolizumab or durvalumab respectively in the incurable NSCLC and SCLC.
Detailed Description
This study is designed to evaluate the safety and efficacy of LK101 injection combined with pembrolizumab or durvalumab, which devided into 2 cohorts: cohort 1: patients with locally advanced or metastastic (stage IIIB-IV) NSCLC who has progressed/relapsed after anti-PD-1/PD-L1 therapy. eligible subjects will receive LK101 injection and pembrolizumab treatment. cohort 2: patients with extensive SCLC who failed with at least first-line standard therapy with PD-L1. eligible subjects will receive LK101 injection and durvalumab treatment. LK101 will be administered in a prime-boost schedule of 4 priming vaccination followed by 3 booster vaccinations. For the priming phase: LK101 administered once a week at Days 1, 8, 15, 22. For the booster phase: total of 3 vaccinations will be given, Q3W from the end of priming dose. Treatment can be continued according to the investigator's evaluation, subsequent treatment is administered Q6W. Patients will receive a combination of pembrolizumab(200mg IV) Q3W and durvalumab (1500mg IV) Q3W in NSCLC and SCLC,respectively, until disease progression (PD), intolerable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Lung Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LK101 injection combined with pembrolizumab
Arm Type
Experimental
Arm Description
patients with locally advanced or metastastic (stage IIIB-IV) NSCLC and received ≤3 lines systemtic therapy. eligible subjects will receive LK101 injection and pembrolizumab treatment.
Arm Title
LK101 injection combined with durvalumab
Arm Type
Experimental
Arm Description
patients with extensive SCLC who failed with at least first-line standard therapy. eligible subjects will receive LK101 injection and durvalumab treatment.
Intervention Type
Drug
Intervention Name(s)
LK101 injection (personlized neoantigen pulsed DC vaccine )
Intervention Description
LK101 will be administered in a prime-boost schedule of 4 priming vaccination followed by 3 booster vaccinations.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Patients will receive pembrolizumab(200mg IV) Q3W until disease progression (PD), intolerable toxicity.
Intervention Type
Drug
Intervention Name(s)
Durvalumab
Intervention Description
Patients will receive durvalumab (1500mg IV) Q3W until disease progression (PD), intolerable toxicity.
Primary Outcome Measure Information:
Title
DLT
Description
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.
Time Frame
Continuously throughout the study until 90 days after Termination of the treatment
Title
AE
Description
incidence and severity of adverse events
Time Frame
Continuously throughout the study until 90 days after Termination of the treatment
Title
irAE
Description
incidence and severity of immune-related adverse events
Time Frame
Continuously throughout the study until 90 days after Termination of the treatment
Title
SAE
Description
incidence and severity of serious adverse events
Time Frame
Continuously throughout the study until 90 days after Termination of the treatment
Secondary Outcome Measure Information:
Title
ORR
Description
Objective Response Rate (ORR)according to mRECIST 1.1 standard
Time Frame
accessed up to 24 months from baseline
Title
DoR
Description
Duration of remission
Time Frame
24 months
Title
DCR
Description
Disease Control Rate
Time Frame
24 months
Title
TTR
Description
Time to remission
Time Frame
24 months
Title
TTP
Description
Time to progression
Time Frame
24 months
Title
PFS
Description
Progression Free Survival
Time Frame
24 months
Title
OS
Description
Overall Survival
Time Frame
24 months
Title
Immune response evaluation
Description
T cell response, cytokines, etc.
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Tumor immune microenvironment before and after treatment
Description
CD8+T cell, PD-1, PD-L1, etc.
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: signed informed consent; ≥18years, male or female; cohort1: Histologically/cytologically confirmed locally advanced or metastastic Non-small lung carcinoma (NSCLC), and received systemic treatment for recurrence/metastasis ≤3 lines; cohort2: Histologically/cytologically confirmed extensive small-cell lung carcinoma (ES-SCLC); Both cohorts required patients progressed/recurrenced after anti-PD-1/PD-L1treatment; Life expectancy of more than 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1; At least one measurable lesion according to RECIST 1.1; The sequencing of tumor were qualified; According to the invistigators' judgment, venous vascular conditions can meet the needs of apheresis; For adequate organ function, the patients need to meet the following laboratory indexes: hematologic functions(No blood transfusion or treatment with blood components and without granulocyte colony stimulating factor in the past 14 days.): the absolute value of neutrophils (ANC) ≥ 1.5x109/L; the platelet count was ≥ 90x109/L; the hemoglobin > 9g/dL; Hepatic functions: Total bilirubin ≤ 1.5 × normal upper limit (ULN); patients with liver metastasis allow ≤ 3 × ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (patients with liver metastasis allow ALT or AST ≤ 5 × ULN); renal Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥ 50ml; patients with urinary protein ≥ + + and confirmed 24-hour urinary protein quantity > 1.0g; Coagulation function is good, defined as international standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is beyond the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; FBG of patients without type 2 diabetes ≤ 126 mg/dL or ≤ 7.0 mmol/L, and that of patients with type 2 diabetes ≤ 167 mg/dL or ≤ 9.3 mmol/L; Or glycosylated hemoglobin (HbA1c) ≤8%; If there is a risk of pregnancy, all patient (male or female) are required to take appropriate methods for contraception during the study until the 6th month post the last administration of study drug; Well compliance, cooperate with follow-up; Exclusion Criteria: History of hypersensitivity reaction to any vaccine and/or anti-PD-1/PD-L1 formulation ingredients; Or have had a previous severe allergic reaction to other monoclonal antibodies; Subjects who had previously discontinued anti-PD-1 /PD-L1 therapy due to "infusion reaction" or immune-related AE; 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 reasearch drugs or device therapy; Received radiotherapy within 2 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); The tumor compresses the surrounding important organs or the superior vena cava, or invades the mediastinal great blood vessels, the heart, .etc; Patients who have recewived allogeneic hematopoietic stem cell transplantation or organ transplantation; A history of medical conditions that may trigger seizures (requiring treatment with antiepileptic medications); Patients who have active brain metastases or cancerous meningitis. Patients with treated brain metastases are eligible if they have been treated with brain metastases, and clinically stable for atleast 3 months, no evidence of disease progression 4 weeks before. All neurological symptoms had recovered, and off steroids at least 7 days prior to screening; Diaginosied or suspected of having an active autoimmune disease; patients with poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage, or received pleural effusion or ascites treatment within the past 3 months; 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 disease; Patients with interstitial pneumonia, except those inactive and do not require hormone therapy disease; Patients diagnosed with active infections that are poorly controlled by systemic treatment; 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; Skin diseases, such as psoriasis, may prevent intradermal vaccines from reaching the target area; Other conditions regimented at investigators' discretion.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jie Wang, MD,PhD
Phone
13910704669
Email
jiewang_hr@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jie Wang, MD,PhD
Organizational Affiliation
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer hospital Chinese Academy of Medical Sciences
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Wang, MD
Phone
87788524
Ext
010
Email
jiewang_hr@sina.com

12. IPD Sharing Statement

Plan to Share IPD
No

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LK101 Combined With PD-1 or PD-L1 Monoclonal Antibody in the Treatment of Lung Cancer

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