The purpose of the Phase 1/2a study is to evaluate the safety and tolerability of SNK01 in combination with trastuzumab or cetuximab in order to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D), and the preliminary efficacy for each combination regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Patient-specific ex vivo expanded autologous natural killer cells
HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody
Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Evaluated by the number of DLTs graded using NCI CTCAE v5.0.
Time frame: Up to 6 months
Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Evaluated by the number of DLTs graded using NCI CTCAE v5.0.
Time frame: Up to 6 months
Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.
Time frame: Up to 12 months
Phase 2a - To assess objective response rate (ORR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Defined by percentage of subjects with a best response of complete response (CR), partial response (PR) or stable disease (SD) by investigator assessment per RECIST 1.1.
Time frame: Up to 12 months
Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.
Time frame: Up to 12 months
Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Defined by the time of the date of first dose of study drug until confirmed disease progression based on investigator assessment per RECIST 1.1 or death from any cause, whichever comes first.
Time frame: Up to 12 months
Phase 2a - To assess the overall survival (OS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Defined as time from first dose of study drug to death due to any cause.
Time frame: Up to 24 months
Phase 2a - To assess the overall survival (OS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Defined as time from first dose of study drug to death due to any cause.
Time frame: Up to 24 months
Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Defined as duration of time from initial response (complete response \[CR\] or partial response \[PR\]) to first documentation of disease progression or death from any cause, whichever occurs first.
Time frame: Up to 12 months
Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Defined as duration of time from initial response (complete response \[CR\] or partial response \[PR\]) to first documentation of disease progression or death from any cause, whichever occurs first.
Time frame: Up to 12 months
Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Defined as proportion of subjects who achieve an overall tumor response (complete response \[CR\] or partial response \[PR\] or stable disease \[SD\]).
Time frame: Up to 12 months
Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Defined as proportion of subjects who achieve an overall tumor response (complete response \[CR\] or partial response \[PR\] or stable disease \[SD\]).
Time frame: Up to 12 months
Phase 2a - Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).
The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales \[physical, role, cognitive, emotional and social\], three symptom scales \[fatigue, pain and nausea/vomiting\] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms. All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
Time frame: Up to 12 months
Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30).
The EORTC QLQ-C30 questionnaire consists of 30 questions, 24 of which are grouped into nine multi-item scales (five functioning scales \[physical, role, cognitive, emotional and social\], three symptom scales \[fatigue, pain and nausea/vomiting\] and one global health status scale). The remaining six questions are single-item scales (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact) and are intended to assess symptoms. All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
Time frame: Up to 12 months
Phase 2a-Impact of SNK01 in combination with trastuzumab on quality of life in subjects with advanced HER2 cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).
The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
Time frame: Up to 12 months
Phase 2a - Impact of SNK01 in combination with cetuximab on quality of life in subjects with advanced EGFR cancers evaluated using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13).
The EORTC QLQ-LC13 is a supplementary lung-cancer specific questionnaire and is used in conjunction with the EORTC QLQ-C30 questionnaire. It is comprised of 13 questions, 3 of which are grouped into a multi-item scale to assess dyspnea and 10 of which are single-item scales assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the scales and single-item measures are scored on a scale from 0 to 100. A better state of the patient is denoted by a higher score for the functioning scales and global health status, while a worsening state of the patient is denoted by higher scores on the symptom and single-item scales.
Time frame: Up to 12 months
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