Safety And Preliminary Efficacy Of SNK01 In Combination With Trastuzumab Or Cetuximab In Subjects With Advanced HER2 Or EGFR Cancers

Study Overview

Safety and Preliminary Efficacy of SNK01 in Combination With Trastuzumab or Cetuximab in Subjects With Advanced HER2 or EGFR Cancers

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.

N/A

Advanced Solid Tumor
Metastatic Cancer
HER2-positive Breast Cancer
HER2-positive Gastric Cancer
HER-2 Protein Overexpression
Esophageal Cancer
Ovarian Cancer
Endometrium Cancer
Bladder Cancer
Pancreatic Cancer
Colorectal Cancer
Non Small Cell Lung Cancer
EGF-R Positive Non-Small Cell Lung Cancer
Head and Neck Squamous Cell Carcinoma
Triple Negative Breast Cancer
Cervical Cancer
Sarcoma

BIOLOGICAL: SNK01
DRUG: Trastuzumab
DRUG: Cetuximab

SNK01-102

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-07-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2021-05-10
First Submitted that Met QC Criteria 2020-07-06	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2021-05-12
First Posted (ACTUAL) 2020-07-09	Results First Posted N/A	Last Verified 2021-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1, Cohort 1 SNK01 (low dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Trastuzumab HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EXPERIMENTAL: Phase 1, Cohort 2 SNK01 (high dose) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Trastuzumab HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EXPERIMENTAL: Phase 1, Cohort 3 SNK01 (low dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Cetuximab EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EXPERIMENTAL: Phase 1, Cohort 4 SNK01 (high dose) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Cetuximab EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EXPERIMENTAL: Phase 2, Expansion Cohort 1 SNK01 (TBD RP2D) administered once every three weeks in combination with trastuzumab (loading dose of 8 mg/kg on Cycle 1, Day 1, followed by a 6 mg/kg on Cycle 2, Day 1 once every three weeks)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Trastuzumab HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody
EXPERIMENTAL: Phase 2, Expansion Cohort 2 SNK01 (TBD RP2D) administered once every week in combination with cetuximab (loading dose of 400 mg/m2 on Cycle 1, Day 1, followed by a 250 mg/m2 on Cycle 2, Day 1 once every week)	BIOLOGICAL: SNK01 Patient-specific ex vivo expanded autologous natural killer cells DRUG: Cetuximab EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody

Primary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	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.	Up to 12 months

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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]).	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]).	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.	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.	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.	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.	Up to 12 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.
Males and females ages 18 to 75 years, inclusive.
Diagnosed with any documented histologically confirmed HER2 or EGFR-positive malignancy whose disease is confirmed to be metastatic and/or unresectable for which all treatment options considered to be standard of care therapy appropriate for the specific tumor type have been received and are no longer effective (i.e., subjects are refractory to standard of care therapies).
One or more tumors measurable per RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
At least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational).
At least 2 weeks since prior palliative radiotherapy.
Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
Adequate organ function as determined by:

Women of childbearing potential who are not abstinent and intend to be sexually active with a nonsterilized male partner must be willing to use an adequate method of contraception from 28 days prior to the first study drug(s) administration and 120 days following last day of the last administration of last study drug(s) discontinued; acceptable methods include hormonal contraception (oral contraceptives - as long as on stable dose, patch, implant, and injection), intrauterine devices, or double barrier methods (e.g., vaginal diaphragm/vaginal sponge plus condom, or condom plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be surgically sterile for at least 1 year after last menstrual period.
Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide from 28 days prior to the first study drug(s) administration throughout the total duration of the treatment period and 120 days after the last dose of last study drug(s) discontinued. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male subjects should refrain from sperm donation throughout this period.

Pregnant and/or lactating females. Women of childbearing potential must have negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days prior to receiving the first administration of the study drug(s) and a negative urine pregnancy test on Day 1 before first administration of the study drug(s). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required.
Life expectancy of less than three months.
Currently being treated with immunotherapy or received immunotherapy during the treatment regimen immediately prior to participation in this study.
Untreated for HER2- or EGFR-positive metastatic and/or unresectable malignancy OR have refused an available standard of care therapy appropriate for the specific tumor type for any reason other than for a known sensitivity, toxicity, or contraindication.
For EGFR-positive patients, first line cetuximab treatment stopped due to allergic response.
For EGFR-positive patients, superior vena cava syndrome contra-indicating hydration.
Untreated or symptomatic central nervous system (CNS) metastases. Note: Subjects with asymptomatic treated CNS metastases are eligible provided they have been clinically stable and not requiring steroid treatment for at least 4 weeks.
No resolution of specific toxicities related to any prior anti-cancer therapy to Grade ≤1 according to the NCI-CTCAE v.5.0 (except lymphopenia and alopecia).
Active peripheral or motor neuropathy of any CTCAE grade and due to any cause.
Known hypersensitivity or allergy or contraindication to at least one of the study drugs.
In case of previous chemotherapy, wash out period of less than 5 half-lives of treatment before study entry.
Clinically significant cardiovascular disease including:

Major surgery within 4 weeks prior first study drug administration or already planned during the study.
Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug(s). (Note: Subjects participating in an observational study are an exception to this criterion and may qualify for the study with Sponsor approval)
Any pulmonary, thyroid, renal, hepatic severe/uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol.
Active uncontrolled viral, fungal or bacterial infection requiring systematic therapy within 14 days of Day 1.
High fever or any active or unresolved infection.
Known history of testing positive for human immunodeficiency virus (HIV), and/or positive test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C antibody result with detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic infection.
Autoimmune disease requiring therapy; immunodeficiency, or any disease process requiring immunosuppressive therapy.
A serious nonmalignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent illness, etc.) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Any other condition that, in the opinion of the Investigator, would prohibit the subject from participating in the study.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Paul Y. Song, MD, NKGen Biotech, Inc.

Publications

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