Clinical Trials /

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

NCT04464967

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Preliminary Efficacy of SNK01 in Combination With Trastuzumab or Cetuximab in Subjects With Advanced HER2 or EGFR Cancers
  • Official Title: A Phase 1/2a, Open-Label, Multi-Center Study Evaluating the Safety and Anti-Tumor Activity of Ex Vivo Expanded, Autologous Natural Killer Cells (SNK01) in Combination With Trastuzumab or Cetuximab in Subjects With Advanced/Metastatic HER2- or EGFR-Expressing Cancers

Clinical Trial IDs

  • ORG STUDY ID: SNK01-102
  • NCT ID: NCT04464967

Conditions

  • 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

Interventions

DrugSynonymsArms
SNK01Phase 1, Cohort 1
TrastuzumabHerceptinPhase 1, Cohort 1
CetuximabErbituxPhase 1, Cohort 3

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1, Cohort 1ExperimentalSNK01 (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)
  • SNK01
  • Trastuzumab
Phase 1, Cohort 2ExperimentalSNK01 (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)
  • SNK01
  • Trastuzumab
Phase 1, Cohort 3ExperimentalSNK01 (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)
  • SNK01
  • Cetuximab
Phase 1, Cohort 4ExperimentalSNK01 (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)
  • SNK01
  • Cetuximab
Phase 2, Expansion Cohort 1ExperimentalSNK01 (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)
  • SNK01
  • Trastuzumab
Phase 2, Expansion Cohort 2ExperimentalSNK01 (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)
  • SNK01
  • Cetuximab

Eligibility Criteria

        Inclusion Criteria:

          -  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:

             a. Hematological (without growth factor or transfusion support within 14 days prior to
             screening): i. Absolute neutrophil count ≥ 1.5 × 109/L (1,500/mm3) ii. Platelet count
             ≥ 75 × 109/L (75,000/mm3) iii. Hemoglobin ≥ 9.0 g/dL iv. Prothrombin
             time-international normalized ratio and partial thromboplastin time ≤ 1.5 × upper
             limit normal (ULN)

             b. Renal: i. Calculated creatinine clearance (CrCl) or 24 hour urine CrCl > 50
             mL/minute (Note: Cockcroft-Gault formula will be used to calculate CrCl)

             c. Hepatic: i. Total bilirubin ≤ 1.5 × ULN; for subjects with documented/suspected
             Gilbert's disease, bilirubin ≤ 3 × ULN ii. Aspartate aminotransferase (AST) and
             alanine aminotransferase (ALT) ≤ 2.5 × ULN (AST/ALT can be up to 5 × ULN in the
             presence of liver metastasis, but cannot be associated with concurrent elevated
             bilirubin)

             d. Serum electrolytes: i. Potassium, sodium, magnesium, and calcium (corrected for
             serum albumin) ≤ Grade 1 or within the institutional ranges of normal. If clinically
             appropriate, electrolytes may be corrected and values re-assessed prior to enrollment.

          -  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.

        Exclusion Criteria:

          -  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:

               1. Myocardial infarction within 3 months,

               2. Congestive heart failure of the New York Heart Association (NYHA) class 3 or 4,
                  or patients with history of congestive heart failure NYHA class 3 or 4 in the
                  past, unless a screening LVEF assessment ≥ 45%,

               3. Prolonged QT interval defined as screening corrected QT interval (QTc) > 470 ms
                  (Fridericia correction formula),

               4. History of clinically significant ventricular arrhythmia (e.g., ventricular
                  tachycardia, ventricular fibrillation),

               5. History of Mobitz II 2nd degree or 3rd degree heart block without a permanent
                  pacemaker in place,

               6. Hypotension (systolic blood pressure [BP] < 86 mmHg) or bradycardia with a heart
                  rate < 50 bpm,

               7. Uncontrolled hypertension as indicated by a resting systolic BP > 170 mmHg or
                  diastolic BP > 105 mmHg despite an optimal treatment,

          -  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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 - To determine recommended Phase 2 dose (RP2D) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Time Frame:Up to 6 months
Safety Issue:
Description:Evaluated by the number of DLTs graded using NCI CTCAE v5.0.

Secondary Outcome Measures

Measure:Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 2a - To assess the overall survival (OS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as time from first dose of study drug to death due to any cause.
Measure:Phase 2a - To assess the overall survival (OS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as time from first dose of study drug to death due to any cause.
Measure:Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 2a - To assess the duration of response (DOR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure:Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.
Time Frame:Up to 12 months
Safety Issue:
Description:Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).
Measure:Phase 2a - To assess the clinical benefit rate (CBR) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.
Time Frame:Up to 12 months
Safety Issue:
Description:Defined as proportion of subjects who achieve an overall tumor response (complete response [CR] or partial response [PR] or stable disease [SD]).
Measure: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).
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure: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).
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure: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).
Time Frame:Up to 12 months
Safety Issue:
Description: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.
Measure: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).
Time Frame:Up to 12 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NKMax America, Inc.

Trial Keywords

  • Natural killer cell
  • NK cell
  • Expanded natural killer cell
  • Immunotherapy
  • Cancer
  • Metastatic cancer
  • Advanced cancer
  • Recurrent cancer
  • HER2 Positive
  • HER2+
  • HER2
  • EGFR Positive
  • EGFR+
  • EGFR
  • Solid tumor
  • Breast Cancer
  • Gastric Cancer
  • Esophageal Cancer
  • Ovarian Cancer
  • Endometrium Cancer
  • Bladder Cancer
  • Pancreatic Cancer
  • Colorectal Cancer
  • Non Small Cell Lung Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Triple Negative Breast Cancer
  • Cervical Cancer
  • Sarcoma

Last Updated

July 6, 2020