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

NCT04464967 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: SNK01-102
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

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

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• Phase 2a - To assess the progression-free survival (PFS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.

  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.

  Up to 12 months

• Phase 2a - To assess the overall survival (OS) of SNK01 in combination with trastuzumab in subjects with advanced HER2 cancers.

  Up to 24 months

• Phase 2a - To assess the overall survival (OS) of SNK01 in combination with cetuximab in subjects with advanced EGFR cancers.

  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.

  Up to 12 months

Study Arms (6)

Phase 1, Cohort 1

EXPERIMENTAL

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; Drug: Trastuzumab

Phase 1, Cohort 2

EXPERIMENTAL

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; Drug: Trastuzumab

Phase 1, Cohort 3

EXPERIMENTAL

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; Drug: Cetuximab

Phase 1, Cohort 4

EXPERIMENTAL

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; Drug: Cetuximab

Phase 2, Expansion Cohort 1

EXPERIMENTAL

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; Drug: Trastuzumab

Phase 2, Expansion Cohort 2

EXPERIMENTAL

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; Drug: Cetuximab

Interventions

SNK01 BIOLOGICAL

Patient-specific ex vivo expanded autologous natural killer cells

Phase 1, Cohort 1; Phase 1, Cohort 2; Phase 1, Cohort 3; Phase 1, Cohort 4; Phase 2, Expansion Cohort 1; Phase 2, Expansion Cohort 2

Trastuzumab DRUG

HER2 receptor antagonistic, humanized immunoglobulin G subclass 1 (IgG1) monoclonal antibody

Also known as: Herceptin

Phase 1, Cohort 1; Phase 1, Cohort 2; Phase 2, Expansion Cohort 1

Cetuximab DRUG

EGFR antagonist, chimeric immunoglobulin G subclass 1 (IgG1) monoclonal antibody

Also known as: Erbitux

Phase 1, Cohort 3; Phase 1, Cohort 4; Phase 2, Expansion Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Myocardial infarction within 3 months,
• 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%,
• Prolonged QT interval defined as screening corrected QT interval (QTc) \> 470 ms (Fridericia correction formula),

Sponsors & Collaborators

• NKGen Biotech, Inc.: lead

MeSH Terms

Conditions

Neoplasm Metastasis; Esophageal Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Urinary Bladder Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms; Uterine Cervical Neoplasms; Sarcoma; Neoplasms; Recurrence; Breast Neoplasms; Stomach Neoplasms

Interventions

Trastuzumab; Cetuximab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Pancreatic Diseases; Intestinal Neoplasms; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Cervical Diseases; Neoplasms, Connective and Soft Tissue; Disease Attributes; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Y. Song, MD

  NKGen Biotech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 9, 2020
• Study Start: March 1, 2021
• Primary Completion: August 1, 2022
• Study Completion: February 1, 2023
• Last Updated: May 12, 2021

Record last verified: 2021-05