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
- 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
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.
- 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
- 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
- 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.