| Eligibility |
Inclusion Criteria:
1. Male or female and age =18 years
2. Histologically confirmed locally advanced and/or metastatic solid organ tumor
including but not limited to the following histology: Non-Small Cell Lung cancer
(NSCLC), Gastrointestinal cancer (GI), Breast cancer (BC), Gynecological cancers
(GYN). Date of histology should be not older than 18 months from the start of the
screening procedures. Additionally 30 patients will be enrolled in 4 expansion
cohorts: 1) refractory metastatic Colorectal cancer (mCRC) patients who have failed
prior treatment with standard chemotherapeutics and both anti-VEGF and anti-EGFR
antibodies; 2) patients with recurrent and/or metastatic Head and Neck cancers, who
have failed prior treatment with a checkpoint inhibitor and at least one line of
chemotherapy as appropriate depending on the histology and platinum-elegibility;
salivary gland tumors can be enrolled in this cohort after failure of at least one
line of chemotherapy; 3) refractory metastatic NonSmall Cell Lung cancer (NSCLC)
patients who have failed all standard treatment options including chemotherapy,
tyrosine kinase inhibitors and immunotherapy as appropriate depending on the histology
and mutational status, 4) refractory metastatic Breast cancer (BC) patients who have
failed all standard treatment options including chemotherapy, hormone therapy and
anti-human epidermal growth factor receptor 2 [HER2] treatment as appropriate
depending on the histology.
3. Patients are required to have a positive EGFR IHC expression (=25% of tumor cells) as
assessed by local laboratory. This condition will not be required anymore in the
additional 30 patients of the expansion cohorts
4. Measurable disease according to RECIST 1.1. At least 1 lesion, not previously
irradiated, that can be accurately measured at baseline as =10 mm in the longest
diameter (except lymph nodes which must have a short axis =15 mm) with computed
tomography (CT) or magnetic resonance imaging (MRI) and that is suitable for accurate
repeated measurements as per RECIST 1.1 guidelines
5. Failure of standard therapy or non-availability of standard therapy (patients must
have received at least one line of chemotherapy and further standard therapy is not an
option at study entry)
6. Prior treatment with any anti-EGFR agent should be completed at least 4 months before
start of treatment. This condition will no longer be required in the 30 additional
patients of the expansion cohorts.
7. Toxicities, except for alopecia and Grade 2 neuropathy, should be not greater than
Grade 1 before start of treatment according to the National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI-CTCAE [v. 4.0])
8. Eastern Cooperative Oncology Group (ECOG) Performance Status =1 and estimated life
expectancy of =3 months
9. Adequate organ function as evidenced by the following:
1. Bone marrow function: hemoglobin =90 g/L; white blood cell (WBC) count =3.0 x
109/L; absolute neutrophil count (ANC) =1.0 x 109/L; platelet count =75 x 109/L
2. Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) =2.5 x upper limit of normal (ULN) (=5 x ULN if hepatic metastases
present); bilirubin =1.5 x ULN; alkaline phosphatase =5.0 x ULN
3. Renal function: creatinine <1.5 x ULN
4. Cardiologic function: LVEF fraction = 50% assessed by radionuclide angiography
(MUGA scan) or Echocardiography
10. Patients of both genders with procreative potential must use effective contraception
while enrolled in the study and for at least 6 months (for women) or 16 weeks (for
men) after the last study drug infusion
11. Written informed consent obtained prior to conducting any study specific procedures
Exclusion Criteria:
1. First 20 patients: Known activating EGFR mutation. This exclusion criterion will no
more apply for the 30 additional patients of the expansion cohorts.
2. Involvement in the planning and/or conduct of the study (applies to both Glycotope
staff and/or staff at the study site)
3. Concurrent enrolment in another clinical study, unless it is an observational
(noninterventional) clinical study or during the follow-up period of an interventional
study
4. Patients institutionalized by official means or court order.
5. Chemotherapy, radiation, or any other anti-cancer therapies, including any
investigational agent, within 4 weeks prior start of study treatment
6. Concurrent anti-tumor therapy or concurrent immunotherapy
7. Current or prior use of immunosuppressive medication within 28 days before the first
dose of study drug. The following are exceptions to this criterion:
1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection)
2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or its equivalent
3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
8. Major surgery within 4 weeks prior to entering the study and/or incomplete recovery
from surgery or planned major surgery
9. Primary or secondary immune deficiency requiring treatment. Active or prior documented
autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g.,
colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis],
systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome
[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet only
10. Clinically active infections >Grade 2 according to the Common Terminology Criteria for
Adverse Events (NCI-CTCAE v. 4.0)
11. Patients with known severe allergy or hypersensitivity to other human monoclonal
antibodies or who experienced infusion related reactions or other severe toxicity that
required permanent interruption of a prior antibody treatment.
12. Active infection including tuberculosis (clinical evaluation that includes clinical
history, physical examination and radiographic findings, and TB testing in line with
local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients
with a past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA.
13. History of another primary malignancy except for: a. Malignancy treated with curative
intent and with no known active disease =3 years before the first dose of IMP and of
low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or
lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ
without evidence of disease d. Localized prostate cancer
14. Uncontrolled medical condition considered as high risk for treatment with an
investigational drug including unstable diabetes mellitus, vena-cava-syndrome, or
chronic symptomatic respiratory disease
15. Clinical signs of brain metastasis or leptomeningeal involvement
16. Symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or
IV), unstable angina pectoris or MI within 6 months prior to enrollment, significant
cardiac arrhythmia, history of stroke, or transient ischemic attack within 1 year
17. History of seizures, encephalitis, or multiple sclerosis
18. Active drug abuse or chronic alcoholism
19. Pregnant or breastfeeding
20. Known sensitivity to any component of the drugs used
21. Contraindication to the premedication (H1 and/or H2 receptor antagonists and steroids)
or commercial anti-EGFR used in this study
22. Legal incompetence, limited legal competence, or detainment in an institution for
official or legal reasons
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