This is an open label, first-in-human, phase 1, dose escalation study to determine the safety
including dose limiting toxicity (DLT) and maximal tolerated dose of the monoclonal antibody
NEO-201 in adults with solid tumors (cancer) which has not responded to standard treatments.
The experimental drug called NEO-201 (the "study drug") is a monoclonal antibody that is
being tested and is not approved for use in the United States by the FDA.
The primary purpose of this first in human targeted phase 1 open-label study with NEO-201 in
subjects with advanced solid tumors is to determine the safety of NEO-201 and select a dose
for phase 2 clinical trials.
NEO-201 will be given in four increasing doses to make sure it is safe. NEO-201 will start at
a low dose (1 mg/kg) and be increased 3 times (2, 4, 6 mg/kg) over the period of the study in
different groups of subjects. Subjects who enroll during the early stages of the study, will
receive a lower dose of NEO-201, those who enroll later, will receive a higher dose that may
be associated with more side effects.
Inclusion Criteria:
- Age: >/=18 years
- Diagnosis:
- Histologically or cytologically confirmed recurrent, locally advanced
unresectable or metastatic cancer confirmed by the Laboratory of Pathology, NCI.
- Must have progressed after (or been intolerant of) standard therapy known to
provide clinical benefit for respective tumor type and for which standard
curative options do not exist or are no longer effective or tolerable.
- Must have archived tissue (10 unstained slides or tissue block), or must have
tumor which can be safely biopsied percutaneously and be willing to undergo a
tumor biopsy.
- Must have colorectal cancer, pancreatic cancer, adenocarcinoma of the lung,
squamous cell lung cancer, breast cancer, and mucinous and signet cell ovarian
cancer (cancer types in which tumor samples (> 50%) historically stain positive
for NEO-201 expression).
- Measurable disease (by RECIST)
- ECOG </=2; or Karnofsky performance status of 50%
- Laboratory Function: (within 21 days of the first dose of study drug)
- Hemoglobin > 9 g/dL, or on stable doses (hematocrit stable within 1 gram and dose
stable for one month) of erythropoietin or similar medication.
- Absolute neutrophil count (ANC) >/=1,500/mm3.
- Platelets >/=100,000/mm3.
- Total bilirubin </= 2.0 mg/dL
- ALT and AST </= 3 times the ULN, or, if the subject has liver metastases, </= 5
times the ULN.
- Creatinine </= 1.5 mg/dL or creatinine clearance > 40 mL/min/1.73 m2 for subjects
with creatinine levels above institutional normal
- Voluntary written informed consent before performance of any study-related procedure
that is not part of normal medical care.
- Prior Therapy:
- At least 14 days must have elapsed since treatment with oral tyrosine kinase
inhibitors, or until toxicities associated with TKI therapy have resolved.
- At least 21 days must have elapsed since treatment with previous monoclonal
antibodies, or until toxicities associated with mAb therapy have resolved.
- At least 4 weeks must have elapsed since any chemotherapeutic agents at the time
of enrollment (or 6 weeks for regimens containing BCNU or mitomycin C).
- At least 2 weeks must have elapsed since any systemic corticosteroids at the time
of enrollment
- At least 42 days after the completion of any type of immunotherapy, e.g. tumor
vaccines.
- XRT: At least 7 days after local palliative XRT (small port)
- Must have recovered from any acute toxicity related to prior therapy, except for
alopecia. Toxicity should be ≤ grade 1, or ≤ grade 2 for peripheral neuropathy, or
returned to baseline.
- Expected to be able to remain on a study protocol for at least 8 weeks.
- Females either post-menopausal, surgically sterilized, or willing to use acceptable
methods of birth control for the duration of the study.
Males must agree to use adequate contraception prior to the study, for the duration of
study participation, and 2 weeks after completion of NEO-201 administration.
Exclusion Criteria:
- History of disseminated or uncontrolled brain metastases or central nervous system
disease. Brain metastases will be considered controlled if SD on two consecutive brain
MRIs, performed at least 2 months apart, and subject is without seizures.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to NEO-201 or other agents used in this study.
- Any major surgery within 14 days of enrollment.
- Receiving any other investigational agents.
- No archival tissue available and a lesion(s) that cannot be safely biopsied via
percutaneous route, or is unwilling to undergo biopsy.
- Has an uncontrolled concomitant illness including, but not limited to, ongoing or
active infection, uncontrolled diabetes mellitus, symptomatic congestive heart
failure, unstable angina pectoris, hypokalemia, family history of Long QT Syndrome or
presence of cardiac arrhythmia.
- HIV-positive subjects on combination antiretroviral therapy are ineligible because of
the unknown potential for pharmacokinetic interactions with NEO-201. In addition,
these subjects are at increased risk of lethal infections which could complicate the
toxicity assessment of this study. Appropriate studies will be undertaken in subjects
receiving combination antiretroviral therapy when indicated.
- Subject has other serious medical illness, including a second malignancy, or
psychiatric illness that could, in the Investigator's opinion, potentially interfere
with the completion of treatment according to this protocol.
- Pregnant women are excluded from this study because the potential for teratogenic or
abortifacient effects due to NEO-201 is unknown. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with NEO-201, breastfeeding should be discontinued if the mother is treated
with NEO-201.
- Subjects with marked baselined prolongation of QT/QTc interval (e.g. 2 ECGs on
separate dates demonstrating QTc interval > 450 ms).
- Use of concomitant medications associated with a high risk of DtP and prolongation of
QT/QTc interval
