This is a Phase 1/2 prospective, open label, multi-institution, dose escalation clinical trial to test
safety and efficacy of a therapeutic monoclonal antibody, nPC-1C directed against histologically
confirmed metastatic small bowel, appendiceal or colorectal cancer and metastatic or recurrent adenocarcinoma of the pancreas inthose tumors that stain at least 20% positive for the tumor antigenic target. Subjects who meet these
criteria and all other eligibility criteria will be enrolled on this study.
Twenty-six patients have been enrolled on this study with nPC-1C (neo-101). Thirteen received neo-101 in the phase 1 portion, establishing a MTD of 1.5 mg/kg. This MTD was expanded in a Phase 2a portion of the study and an additional 11 patients received nPC-1C (neo-101) without additional DLT. Three (3) were nonevaluable for the Phase 2a endpoints, and 2 enrolled subjects were not treated.
The study agent nPC-1C (neo-102), a new formulation, was manufactured and 12 patients were enrolled in a 3+3 dose escalation design at 1.5 mg/kg, 2 mg/kg, 3 mg/kg and 4 mg/kg dose levels. upon determining the MTD or highest dose evaluated if no MTD is found, additional patients will be enrolled into two cohorts based on histology: cohort 1) recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas oR 2) metastatic colorectal, (including small bowel or appendiceal cancer) or colorectal adenocarcinoma, to evaluate the impact on overall survival (oS). nPC-1C (neo-102) will be administered intravenously every two weeks for 4 doses. Six weeks of dosing (4 doses of nPC-1C) plus 2 weeks for evaluation will be considered one course (57 days). Patients who receive at least 2 (two) doses of nPC-1C will be considered evaluable for response in the Phase 2 portion of the study.
at the conclusion of the first course, if a subject has not experienced a dose limiting toxicity (DLT),
if restaging scans show stable disease (SD) or clinical response (PR or CR) per ReCiST criteria, and
the subject chooses to proceed, they may be treated additional 8 courses of nPC-1C (neo-102) until off treatment/off study criteria (Section 3.7 in the protocol) are met.
Eligible subjects must meet the following inclusion criteria:
- AGE: >= 18 years of age.
o Histologically confirmed recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after or were intolerant of front line chemotherapy regimen (at least one regimen), OR
o Histologically confirmed metastatic small bowel, colorectal adenocarcinoma or appendiceal cancer who have progressed after or were intolerant of at least 2 standard chemotherapy regimens.
- Tumor sections must stain >= 20% positive for NPC-1C antibody/antigen target as determined by the Department of Pathology at the respective institution or a central laboratory (Duke University Medical Center).
- MEASURABLE/EVALUABLE DISEASE: Measurable disease (by RECIST v1.1)
- PERFORMANCE STATUS: Karnofsky performance status of >= 50% (See Appendix 3)
- LABORATORY FUNCTION:
Screening laboratory data within 21 days of the first dose of study drug:
o Hemoglobin > 8.5 g/dL, or on stable doses (hematocrit stable within 1 gram and dose stable for one month) of erythropoietin or similar medication.
o Absolute neutrophil count (ANC) >=1,500/mm3.
o Platelets >= 50,000/mm3.
o Total bilirubin <= 2.0
o ALT and AST <= 3 times the ULN, or, if the patient has liver metastases, <= 5 times the ULN.
o Creatinine <= 1.5 mg/dL or creatinine clearnace > 40 mL/min?1.73 m2 for patients
with creatinine levels above institutional normal, as calculated by the Cockcroft Gault
- INFORMED CONSENT: Voluntary written informed consent before performance of any study-related procedure that is not part of normal medical care.
- Subject is expected to be able to remain on a study protocol for at least 8 weeks.
- BIRTH CONTROL: Female subject is post-menopausal, surgically sterilized, or willing to use acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, or condom with spermicide, or abstinence) for the duration of the study. Male subject agrees to use an acceptable barrier method for contraception during the study.