Patient case: 73-year-old female with Pancreatic ductal adenocarcinoma. Genetic variant: ERBB3. Other conditions: Whipple, FNA.

Clinical trial: Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

Summary: The primary objective is to evaluate the safety and tolerability of IMMU-132 as a single agent administered in 3-week treatment cycles for up to 8 cycles, in previously treated patients with advanced epithelial cancer.The secondary objectives are to obtain initial data concerning pharmacokinetics, immunogenicity, and efficacy with this dosing regimen. IMMU-132 targets the TROP-2 antigen which is expressed on a variety of cancers. The antibody, RS7, is attached to SN38, which is the active metabolite of irinotecan. This is planned as a multi-center study. In Phase II, up to 130 patients (assessable) in triple-negative breast cancer, up to 100 patients (assessable) in non-small cell and small-cell lung cancer and up to 50 patients (assessable) per other cancer types included in the protocol will be studied at the 10 mg/kg dose.

Detailed description: This is a Phase I/II, open-label study of IMMU-132 in previously treated patients with advanced epithelial cancers, including ovarian, breast, prostate (hormone refractory), lung (non-small cell and small cell), head & neck (squamous cell), esophageal, gastric, colorectal, pancreatic, hepatocellular, renal (clear cell), endometrial, cervical, urothelial, thyroid cancers and glioblastoma multiforme. Patients receive IMMU-132 administered once-weekly for the first 2 weeks of 3-week treatment cycles. Patients may receive up to a maximum total of 8 cycles (16 doses), but patients with a partial response or stable disease at that time, or patients who had achieved an objective response but relapsed after discontinuing treatment, may continue to be treated based on physician discretion. Treatment will continue until unacceptable toxicity or progression of disease. Both safety and efficacy will be assessed.

Eligibility: Inclusion Criteria:
  -  Male or female patients, >18 years of age, able to understand and give written informed consent.
  -  Histologically or cytologically confirmed epithelial cancer of one of the following types:
  -  Colorectal
  -  Gastric adenocarcinoma
  -  Esophageal cancer
  -  Hepatocellular carcinoma
  -  Non-small cell lung cancer
  -  Small cell lung cancer
  -  Ovarian epithelial cancer
  -  Cervical Cancer
  -  Endometrial Cancer
  -  Breast cancer
  -  Hormone-refractory prostate cancer
  -  Pancreatic ductal adenocarcinoma
  -  Head and neck cancers- squamous cell
  -  Renal cell cancer (clear cell)
  -  Urothelial cancers
  -  Glioblastoma multiforme
  -  Follicular thyroid cancer
  (Note: Confirmation of Trop-2 expression by immunohistology or other means is not required, but the Sponsor will request tissue specimens from archived materials for determination of Trop-2 expression.)
  -  Stage IV (metastatic) disease.
  -  Refractory to or relapsed after at least one prior standard therapeutic regimen (Appendix 1 lists approved or standard chemotherapeutic agents for each cancer type. Patients who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving IMMU-132 are available prior to consenting to participate in this trial.)
  -  Adequate performance status (ECOG 0 or 1)
  -  Expected survival > 6 months.
  -  Measurable disease by CT or MRI.
  -  At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia).
  -  At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted).
  -  Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3).
  -  Adequate renal and hepatic function (creatinine ≤ 2.0 x IULN, bilirubin ≤ 1.5 IULN, AST and ALT ≤ 3.0 x IULN or 5 x IULN if know liver metastases).
  -  Otherwise, all toxicity at study entry < Grade 1.
  Exclusion Criteria:
  -•Women who are pregnant or lactating.
  -  Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.
  -  Patients with Gilbert's disease.
  -  Patients with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (>20 mg prednisone or equivalent) for at least 4 weeks.
  -  Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). Patients with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
  -  Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.
  -  Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval.
  -  Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive.
  -  Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.
  -  Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.
  -  Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.
  -  Infection requiring intravenous antibiotic use within 1 week.
  -  history of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan,
  -  Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.

Relevance to patient case: not relevant