Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

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 until unacceptable progression or toxicity, in previously treated patients with advanced epithelial cancer. In Phase II, the primary objective is the evaluation of the safety and efficacy of IMMU-132 administered in 3-week treatment cycles at a dose selected in Phase I, while the secondary objectives include pharmacokinetics and immunogenicity.

Detailed description: This is a Phase I/II, open-label study of IMMU-132 in previously treated patients with advanced epithelial cancers. Patients receive IMMU-132 administered once-weekly for the first 2 weeks of 3-week treatment cycles. Treatment cycles 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:
  -  Gastric adenocarcinoma (GC)
  -  Esophageal cancer (EC)
  -  Hepatocellular carcinoma (HCC)
  -  Non-small-cell lung cancer (NSCLC)
  -  Small-cell lung cancer (SCLC)
  -  Epithelial ovarian cancer (EOC)
  -  Cervical Cancer
  -  Endometrial Cancer
  -  Triple-negative breast cancer [With Amendment 10, these patients need to have unequivocal TNBC histology (ER-/PR-/HER2-) per ASCO/CAP guidelines, based on most recently analyzed biopsy, and must have had at least 2 prior therapies for metastatic disease, including prior taxane (any setting). Chemotherapy, biological or targeted or immunotherapy agents will count as qualifying prior therapies, but not hormonal or anti-HER2 agents (either given prior to achieving triple negative status or for any other reason).]
  -  Non-triple-negative breast cancer
  -  Follicular thyroid cancer
  -  Glioblastoma multiforme (GBM)
  -  Hormone-refractory prostate cancer (HRPC)
  -  Head and neck cancers- squamous cell (SCCHN)
  -  Renal cell cancer (clear cell) (RCC)
  -  Urothelial 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 (except for patients with GBM).
  -  Refractory to or relapsed after at least one prior standard therapeutic regimen
  -  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