Tamrintamab pamozirine (SC-003) in patients with platinum-resistant/refractory ovarian cancer: Findings of a phase 1 study

Gynecol Oncol. 2020 Sep;158(3):640-645. doi: 10.1016/j.ygyno.2020.05.038. Epub 2020 Jun 6.


Objective: Epithelial ovarian carcinoma (EOC) is diagnosed at advanced stage in the majority of women and, despite being initially chemosensitive, eventually recurs and develops resistance to known therapies. SC-003 is a pyrrolobenzodiazepine-based antibody-drug conjugate targeting dipeptidase 3 (DPEP3), a membrane-bound dipeptidase associated with tumor-initiating cells in patient-derived EOC xenograft models. This first-in-human phase 1a/1b study evaluated the safety/tolerability, pharmacokinetics, and preliminary antitumor activity of SC-003 alone or in combination with budigalimab (formerly ABBV-181), an antibody targeting PD-1, in patients with platinum-resistant/refractory EOC (NCT02539719).

Methods: Patients received SC-003 at 1 of 6 dose levels (0.025-0.4 mg/kg) every 3 weeks (Q3W), utilizing a standard 3 + 3 design (dose-limiting toxicity [DLT] period: 21 days). Patients with DPEP3-positive tumors were enrolled in the dose-expansion phase of the study and treated with SC-003 monotherapy or in combination with budigalimab.

Results: Seventy-four patients (n = 29, dose escalation; n = 45, dose expansion; n = 3 budigalimab combination) were enrolled and received ≥1 dose of study drug. One DLT occurred (grade 3 ileus) but was considered unrelated to study drug. The MTD for the Q3W schedule was 0.3 mg/kg and the SC-003 doses selected for the dose-expansion phase of the study were 0.3 mg/kg and 0.2 mg/kg. The most common treatment-emergent adverse events were fatigue, nausea, decreased appetite, pleural effusion, abdominal pain, and peripheral edema. The overall response rate was low (4%), and responses were not durable. Post-hoc examination of antitumor activity suggested a higher response rate in patients with higher DPEP3 expression.

Conclusions: SC-003 lacked the requisite safety profile and antitumor activity to warrant further development.

Keywords: Antibody-drug conjugate; Dipeptidase 3; Epithelial ovarian carcinoma; Pyrrolobenzodiazepine; SC-003; Tumor-initiating cells.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Benzodiazepines / administration & dosage*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / pharmacokinetics
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Dipeptidases / metabolism
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / adverse effects
  • Immunoconjugates / pharmacokinetics
  • Middle Aged
  • Molecular Targeted Therapy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Pyrroles / pharmacokinetics


  • Immunoconjugates
  • Pyrroles
  • pyrrolo(2,1-c)(1,4)benzodiazepine
  • Benzodiazepines
  • DPEP3 protein, human
  • Dipeptidases

Associated data

  • ClinicalTrials.gov/NCT02539719