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

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Hamilton E, O'Malley DM, O'Cearbhaill R, Cristea M, Fleming GF, Tariq B, Fong A, French D, Rossi M, Brickman D, Moore K

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.

PubMed ID

32513564 [ View in PubMed

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Abstract

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 (0.025-0.4mg/kg) every 3weeks (Q3W), utilizing a standard 3+3 design (dose-limiting toxicity [DLT] period: 21days). 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 0.3mg/kg and the SC-003 doses selected for the dose-expansion phase of the study were 0.3mg/kg and 0.2mg/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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Budigalimab	Programmed cell death protein 1	Protein	Humans	Unknown	Regulator	Details