A Phase 1a/1b Dose Escalation and Expansion Study of SC-003 as a Single-Agent and in Combination With ABBV-181 in Subjects With Platinum-Resistant/ Refractory Ovarian Cancer

Stemcentrx0 sites74 target enrollmentAugust 2015

ConditionsOvarian Cancer

InterventionsSC-003 SC-003 in combination with ABBV-181

DrugsSC-003 SC-003 in combination with ABBV-181

Overview

Phase: Phase 1
Intervention: SC-003
Conditions: Ovarian Cancer
Sponsor: Stemcentrx
Enrollment: 74
Primary Endpoint: Adverse Events
Status: Terminated
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

This is a Phase 1a/1b study of SC-003 as a single agent and in combination with ABBV-181 in patients with platinum-resistant/refractory ovarian cancer. SC-003 is an antibody-drug conjugate (ADC) comprised of a monoclonal antibody linked to a potent chemotherapy. ABBV-181 is a humanized, recombinant, mAb that binds to cell surface expressed programmed cell death 1 (PD-1).

Detailed Description

Phase 1a is a dose escalation study in patients with histologically/cytologically confirmed ovarian cancer that are platinum-resistant or refractory. Phase 1b is an expansion study where patients will be enrolled and treated at recommended dose and schedule based on the Phase 1a.

Registry

clinicaltrials.gov

Start Date

August 2015

End Date

January 2, 2019

Last Updated

7 years ago

Study Type

Interventional

Study Design

Sequential

Sex

Female

Investigators

Sponsor

Stemcentrx

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically confirmed ovarian epithelial cancer
•Evidence of progressive disease (PD) on or within 6 months of a platinum (cisplatin or carboplatin) regimen: at least 1 prior regimen must have contained a platinum-taxane combination
•Measurable disease as defined by RECIST 1.1
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Fresh or archived tumor tissue sample available for target expression analysis. \[Phase 1b only: Subjects' tumor tissue must test positive for target expression.\]
•Adequate hematologic and organ function as confirmed by laboratory values
•At least 3 weeks between last systemic chemotherapy and planned start of study treatment (4 weeks for prior investigational drugs, immunotherapy, radiotherapy, or biologics) for ovarian cancer
•At least 3 weeks between major surgery and planned start of study treatment; major incisions must have healed

Exclusion Criteria

•History of prior malignancy, with the exception of the following: malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician; or adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer; or adequately treated cervical carcinoma in situ without current evidence of disease.
•Uncontrolled infection requiring systemic antibiotics/antivirals/antifungals
•Evidence of complete or partial bowel obstruction
•Patients requiring IV hydration or parenteral nutrition
•Positive pregnancy test in females of child-bearing potential or pregnant or currently breastfeeding
•Known hypersensitivity to any component of study drug including potential subjects with a history of major immunologic reaction to any IgG-containing agent
•Inability to tolerate premedication with dexamethasone
•Uncontrolled cardiac disease, or myocardial infarction within the last 12 months, or left ventricular ejection fraction (LVEF) \< 50%, or QTcF interval \> 470 msec
•Class II, III or IV heart failure as defined by the NYHA functional class system
•Positive serology for hepatitis B or C, or known human immunodeficiency virus infection (HIV)

Arms & Interventions

SC-003

Phase 1a (Escalation) - IV infusion Phase 1b (Expansion) - IV infusion

Intervention: SC-003

SC-003 in combination with ABBV-181

Phase 1a (Escalation) - IV infusion of SC-003 followed by IV infusion of ABBV-181 Phase 1b (Expansion) - IV Infusion of SC-003 followed by IV infusion of ABBV-181

Intervention: SC-003 in combination with ABBV-181

Outcomes

Primary Outcomes

Adverse Events

Time Frame: 18 months (Phase 1a/1b)

Secondary Outcomes

Pharmacokinetics of SC-003: Ctrough (concentration at trough)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)
Pharmacokinetics of SC-003: CL (clearance)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)
Pharmacokinetics of SC-003: Tmax (time of maximum concentration)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)
Pharmacokinetics of SC-003: T1/2 (terminal half life)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)
Overall Response Rate(18 months (Phase 1a/1b))
Pharmacokinetics of SC-003: AUC (area under the curve)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min))
Pharmacokinetics of SC-003: Cmax (maximum concentration)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)
Pharmacokinetics of SC-003: Vss (volume of distribution at steady state)(Cycle 1 and 4: days 1 (pre-dose, post-dose: 30min, 6hr), 2, 4, 8, 15; Cycles 2, 3, and 5: day 1 (pre-dose, post-dose: 30min)