Study of SC-003 Alone and in Combination With ABBV-181 in Subjects With Platinum-Resistant/Refractory Ovarian Cancer
Phase 1
Terminated
- Conditions
- Ovarian Cancer
- Interventions
- Drug: SC-003 in combination with ABBV-181
- Registration Number
- NCT02539719
- Lead Sponsor
- Stemcentrx
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 74
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)
- Previous treatment with a pyrrolobenzodiazepine (PBD)-based drug
Additional exclusion criteria for the SC-003 and ABBV-181 combination treatment regimen:
- History of inflammatory bowel disease
- Active autoimmune disease, with exceptions of psoriasis not requiring systemic treatment, vitiligo, type 1 diabetes mellitus and hypothyroidism
- History of primary immunodeficiency, allogeneic bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis
- History of immune-mediated pneumonitis
- Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SC-003 SC-003 Phase 1a (Escalation) - IV infusion Phase 1b (Expansion) - IV infusion SC-003 in combination with ABBV-181 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
- Primary Outcome Measures
Name Time Method Adverse Events 18 months (Phase 1a/1b)
- Secondary Outcome Measures
Name Time Method 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