Ovarian Cancer
Conditions
Keywords
Platinum-Resistant, Refractory
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.
Interventions
DRUGSC-003
DRUGSC-003 in combination with ABBV-181
Sponsors
Stemcentrx
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse Events | 18 months (Phase 1a/1b) |
Secondary
| Measure | Time frame |
|---|---|
| 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: 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 |
| Overall Response Rate | 18 months (Phase 1a/1b) |
| 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 |
| 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: 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 |
| 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 |
Countries
United States
Outcome results
None listed