Study of SC-003 Alone and in Combination With ABBV-181 in Subjects With Platinum-Resistant/Refractory Ovarian Cancer

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

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).

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.

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