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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: SC-003
* Drug: SC-003 in combination with ABBV-181


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC-003<br>Phase 1a (Escalation) - IV infusion Phase 1b (Expansion) - IV infusion | Drug: SC-003<br> <br> |
| Experimental: SC-003 in combination with ABBV-181<br>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 | Drug: SC-003 in combination with ABBV-181<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | 18 months (Phase 1a/1b) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: 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: 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: 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platinum-Resistant, Refractory