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

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02539719
• Other study ID #: SCRX003-001
• Status: Terminated
• Phase: Phase 1
• Start date: August 2015
• Est. completion date: January 2, 2019

Study information

• Verified date: January 2019
• Source: Stemcentrx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Terminated
• Enrollment: 74
• Est. completion date: January 2, 2019
• Est. primary completion date: January 2, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• SC-003

• SC-003 in combination with ABBV-181

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Stemcentrx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events		18 months (Phase 1a/1b)
Secondary	Overall Response Rate		18 months (Phase 1a/1b)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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