Seattle Genetics, Inc. (Nasdaq:SGEN) today highlighted clinical data from two antibody-drug conjugate (ADC) programs in development by Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY) that utilize Seattle Genetics’ technology. The data were presented at the 54 th American Society of Hematology (ASH) Annual Meeting and Exposition being held December 8-11, 2012 in Atlanta, GA. Phase I data from both ADCs, an anti-CD22 ADC (DCDT2980S, RG7593) and an anti-CD79b ADC (DCDS4501A, RG7596), demonstrated antitumor activity in relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) patients at generally well-tolerated doses. These ADC programs are currently being evaluated in a phase II clinical trial for patients with relapsed or refractory B-cell NHL. “Genentech’s phase I data and their advancement of these two ADCs into phase II clinical development, as well as their utilization of our technology in six other clinical-stage programs, illustrates their commitment to ADCs as an innovative, targeted approach to treat cancer,” said Eric Dobmeier, Chief Operating Officer of Seattle Genetics. “Across our ADC collaborations, there is broad potential for our industry-leading technology to address the significant need for more effective and better tolerated treatment options.” Anti-CD22-MMAE and anti-CD79b-MMAE are ADCs designed to deliver potent cytotoxic treatment to targeted cells with improved tolerability. With over a decade of experience and knowledge in ADC innovation, Seattle Genetics has developed proprietary technology employing synthetic cytotoxic agents, such as monomethyl auristatin E (MMAE), and stable linker systems that attach these cytotoxic agents to the antibody. Seattle Genetics’ linker systems are designed to be stable in the bloodstream and release the potent cell-killing agent once inside targeted cancer cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. ADCETRIS ® (brentuximab vedotin) is the first drug approved utilizing Seattle Genetics’ ADC technology. A Phase I Study of the Anti-CD79b Antibody-Drug Conjugate (ADC) DCDS4501A Targeting CD79b in Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma (Abstract #56) A phase I clinical trial is being conducted to evaluate the safety and activity of DCDS4501A in patients with relapsed or refractory B-cell NHL. DCDS4501A is an ADC consisting of an anti-CD79b monoclonal antibody conjugated to the cytotoxic agent MMAE using Seattle Genetics’ ADC technology. In this analysis, 47 patients were evaluable for safety and 32 were evaluable for efficacy.
Key findings included:
- Patients enrolled in the study were diagnosed with a variety of types of B-cell NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, mantle cell lymphoma and marginal zone lymphoma. All patients had relapsed or refractory disease and were heavily pretreated, with a median of four prior systemic therapies. Ninety-six percent of patients had received prior rituximab and 29 percent had received a prior autologous stem cell transplant (ASCT). The median age of patients enrolled was 64.
- Patients received doses ranging from 0.1 milligrams per kilogram (mg/kg) to 2.4 mg/kg on an every three week basis, and 2.4 mg/kg was selected as the recommended phase II dose.
- Among all 32 patients evaluable for efficacy, ten patients (31 percent) had an objective response to single-agent DCDS4501A. Among the 17 patients treated at doses greater than or equal to 1.8 mg/kg, eight patients (47 percent) had an objective response.
- The most common adverse events were neutropenia, diarrhea, fever, nausea, fatigue, anemia, hyperglycemia and thrombocytopenia. Most adverse events were Grade 1 or 2.
- The most common Grade 3 or 4 adverse events were neutropenia, thrombocytopenia, anemia and leukopenia.
- Patients enrolled in the study were diagnosed with a variety of types of B-cell NHL, including DLBCL, follicular lymphoma, transformed follicular lymphoma and small lymphocytic lymphoma. All patients had relapsed or refractory disease and were heavily pretreated, with a median of four prior systemic therapies. All patients had received prior rituximab and 16 percent had received a prior autologous stem cell transplant. The median age of patients enrolled was 66.
- Patients received doses ranging from 0.1 mg/kg up to 3.2 mg/kg on an every three week basis, and 2.4 mg/kg was selected as the recommended phase II dose.
- Among all 33 patients evaluable for efficacy, nine patients (27 percent) had an objective response to single-agent DCDT2980S. Among the 17 patients treated at doses greater than or equal to 1.8 mg/kg, seven patients (41 percent) had an objective response, including one complete response and six partial responses.
- The most common adverse events were fatigue, diarrhea, nausea, neutropenia and decreased appetite. Most adverse events were Grade 1 or 2.
- The most common Grade 3 or 4 adverse events were neutropenia, anemia, diarrhea and peripheral neuropathy.