Date: 2014-12-06
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Seattle Genetics (USA - WA)
Product: SGN-CD19A
Action
mechanism: antibody drug conjugate. SGN-CD19A is an antibody drug conjugate (ADC) comprised of an anti-CD19 monoclonal antibody linked to a synthetic cytotoxic cell-killing agent, monomethyl auristatin F (MMAF), using Seattle Genetics’ industry-leading proprietary technology. The ADC is designed to be stable in the bloodstream, and to release its cytotoxic agent upon internalization into CD19-expressing tumor cells. CD19 is expressed in B-cell ALL and NHL, including DLBCL. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity. Preclinical data presented at the 2011 American Association for Cancer Research Annual Meeting demonstrated that SGN-CD19A effectively binds to target cells, internalizes and induces potent cell-killing activity and durable tumor regressions at low doses in multiple preclinical cancer models. SGN-CD19A is being evaluated in two ongoing phase 1 clinical trials for patients with B-cell ALL and aggressive NHL.
Disease: acute lymphoblastic leukemia
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This is a phase 1, open-label, dose-escalation, multicenter study to evaluate the safety and tolerability of SGN-CD19A in adult and pediatric patients with relapsed or refractory B-lineage acute lymphoblastic leukemia (B-ALL), Burkitt lymphoma or leukemia, or B-lineage lymphoblastic lymphoma (B-LBL).(NCT01786096)
Latest
news: * On December 6, 2014, Seattle Genetics presented data from two ongoing phase 1 clinical trials evaluating SGN-CD19A, an antibody-drug conjugate (ADC) in development for the treatment of B-cell malignancies, including non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL), at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA December 6-9, 2014. Interim Analysis of a Phase 1 Study of the Antibody-Drug Conjugate SGN-CD19A in Relapsed or Refractory B-Lineage Acute Leukemia and Highly Aggressive Lymphoma (Abstract #963): In this phase 1 trial, adult and pediatric patients with relapsed or refractory B-lineage ALL and highly aggressive lymphoma, including B-cell lymphoblastic lymphoma (LBL) and Burkitt lymphoma were enrolled. Data were reported from 51 adult patients. The median age of adult patients was 43 years and the median number of prior systemic therapies was two, with 14 patients (27 percent) having received a prior allogeneic stem cell transplant. The primary endpoints of the ongoing clinical trial are to estimate the maximum tolerated dose and to evaluate the safety of SGN-CD19A. In addition, the trial is evaluating antitumor activity, pharmacokinetics, progression-free survival and overall survival. In this dose-escalation study, patients received SGN-CD19A at either 0.3 to 2.3 mg/kg weekly or 4 to 6 mg/kg every three weeks. Key findings presented by Amir Fathi, M.D., Massachusetts General Hospital, include: At the time of data analysis, dose escalation is ongoing. Safety analysis included data from 51 patients, including 18 patients treated every three weeks and 33 patients treated weekly. Of the 14 ALL and LBL adult patients evaluable for response treated every three weeks, five patients (36 percent) achieved an objective response, including four patients (29 percent) with a complete remission and one patient (seven percent) with a partial remission. Eight patients (57 percent) achieved stable disease and one patient (seven percent) had disease progression.
Of the 29 ALL and LBL adult patients evaluable for response treated with weekly dosing, six patients (20 percent) achieved an objective response, including five patients (17 percent) with a complete remission and one patient (three percent) with a partial remission. Ten patients (34 percent) achieved disease stabilization and 13 patients (45 percent) had disease progression.
The most common adverse events of any grade occurring in 25 percent or more of adult patients treated every three weeks (18 patients) and weekly (33 patients), respectively, were fever (56 and 55 percent), chills (33 and 56 percent), fatigue (33 and 55 percent), headache and nausea (28 and 55 percent), blurred vision (39 and 36 percent), vomiting (28 and 42 percent) and febrile neutropenia (28 and 33 percent).
Symptoms related to keratopathy were reported in 27 patients. All symptoms were Grade 1/2; no Grade 3 symptoms were reported. The most common symptoms were blurred vision, dry eye and photophobia. Grade 3 or 4 keratopathy was reported in 10 patients and the majority had experienced improvement and/or resolution at last follow-up. Ocular symptoms and corneal findings were managed with steroid eye drop treatment and dose modifications. Prophylactic eye drops were instituted early in the trial and appear to reduce the severity of corneal events in the weekly treatment schedule.
The SGN-CD19A phase 1 clinical trials are ongoing and additional data from both studies, including the impact of alternative dosing strategies, are planned in 2015. The company plans to initiate a randomized phase 2 trial evaluating SGN-CD19A in combination with R-ICE chemotherapy for second-line DLBCL during 2015.
