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: non-Hodgkin lymphoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
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 Non-Hodgkin Lymphoma (Abstract #1741). Data were reported from 52 patients with relapsed or refractory NHL, including 45 patients with diffuse large B-cell lymphoma (DLBCL), three patients with grade 3 follicular lymphoma and four patients with mantle cell lymphoma. Of the 52 patients, 30 patients (58 percent) were refractory to their last therapy and 22 patients (42 percent) were relapsed. Fourteen patients (27 percent) had received a prior autologous stem cell transplant. The median age of patients was 65 years. 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 receive SGN-CD19A on an every three week schedule. Patients with stable disease or better are eligible to continue treatment with SGN-CD19A. Key findings in a poster presentation by Craig Moskowitz, M.D. Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, include: The maximum tolerated dose was not exceeded after escalating to 6 milligrams per kilogram (mg/kg) every three weeks. In addition, evaluation of an every six week dosing schedule is underway and enrollment is ongoing. * On June 1, 2014, Seattle Genetics announced the presentation of interim phase 1 clinical data from SGN-CD19A, an antibody-drug conjugate (ADC) in development for the treatment of B-cell malignancies, at the American Society of Clinical Oncology (ASCO) 50th Annual Meeting being held May 30 to June 3, 2014 in Chicago,. Interim analysis of a phase 1, open-label, dose-escalation study of SGN-CD19A in patients with relapsed or refractory B-lineage non-Hodgkin lymphoma (Abstract #8505). Data were reported from 37 patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), including 32 patients with diffuse large B-cell lymphoma (DLBCL), four patients with mantle cell lymphoma (MCL) and one patient with Grade 3 follicular lymphoma. The median age of patients was 65 years and the median number of prior systemic therapies was two, with 10 patients (27 percent) having received a prior autologous stem cell transplant. Among enrolled patients, eight percent were primary refractory, 54 percent were refractory to their last treatment and 38 percent had relapsed following a response to their last treatment. 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 receive a single dose of SGN-CD19A on an every 3-week basis. Key findings included: • No dose limiting toxicity was observed in the first cycle for any patients. Adverse events were observed in the 6 milligrams per kilogram (mg/kg) dosing regimen after the first cycle, therefore enrollment was discontinued. The 3, 4 and 5 mg/kg cohorts are being expanded, and the trial continues to enroll. • At the time of data analysis, of the 37 patients treated across all dose levels, the objective response rate observed was 30 percent (11 patients). Six patients (16 percent) achieved a complete remission, five (14 percent) achieved a partial remission, 13 (35 percent) had stable disease and 13 (35 percent) had progressive disease as best response. The clinical trial is ongoing with nine of the 37 patients (24 percent) remaining on treatment and new patients continuing to be enrolled. • The most common adverse events of any grade occurring in more than 30 percent of patients were blurred vision (51 percent), fatigue (38 percent), dry eye (35 percent), constipation (30 percent) and keratopathy (30 percent). Grade 3 or higher adverse events observed in two or more patients included blurred vision (six patients), keratopathy (three patients), low platelet count (three patients) and anemia (three patients).
Of the 51 patients evaluable for response, 18 patients (35 percent) achieved an objective response, including 10 patients (20 percent) with a complete remission and eight patients (16 percent) with a partial remission. Thirteen patients (25 percent) achieved stable disease and 20 patients (39 percent) had disease progression.
Antitumor activity appeared to be higher in relapsed patients. Of the 22 relapsed patients, 12 patients (55 percent) achieved an objective response, including seven patients (32 percent) with a complete remission and five patients (23 percent) with a partial remission. Six patients (27 percent) achieved stable disease and four patients (18 percent) had disease progression.
The most common adverse events of any grade occurring in more than 25 percent of patients were blurred vision (60 percent), dry eye (46 percent), fatigue (38 percent), constipation (33 percent) and keratopathy (31 percent). Most ocular symptoms were Grade 1/2. The majority of patients with Grade 3 or 4 ocular symptoms and/or corneal findings experienced improvement and/or resolution at last follow-up. Ocular symptoms and corneal findings were managed with steroid eye drop treatment and dose modifications.
