Date: 2015-10-29
Type of information: Initiation of the trial
phase: 2
Announcement: initiation of the trial
Company: Seattle Genetics (USA - WA)
Product: denintuzumab mafodotin (SGN-CD19A) in combination with the second-line salvage regimen of rituximab (Rituxan®), ifosfamide, carboplatin and etoposide (RICE)
Action
mechanism: antibody drug conjugate. SGN-CD19A is an antibody drug conjugate (ADC) comprised of an anti-CD19 monoclonal antibody, denintuzumab, 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.
Disease: relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or Grade 3b follicular lymphoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The purpose of this randomized, open-label study is to evaluate the safety and efficacy of denintuzumab mafodotin plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) when compared to RICE alone in the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or Grade 3b follicular lymphoma. Eligible patients must also be candidates for autologous stem cell transplant. Patients will be randomly assigned in a 1:1 ratio to receive 3 cycles of study treatment with either denintuzumab mafodotin + RICE or RICE alone. The study will assess whether there is a difference between the 2 groups in the side effects that are reported and the number of patients who achieve complete remission at the end of their study treatment.(NCT02592876)
Latest
news: * On October 29, 2015, Seattle Genetics announced the initiation of a randomized phase 2 clinical trial of denintuzumab mafodotin (SGN-CD19A) in combination with the second-line salvage regimen of rituximab (Rituxan®), ifosfamide, carboplatin and etoposide (RICE), for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of aggressive non-Hodgkin lymphoma. The study is intended to evaluate the activity and safety of the combination regimen compared to RICE alone. Denintuzumab mafodotin is an antibody-drug conjugate (ADC) targeting CD19, a protein expressed uniformly on almost all B-cell malignancies. The ADC is designed to be stable in the bloodstream and release its cytotoxic agent upon internalization into CD19-expressing cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects associated with traditional chemotherapy while enhancing antitumor activity. In this phase 2 randomized, open-label, multi-center clinical trial, approximately 150 relapsed/refractory DLBCL or grade 3B follicular lymphoma patients who are eligible for an autologous stem cell transplant (ASCT) will be randomized to receive RICE either with or without denintuzumab mafodotin every three weeks for three cycles. The primary endpoint is to compare the complete remission rates between the two study arms. Secondary endpoints include safety of the combination regimen, progression-free survival, overall survival and the number of patients who are able to undergo autologous transplant. At the 2014 American Society of Hematology (ASH) Annual Meeting, data were presented from an ongoing phase 1 trial of relapsed/refractory aggressive non-Hodgkin lymphoma patients who received single-agent denintuzumab mafodotin every three weeks. Of the 51 evaluable patients, including 45 DLBCL patients, the objective response rate across all dose levels was 35 percent, including 20 percent complete remissions and 16 percent partial remissions. In the subset of patients who had relapsed disease, the objective response rate was 55 percent, including 32 percent complete remissions and 23 percent partial remissions. 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). Ocular symptoms and corneal findings were superficial, generally reversible, and were managed with steroid eye drop treatment and dose modifications. The majority of affected patients experienced improvement and/or resolution at last follow up. Furthermore, no significant myelosuppression or peripheral neuropathy were observed, suggesting that denintuzumab mafodotin may be well tolerated in combination with multi-agent chemotherapy.
