US-based Senesco has commenced the third cohort in its Phase Ib/IIa study for its lead therapeutic candidate SNS01-T, a therapy designed to selectively trigger apoptosis in B-cell cancers such as multiple myeloma, and diffuse large B-cell and mantle cell lymphomas.
Upon reviewing the study's second cohort results, the Data Review Committee (DRC) for the candidate concluded that it was safe, and approved the commencement of new the cohort.
After establishing that the drug was well-tolerated at a dose of 0.05mg/kg, the DRC gave its nod for the escalation of the dose level to 0.2 mg/kg.
Neither of the first two cohorts has reported any drug-related serious adverse events or dose limiting toxicities, said the company.
Senesco's DRC independent member and Cedars-Sinai Comprehensive Cancer Center Research and Myeloma Programs director Dr Brian Durie said the study has seen disease stabilisation and no drug-related safety issues at the lower dose levels.
"However, now that patients will be receiving higher doses, Senesco has the opportunity to ascertain whether SNS01-T can show significant efficacy in patients as well," Durie said.
As part of the open-label, multiple-dose, dose-escalation study, the company will administer SNS01-T by intravenous infusion to nearly 15 patients with relapsed or refractory multiple myeloma, mantle cell (MCL) or diffuse large B-cell lymphoma (DLBCL) to observe the safety and tolerability.
Furthermore, the study will also observe the influence of SNS01-T on tumor response and assess the time to relapse or progression using multiple well-established metrics, including measurement of monoclonal protein in multiple myeloma and CT imaging in MCL and DLBCL.
For the first cohort, Senesco dosed patients with 0.0125mg/kg per dose twice a week for about 6 weeks, and then 0.05mg/kg during the second cohort.
While 0.2mg/kg is proposed for third cohort, the company plans a further increase in the fourth cohort, to 0.375mg/kg.
The higher doses of 0.375 mg/kg and 0.2 mg/kg have already yielded good results, such as survival and inhibition of tumour growth, when the candidate was applied in mouse models of multiple myeloma, diffuse large B-cell lymphoma and mantle cell lymphoma as part of the study.
Senesco chairman Dr Harlan Waksal said; "In cohort 3 patients will now be receiving dose levels of SNS01-T that are in the same range where we started to observe efficacy in preclinical cancer models."
Image: Micrograph of a plasmacytoma, the histologic correlate of multiple myeloma. Photo: Courtesy of Nephron.