US-based biotechnology firm Seattle Genetics has started a Phase I / II clinical trial of SGN-CD33A (vadastuximab talirine), a new antibody-drug conjugate (ADC), to treat patients with relapsed or refractory acute myeloid leukemia (AML).
The trial is designed to evaluate SGN-CD33A monotherapy as a pre-conditioning regimen prior to an allogeneic stem cell transplant (alloSCT), and also as a maintenance therapy following a transplant.
Using the company’s new ADC technology, SGN-CD33A targets CD33, which is expressed on almost all AML cells regardless of subtype, cytogenetic abnormality, or underlying mutations.
Seattle Genetics Research and Development executive vice-president and chief medical officer Jonathan Drachman said: "Relapsed and refractory acute myeloid leukemia, or AML, remains among the most challenging unmet needs in cancer, and there continues to be little success in treating AML patients utilizing conventional salvage therapies.
"Our strategy with this trial is to evaluate the potential for SGN-CD33A to increase the percentage of patients who have no detectable leukemic cells prior to allogeneic transplant.
"Data suggest that patients who test negative for minimal residual disease prior to transplant are less likely to relapse. Separately, we will evaluate the potential for SGN-CD33A to maintain remissions after allogeneic transplant."
Around 100 patients at multiple US test centres will be enrolled in the open-label, multi-centre Phase I/II trial, which is a two-part (A and B) study.
The trial’s part A will examine SGN-CD33 as cytoreduction pre-conditioning and part B will evaluate SGN-CD33A in post-alloSCT as a maintenance regimen.
Each part will include a Phase I safety evaluation followed by a Phase II expansion for activity, while patient enrolment will be carried out in both parts concurrently.
The primary endpoints in Phase I are determination of the maximum tolerated dose (MTD), and the safety and tolerability profiles of SGN-CD33A in both pre and post-alloSCT settings.
The Phase II primary endpoints are to evaluate the one-year survival rates of patients treated with SGN-CD33A at the recommended dose.
It will also assess the rate of minimal residual disease negativity, as well as the safety and tolerability of SGN-CD33A.
Image: Bone marrow aspirate showing acute myeloid leukaemia. Photo: courtesy of VashiDonsk.