ASH 2023 | Inotuzumab ozogamicin & venetoclax in the treatment of B-ALL: findings from a Phase I trial

So this is an investigator sponsored trial that has been conducted by myself and my colleagues at the Dana Farber Cancer Institute, and really inspired by the unmet need for patients with relapse B-ALL. And for these patients, inotuzumab ozogamicin, which is an anti-CD22 antibody-drug conjugate, induces high response rates, but the response rates are not 100% and those responses in the INO-VATE trial that led to the approval of this drug were typically not durable, lasting just a couple of months. 

And so we were interested in seeing if we could enhance those responses with a doublet therapy, particularly introducing venetoclax, a BCL2 inhibitor, that preclinical studies really demonstrate that this drug has activity in B-ALL, and the side effects of this drug and inotuzumab are different, non-overlapping. And so we said, can we put these two drugs together and create synergy and deeper and more durable responses. 

So this is a Phase I trial really designed to demonstrate the safety of combining these drugs. And at this year’s ASH we present the dose-escalation phase. Dose level one was 200mg daily, which was well tolerated. And then we escalated to 400mg daily of venetoclax, administered with a three day ramp up and then 21 days, in combination with the standard approved dose of inotuzumab. And we really saw that this was was safe. We didn’t see any DLTs or unexpected toxicities. In particular, there were not any episodes of venoocclusive disease or sinusoidal obstructive syndrome, or SOS. We did not see issues with cytopenias or prolonged recovery. So this is a safe combination and we’re currently continuing to enroll in a dose-expansion, with an attempt to get more efficacy data. And the patients treated thus far, all the patients have achieved a complete remission, MRD-negative in the vast majority of them. So we’re really encouraged by this combination and look forward to continuing to develop the regimen.