Amer Zeidan, MBBS, MHS, Yale Cancer Center, New Haven, Connecticut, shares the results of a phase 2 trial which evaluated the safety and efficacy of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) among patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for inductive chemotherapy.

Dr Zaidan stated, “this double oral therapy combination looks quite exciting, and it could allow patients to receive very good doublet therapy for AML without needing to come frequently for [azacitidine] (AZA) injections, and also potentially in the future could be backbone to add drugs on for triplets such as IDH inhibitors, FLT3 inhibitors.”

Transcript:

My name is Amer Zeidan, I'm a professor of medicine at Yale University and the chief of the Division of Hematologic Malignancies at Yale Cancer Center.

I'm joining you today to talk about a study that we have presented at the ASCO meeting last June in Chicago, where we discussed our phase 2 trial in which we combined oral decitabine-cedazuridine with venetoclax as a frontline treatment for older and unfit patients with newly diagnosed acute myeloid leukemia. 

Many of you know that azacitidine and venetoclax (AZA-VEN) has been now a standard of care for several years in patients who are older and unfit for intensive chemotherapy. But azacitidine requires repeated visits to the clinic for infusion and imposes significant time burden on patients, and therefore there has been an interest in using an oral substitute for that. Also, we know that decitabine and azacitidine have similar clinical effectiveness based on multiple registries and clinical analyses. There's an oral version of decitabine in which decitabine is combined with a drug called cedazuridine that inhibits degradation of decitabine, and therefore allows oral use.

This drug called DEC-C or decitabine-cedazuridine is already approved in the US for high-risk MDS as a monotherapy, but what we did in this study is we combined this drug, which is given for 5 days at the standard dose of 30mg of decitabine with 100mg of cedazuridine. We combined that with venetoclax, and we studied that in a phase 2b study that included 101 patients. The primary end point of that study was a complete response (CR) rate. We of course, did an extensive safety assessment.

What we found in this study is that the CR rate of the combination was 47%. The complete response seems in [line] or actually a little bit higher than the VIALE-A trial that led to approval of azacitidine and venetoclax in patients with AML. We also saw that the response was durable. The overall survival was 15 and a half months. Again, in line with what we saw with VIALE-A.

The safety looked pretty good. As expected in this patient population, there was myelosuppression, febrile neutropenia, but the early mortality was less than 7 to 9%, similar to VIALE-A. The rate of complications was again, along the lines of what we typically see with AZA-VEN, and generally was manageable with antibiotic prophylaxis and transfusion support. Also, we saw that there were no significant drug interactions between the decitabine-cedazuridine and venetoclax. Of course, there was a need to reduce venetoclax through multiple cycles to mitigate the myelosuppression, and that allowed several patients to be able to continue on this prolonged therapy.

In summary, I think this double oral therapy combination looks quite exciting, and it could allow patients to receive very good doublet therapy for AML without needing to come frequently for AZA injections, and also potentially in the future could be backbone to add drugs on for triplets such as IDH inhibitors, FLT3 inhibitors. Hopefully this will become available in the US pending a regulatory review of this combination and the results of this study, which is called ASCERTAIN-V study. Thank you so much for listening.

Source:

Zeidan A, Griffiths E, Dinardo C, et al. An all-oral regimen of decitabine-cedazuridine (DEC-C) plus venetoclax (VEN) in patients (pts) with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive induction chemotherapy: Results from a phase 2 cohort of 101 pts. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 6504.