A Promising New Type of Drug for Aggressive Leukemia

Michael Rosensweig with dog

Michael Rosensweig with Snow, photographed in the summer of 2020, before his latest disease recurrence.

When Michael Rosensweig learned in May 2021 that his acute myeloid leukemia (AML) had returned for a fourth time, it was difficult news to receive. He had been in remission for more than eight years.

This time, though, the treatment playbook was different. Rather than facing another course of intensive chemotherapy requiring weeks of hospitalization, Michael found out that he qualified for a groundbreaking clinical trial of an experimental targeted therapy called SNDX-5613. The drug, which is in a new class called menin inhibitors, was developed based on research conducted in Memorial Sloan Kettering Cancer Center labs.

On December 13, 2021, at the American Society of Hematology (ASH) annual meeting, MSK hematologic oncologist Eytan Stein presented initial results for the first clinical trial of SNDX-5613. The findings revealed that more than half of patients with certain molecular changes in their tumor responded to the drug. These changes are either an MLL rearrangement or an NPM1 mutation.

“People with these types of alterations tend to have very aggressive disease,” says Dr. Stein, who leads MSK’s Program for Drug Development in Leukemia. “What we’ve seen in this study is very promising, especially for this patient population.” Combined, MLL rearrangements and NPM1 mutations occur in about 40% of people with AML. In addition, MLL rearrangements also occur in acute lymphocytic leukemia.

Blocking a Cancer-Causing Protein

The phase 1 trial enrolled 59 patients at eight hospitals around the country. All of them had seen their AML come back after other treatments, like Michael, or had never responded well to traditional chemotherapy drugs in the first place.

Additionally, all of them had cancer that was caused by either a mutation in a gene called NPM1 or an MLL rearrangement, a kind of chromosome abnormality in which one piece of a chromosome breaks off and attaches to another chromosome. Both of these changes require a protein called menin to drive cancer growth. By blocking the interaction of menin with mutated NPM1 or the MLL rearrangement, SNDX-5613 turns leukemia cells back into normal blood cells.

What we've seen in this study is very promising, especially for this patient population.
Eytan M. Stein hematologic oncologist

The early research on menin inhibitors was done by physician-scientist Scott Armstrong — who now works at Dana-Farber Cancer Institute in Boston — when he was at MSK in the mid-2010s. Ross Levine, Chief of the Molecular Cancer Medicine Service in MSK’s Human Oncology & Pathogenesis Program, also participated in that work.

At the ASH meeting, Dr. Stein reported that 55% of patients responded to the drug, and 24% had a complete response or a complete response with partial hematologic recovery, which means that no cancer was detectable in their blood. Of the 24% of patients who achieved a remission, more than 90% of them were negative for measurable residual disease, meaning that by the most sensitive methods, leukemia could not be detected.

Back to top

A Better Quality of Life During Treatment

SNDX-5613 is a pill that’s taken at home. “Being able to do treatment from home and just be normal for a while was nice, as opposed to being stuck in a hospital bed for months,” Michael says. “The drug did what it was supposed to do and was much easier on my body.”

Michael says he experienced no side effects, which was a relief compared with his earlier chemotherapy treatments. Overall, the side effects observed in the trial were not serious, and no patients had to drop out because of them.

“Menin inhibitors appear to be very well tolerated and are easy to take,” Dr. Stein says. “This is everything you want in a targeted therapy.”

Back to top

Expanding Options for a Challenging Disease

Some of the patients in the trial have done well for up to six months, but the researchers are not sure how long the drug will continue to work. For that reason, nine patients from the trial, including Michael, have gone on to receive a stem cell or bone marrow transplant (BMT). Because transplants require that patients have very low levels of cancer in their blood, it’s likely that many of these transplants would not have been possible without SNDX-5613.

Menin inhibitors appear to be very well tolerated and are easy to take. This is everything you want in a targeted therapy.
Eytan M. Stein hematologic oncologist

Michael received the BMT — his fourth one — in October. It was performed by Sergio Giralt, Deputy Division Head of MSK’s Division of Hematologic Malignancies. The stem cells he received were from an unrelated donor who was found in a public registry. The 32-year-old software engineer was first diagnosed with AML when he was a junior at the Massachusetts Institute of Technology. He’s now doing well and is home from the hospital continuing his recovery.

Based on the results from this phase 1 trial, a phase 2 trial has already been launched. That trial will include pediatric as well as adult patients. Dr. Stein and his collaborators are also collecting samples from all trial participants to learn as much as they can about how the drug works.


Key Takeaways
  • MSK leukemia expert Eytan Stein is leading the first-ever trial of a leukemia drug called SNDX-5613.
  • The drug, a targeted therapy, is in a new class called menin inhibitors.
  • At the American Society of Hematology annual meeting, Dr. Stein presented results from the trial, which found that about half of patients with certain genetic alterations respond to the drug.
  • One of those patients, Michael Rosensweig, was able to have a bone marrow transplant thanks to SNDX-5613.
Back to top

The SNDX-5613 trial was funded by Syndax Pharmaceuticals.

Dr. Stein’s disclosures are as follows: Foghorn Therapeutics: Consultancy; Blueprint Medicines: Consultancy; Gilead Sciences, Inc.: Consultancy; Abbvie: Consultancy; Janssen Pharmaceuticals: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; PinotBio: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Novartis: Consultancy; Agios Pharmaceuticals, Inc: Consultancy; Syros Pharmaceuticals, Inc.: Consultancy; Syndax Pharmaceuticals: Consultancy.