The Targeted Pulse: Discover Key FDA Actions in Leukemia and NSCLC and The Significant Effects of TKIs in CML and CLL

Revumenib Crosses the Finish Line For KMT2A-Rearranged Acute Leukemia

Revumenib (SNDX-5613) has received FDA approval for the treatment of adult and pediatric patients with relapsed/refractory (R/R) KMT2A-rearranged acute leukemia. This approval is based on data from the phase 1/2 AUGMENT-101 trial (NCT04065399), which evaluated the efficacy and safety of the drug in a total of 94 patients with R/R KMT2Ar acute leukemia, acute lymphoblastic leukemia (ALL)/mixed phenotype acute leukemia, and acute myeloid leukemia (AML). Minimal residual disease was also evaluated in 10 patients as part of the study.

“KMT2A-rearrangements occur in patients with acute myeloid and ALL, in adults, children, and overall, and have a poor prognosis. Revumenib gives hope to those with relapsed and refractory KMT2Ar disease. I hope to see this agent investigated in clinical trials for newly diagnosed KMT2Ar AML and ALL,” Eytan M. Stein, MD, chief of the leukemia service and director of the Program for Drug Development in Leukemia, Division of Hematologic Malignancies, at Memorial Sloan Kettering Cancer Center in New York, New York, told Targeted Oncology^TM.

Dato-DXd Moves Into Last Phase For FDA Approval in EGFR-Mutated NSCLC

A newly submitted biologics license application seeks accelerated approval of datopotamab deruxtecan (Dato-DXd) for the treatment of metastatic or locally advanced EGFR-mutated non–small cell lung cancer (NSCLC). This indication replaced the initial nonsquamous NSCLC application following feedback from the FDA. The submission is based on data from the following trials/phases evaluating Dato-DXd in various designs: the phase 2 and phase 3 TROPION-Lung01 (NCT04656652), TROPION-Lung05 (NCT04484142), and TROPION-PanTumor01 (NCT03401385).

“TROPION-Lung01 was designed to test the potential to improve upon standard-of-care chemotherapy in patients with a broad, previously treated, advanced lung cancer patient population. The results, together with data from TROPION-Lung05, showed an especially pronounced benefit for patients with an EGFR mutation, which informed our discussions with the FDA and the decision to seek accelerated approval of datopotamab deruxtecan in this patient population. TROPION-Lung01 has also provided exciting exploratory data supporting our biomarker development, which will be validated in ongoing and planned phase 3 lung cancer trials,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, stated in the press release.

“Managing CML Is a Marathon”: Gain Insights on Clinical and Real-World Data

Maintaining open and personalized communication with patients treated for chronic myeloid leukemia (CML) is a necessity due to the growing arsenal of (TKIs) and the time spent on treatment. Certain patients achieve an early response, but for others, treatment can be lifelong, requiring prompt management of serious adverse events, Michael Mauro, MD, explained. Mauro explores the current challenges and real-world data on CML, highlighting new TKIs that have a significant effect.

“Managing CML is a marathon requiring a minimum of 3 to 5 years of therapy even with our current best thoughts on the curative pathway, and that is only for a select group of patients. This group of patients is able to achieve an early and optimum response. [However], for the majority of patients, it is chronic or even lifelong therapy—more like an ultramarathon. Managing adherence, compliance, [and] tolerability and keeping the lines of communication open with patients is essential, as adverse events are often lower grade, though serious ones must be managed quickly,” Mauro, director of the CML program in the leukemia service at Memorial Sloan Kettering Cancer Center in New York, New York, stated in an interview with Targeted Oncology^TM.

Key Updates in TKI Therapy Reveal A Notable Challenge in CLL

A challenge in managing chronic lymphocytic leukemia (CLL) is disease progression for patients who have been treated with covalent Bruton's tyrosine kinase (BTK) inhibitors and venetoclax (Venclexta), according to Nicole Lamanna, MD. At the 42nd Annual Chemotherapy Symposium Foundation, hosted by Physicians' Education Resource, LLC, Lamanna reviewed a range of treatment options for heavily pre-treated CLL, discussing pertinent trials as well as research on the potential role of chimeric antigen receptor (CAR) T-cell therapy in CLL.

“Our patients who have relapsed multiple times are becoming a new clinically unmet need. With the covalent and the venetoclax- based therapies, patients can be bridged to a non-covalent, like ibrutinib [Imbruvica]. These patients are not going to last that long, so they need to get on a clinical trial or bridge or receive CAR T-cell therapy if they’re eligible,” Lamanna said. Lamanna is an associate clinical professor of medicine in the Hematologic Malignancies Section of the Hematology/Oncology Division at Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York.

Discussing Quadruplet Therapy in Transplant-Eligible Multiple Myeloma

Marc J. Braunstein, MD, PhD, FACP, and hematology/oncology fellow and Olivia Main, MD, discussed a case involving a patient with transplant-eligible multiple myeloma. In the discussion, they highlight data from the phase 2 GRIFFIN (NCT02874742) and PERSEUS (NCT03710603) trials, explaining the efficacy of a quadruplet regimen vs a triplet regimen for this patient population.

“Those who received the quadruplet regimen had statistically significant improvement…This was also seen both at the end of the induction therapy as well as at the end of final analysis. [The percentage of] those who achieved a CR or better after the end of induction was around 19% in the D-RVd group, but we saw this even further depth of response increase at the end of the final analysis to 83% in those who received the quadruplet regimen, compared with 60% of patients who received the triplet regimen alone. This led to another study, the PERSEUS trial, which also demonstrated that the quadruplet regimen improved the depth of responses for these patients,” Main explained in the discussion with Peers & Perspectives in Oncology.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

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