Bosutinib Approved for Pediatric Patients With Chronic Myelogenous Leukemia
The FDA approved bosutinib for pediatric patients 1 year of age and older with chronic phase (CP) Ph+ chronic myelogenous leukemia (CML) that is newly diagnosed or resistant/intolerant to prior therapy. The FDA also approved a new capsule dosage form available in strengths of 50 mg and 100 mg.
Efficacy was evaluated in the BCHILD trial (NCT04258943), a multicenter, nonrandomized, open-label trial conducted to identify a recommended bosutinib dose in pediatric patients with newly diagnosed CP Ph+ CML and resistant/intolerant CP Ph+ CML, to estimate the safety, tolerability, and efficacy, and to evaluate bosutinib pharmacokinetics in this patient population. The trial enrolled 28 patients with resistant/intolerant CP Ph+ CML treated with bosutinib at 300 mg/m2 to 400 mg/m2 orally once daily and 21 patients with newly diagnosed CP Ph+ CML treated at 300 mg/m2 once daily.
The major efficacy outcome measures included major cytogenetic response, complete cytogenetic response, and major molecular response (MMR). For pediatric patients with newly diagnosed CP Ph+ CML, the major and complete cytogenetic responses were 76.2 percent (95% CI: 52.8, 91.8) and 71.4 percent (95% CI: 47.8, 88.7), respectively. The MMR was 28.6 percent (95% CI: 11.3, 52.3), and the median duration of follow-up was 14.2 months (range 1.1, 26.3 months).
For pediatric patients with resistant/intolerant CP Ph+ CML, the major and complete cytogenetic responses were 82.1 percent (95% CI: 63.1, 93.9) and 78.6 percent (95% CI: 59, 91.7), respectively. The MMR was 50 percent (95% CI: 30.6, 69.4). Among 14 patients who achieved MMR, two patients lost MMR after 13.6 and 24.7 months on treatment. The median follow-up was 23.2 months (range: 1, 61.5 months).
The most common adverse reactions in pediatric patients (>=20%) were diarrhea, abdominal pain, vomiting, nausea, rash, fatigue, hepatic dysfunction, headache, pyrexia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in pediatric patients (>=45%) were increased creatinine, increased alanine aminotransferase or aspartate aminotransferase, decreased white blood cell count, and decreased platelet count.
The recommended bosutinib dose for pediatric patients with newly diagnosed CP Ph+ CML is 300 mg/m2 orally once daily with food and the recommended dosage for pediatric patients with resistant/intolerant CP Ph+ CML is 400 mg/m2 orally once daily with food. For patients who are unable to swallow capsules, the contents of the capsules can be mixed with applesauce or yogurt.
Fast Track Designation of MYTX-011 for NSCLC With cMET Overexpression
The FDA has granted Fast Track designation to MYTX-011, an investigational cMET-targeting ADC for the treatment of patients with non-small cell lung cancer (NSCLC) with cMET overexpression. This designation encompasses NSCLC patients with any level of cMET overexpression, including low and intermediate.
Fast Track designation is intended to aid the development and expedite the review of drugs to treat serious and life-threatening conditions with unmet medical needs, with the goal of reaching patients earlier. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the therapeutic candidate's clinical trial designs and development plans.
"While a small fraction of NSCLC tumors highly express cMET, a much broader patient population has tumors which overexpress cMET, but at lower levels," said Rebecca Heist, MD, MPH, the KisMET-01 study investigator, Associate Professor of Medicine at Harvard Medical School, and the Lee Albright and Nile Albright MD Endowed Chair in Clinical Cancer Research at Massachusetts General Hospital. "It's important we continue investigating the potential of MYTX-011 for patients with NSCLC who need new approaches to treating their cancer as many either do not respond to or develop resistance to existing treatment options."
MYTX-011, an investigational cMET-targeting ADC, leverages innovative technology designed to allow ADCs to actively navigate inside of cells, potentially increasing the delivery of anti-cancer agents to tumor cells with less impact on healthy cells. This breakthrough approach takes the next step beyond linker-payload technologies and is designed to improve ADC efficacy against a broad set of molecular targets and patient profiles. MYTX-011 is currently being evaluated in the Phase I1 KisMET-01 clinical trial, a first-in-human, open-label, multi-center, dose-escalation, and dose-expansion study enrolling patients with locally advanced, recurrent, or metastatic NSCLC (NCT05652868).
Momelotinib Approved for Myelofibrosis Patients With Anemia
Momelotinib has been approved by the FDA for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia) in adults with anemia. Momelotinib is a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. To date, it is the only approved medicine for both newly diagnosed and previously treated myelofibrosis patients with anemia that addresses the key manifestations of the disease-namely anemia, constitutional symptoms, and splenomegaly.
Myelofibrosis is a blood cancer affecting approximately 25,000 patients in the U.S. It can lead to severely low blood counts, including anemia and thrombocytopenia; constitutional symptoms such as fatigue, night sweats, and bone pain; and splenomegaly. About 40 percent of patients have moderate-to-severe anemia at the time of diagnosis, and nearly all patients are estimated to develop anemia over the course of the disease. Physicians have had limited treatment options to treat myelofibrosis patients with anemia. These patients often require transfusions and more than 30 percent will discontinue treatment due to anemia. Patients who are transfusion-dependent have a poor prognosis and shortened survival.
"With momelotinib we have the potential to establish a new standard of care for myelofibrosis patients with anemia," noted Ruben A. Mesa, MD, FACP, President and Executive Director of Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center. "Addressing key manifestations of myelofibrosis, including anemia, constitutional symptoms, and splenomegaly, makes a significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease."
The FDA approval of momelotinib is supported by data from the pivotal MOMENTUM study and a subpopulation of adult patients with anemia from the SIMPLIFY-1 phase III trial. MOMENTUM was designed to evaluate the safety and efficacy of momelotinib versus danazol for the treatment and reduction of key manifestations of myelofibrosis in an anemic, symptomatic, JAK inhibitor-experienced population.
The MOMENTUM trial met all its primary and key secondary endpoints, demonstrating statistically significant response with respect to constitutional symptoms, splenic response, and transfusion independence in patients treated with momelotinib versus danazol. SIMPLIFY-1 was designed to evaluate the efficacy and safety of momelotinib versus ruxolitinib in myelofibrosis patients who had not received a prior JAK-inhibitor therapy. Safety and efficacy results for SIMPLIFY-1 were based on a subset of patients with anemia. In these clinical trials, the most common adverse reactions were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.