Juvenile Myelomonocytic Leukemia

On May 20, 2022, the Food and Drug Administration approved azacitidine (Vidaza, Celgene Corp.) for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia (JMML). Efficacy was evaluated in AZA-JMML-001 (NCT02447666), an international, multicenter, open-label study to evaluate the pharmacokinetics, pharmacodynamics, safety, and activity of azacitidine prior to hematopoietic stem cell transplantation (HSCT) in 18 pediatric patients with JMML. Patients were treated with intravenous azacitidine daily on Days 1-7 of a 28-day cycle for a minimum of 3 cycles and a maximum of 6 cycles, provided patients did not have disease progression or were ready for HSCT between Cycles 4 and 6. The main efficacy outcome measures were clinical complete remission (cCR) or clinical partial remission (cPR) according to the International JMML response criteria at 3 months (Cycle 3, Day 28). Responses must have been sustained for at least 4 weeks either in the 4-week period preceding or succeeding Cycle 3, Day 28. A total of 9 patients (50%, 95% CI: 26, 74) had confirmed clinical responses. Of these 9 patients, there were 3 cCR and 6 cPR. The median time to response was 1.2 months (range 0.95-1.87 months). The proportion of patients undergoing HSCT was 94% and the median time to HSCT was 4.6 months (range 2.8-19 months). Most common adverse reactions (>30%) occurring in pediatric patients with JMML were pyrexia, rash, upper respiratory tract infection, and anemia. The recommended dose for patients 1 month to less than 1 year of age or weighing less than 10 kg is 2.5 mg/kg. The recommended dose for patients ≥ age 1 and weighing ≥ 10 kg is 75 mg/m2. View full prescribing information for Vidaza. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date. This application was granted priority review, breakthrough designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer. Content current as of: 05/20/2022 Regulated Product(s) Drugs 05/20/2022 Drugs Resources for Information | Approved Drugs Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description Oncology (Cancer)/Hematologic Malignancies Approval Notifications Ongoing | Cancer Accelerated Approvals Verified Clinical Benefit | Cancer Accelerated Approvals Withdrawn | Cancer Accelerated Approvals Other | Cancer Accelerated Approvals Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description

TUESDAY, June 18, 2024 -- For children with relapsed or refractory juvenile myelomonocytic leukemia (JMML), trametinib is safe and effective, according to a study published online June 12 in Cancer Discovery . Noting that patients with relapsed or refractory (advanced) JMML have poor outcomes, Elliot Stieglitz, M.D., from the University of California San Francisco, and colleagues examined the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in a phase 2 trial involving 10 patients with advanced JMML. The researchers found that the objective response rate was 50 percent. After receiving trametinib, four patients with refractory disease proceeded to hematopoietic stem cell transplantation (HSCT). Three additional patients completed all 12 cycles of trametinib permitted in the study and then received trametinib off-protocol, without undergoing HSCT. The remaining three patients had progressive disease; by the end of cycle 2, two of these patients had molecular evolution. "Our trial offered an option for parents who did not want to subject their children to a repeat HSCT and, in some cases, helped patients avoid HSCT entirely," Stieglitz said in a statement. "The findings suggest that trametinib may be a less toxic alternative to HSCT for select patients." Two authors disclosed ties to the biopharmaceutical industry; Novartis provided trametinib for the study.

– Article Published in November 9th Issue of ASCO’s Journal of Clinical Oncology Precision Oncology (JCO PO) – – Results highlight PPMP as a tool for identifying most promising drug combinations for patients in high unmet medical needs, including JMML – FOSTER CITY, Calif., Nov. 09, 2023 (GLOBE NEWSWIRE) -- Notable Labs, Inc. (“Notable”) (Nasdaq: NTBL), a clinical stage therapeutic platform company developing predictive precision medicines for cancer patients, today announced the publication of data from an ex vivo study demonstrating the potential for its Predictive Precision Medicine Platform (PPMP) to identify more effective pre-hematopoietic stem cell transplantation (pre-HSCT) regimens for the treatment of juvenile myelomonocytic leukemia (JMML) in the November 9th Issue of the American Society of Clinical Oncology (ASCO) Journal JCO Precision Oncology. Part of this data was recently presented at the European Hematology Association (EHA) Hybrid Congress held in Frankfurt, Germany on June 8 – 15, 2023. Details of that presentation can be found on the Company’s website at https://notablelabs.com/. JMML is a rare, aggressive pediatric malignancy for which curative treatment is restricted to hematopoietic stem cell transplantation. Pre-HSCT therapies, i.e., therapies prior to transplantation, include moderately intensive chemotherapy (particularly fludarabine and cytarabine in combination (FLA)) and azacytidine (AZA) monotherapy. Unfortunately, in many cases, neither FLA nor AZA effectively eliminates the malignant cells and patients proceed to transplant with active disease. Applying its proprietary PPMP technology to blood or bone marrow samples from JMML patients, Notable screened 130 drug combinations and discovered that 27 of these combinations (26 dual-, 1 triple-combination) were more effective ex vivo than the components of these combinations tested individually. Of particular interest, investigators found that tretinoin (all-trans retinoic acid), a drug used as a standard-of-care agent in acute promyelocytic leukemia (APL), specifically enhanced the ex vivo effects of FLA and AZA. In addition to lowering the numbers of cells surviving FLA or AZA treatment, tretinoin, interestingly, also induced the cell surface expression of CD38, suggesting a potential rationale for use of CD38-targeting agents to further enhance the envisioned treatment effect. By identifying a superior combination effect with tretinoin, this research study identified potentially more effective pre-HCST regimens than those currently in use in JMML. “Publication in this prestigious, peer-reviewed journal not only highlights the profound need for better JMML treatment outcomes, but it further speaks to the powerful utility of Notable’s PPMP predicting treatment outcome, as demonstrated for other diseases,” said Thomas Bock, M.D., Chief Executive Officer of Notable. “In addition to identifying potentially more effective pre-HSCT drug combinations, these data may also serve as a valuable database for researchers and physicians by detailing the ex vivo effects of 130 drug combinations on JMML leukemic cells to prioritize therapeutic regimens for future clinical study and advance the standard of care.” The research article, titled “Tretinoin Enhances the Effects of Chemotherapy in Juvenile Myelomonocytic Leukemia Using an Ex Vivo Drug Sensitivity Assay” was first-authored by Dr. Elliot Stieglitz, M.D., Associate Professor at UCSF Benioff Children’s Hospital (UCSF, https://profiles.ucsf.edu/elliot.Stieglitz). “This publication marks the culmination of a multi-year collaboration between UCSF and Notable Labs,” remarked Dr. Stieglitz. “The ex vivo study described in the research article represents the largest high-throughput drug screen using primary samples conducted to date in this rare disease and will serve as a blueprint for researchers trying to bring novel combinations of medications to the clinic.” About Notable Labs, Inc. Notable Labs, Inc. is a clinical-stage platform therapeutics company developing predictive precision medicines for patients with cancer. Through its proprietary Predictive Precision Medicines Platform (“PPMP”), Notable bio- simulates a cancer treatment and predicts whether or not a patient is likely to respond to that specific therapeutic. Notable’s PPMP can identify and select clinically responsive patients prior to their treatment and thus fast-track clinical development in this patient population. By continually advancing and expanding the reach of the PPMP across diseases and predicted medical outcomes, Notable aims to be the leader in precision medicine and revolutionize the way in which patients seek and receive treatments that work best for them – patient by patient and cancer by cancer. Notable believes it has created a targeted and de-risked in-licensing strategy to deliver a product’s medical impact and commercial value faster, higher, and with a greater likelihood of success than traditional drug development. By transforming historical standards of care, Notable aims to create dramatic positive impact for patients and the healthcare community. Notable is headquartered in Foster City, California. Learn more at www.notablelabs.com and follow us @notablelabs. CONTACTS: Investor Relations: Daniel Ferry, LifeSci Advisors +1 (617) 430-7576, daniel@lifesciadvisors.com