On June 15, 2024 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported detailed results from the global Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent (NTD) alpha- or beta-thalassemia in a plenary session (abstract #S104) at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 (EHA2024) Hybrid Congress, which is being held June 13-16, 2024, in Madrid, Spain (Press release, Agios Pharmaceuticals, JUN 15, 2024, View Source [SID1234644352]). In a related poster presentation (abstract #P1529), the company presented additional data from the ENERGIZE study highlighting clinically meaningful improvements in health-related quality of life measures and patient-reported outcomes among patients in the mitapivat arm compared to those in the placebo arm.

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The ENERGIZE study achieved its primary endpoint, with mitapivat demonstrating a statistically significant increase in hemoglobin response rate compared to placebo. Statistical significance was also achieved for both key secondary endpoints associated with change from baseline in FACIT-Fatigue Score and hemoglobin concentration. These improvements were observed across all pre-specified subgroups.

"The data from the ENERGIZE study are compelling, with mitapivat-treated patients achieving meaningful improvements in non-transfusion-dependent thalassemia’s hallmark symptom of anemia as well as in key measures of how patients feel and function," said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. "Together with the recently announced positive results from the ENERGIZE-T study of mitapivat in adults with transfusion-dependent thalassemia, the detailed ENERGIZE results underscore mitapivat’s potential to become an important treatment option for all subtypes of thalassemia – alpha- and beta-thalassemia, transfusion-dependent and non-transfusion-dependent – with the convenience of a pill. We look forward to working with regulators as we anticipate filing for approval in the U.S. by the end of this year."

"I am pleased to present the results of the ENERGIZE study to my esteemed colleagues and believe they will share my enthusiasm for the positive impact mitapivat may have for patients with non-transfusion-dependent alpha- or beta-thalassemia," said Ali Taher, M.D., Ph.D., Professor of Medicine, Hematology & Oncology and Director – Naef K. Basile Cancer Institute, American University of Beirut Medical Center in Beirut, Lebanon; an investigator in the ENERGIZE study. "Globally, there are currently no approved oral treatments for non-transfusion-dependent thalassemia, which is characterized by anemia, ineffective erythropoiesis, hemolysis and iron overload and can cause severe complications, reduced quality of life and shortened lifespan. Based on the data collected in the ENERGIZE study, mitapivat has the potential to become a foundational treatment for non-transfusion-dependent thalassemia."

"The ENERGIZE data presented at this congress show that non-transfusion-dependent alpha- or beta-thalassemia patients treated with mitapivat experienced clinically meaningful improvements in fatigue and walking capacity, as well as improvements in patient-reported outcomes across a range of disease symptoms," said Kevin Kuo, M.D., MSc, FRCPC; Division of Hematology, University of Toronto in Ontario, Canada; an investigator in the ENERGIZE study. "There is a tremendous need for oral therapies that can improve how people with thalassemia feel and function and reduce the impact of the disease on their lives. Patients with alpha- or beta-thalassemia, regardless of transfusion status, frequently report negative effects on daily activities and physical functioning. On a number of domains of health-related quality of life, adults with non-transfusion-dependent thalassemia experience even greater symptom burden than their transfusion-dependent counterparts. I am excited about the potential of mitapivat to support quality of life improvements for these individuals."

Agios also recently announced positive results from the Phase 3 ENERGIZE-T study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia. The company intends to file for regulatory approval of mitapivat as a treatment for thalassemia by the end of 2024, incorporating all available data from both studies.

Results for the Phase 3 ENERGIZE study were as follows:

A total of 194 patients were enrolled in the study, with 130 randomized to mitapivat 100 mg twice-daily (BID) and 64 randomized to matched placebo. 122 (93.8%) in the mitapivat arm and 62 (96.9%) in the placebo arm completed the 24-week double-blind period of the study.
Baseline demographics and characteristics were balanced between mitapivat and placebo arms, and representative of a population of non-transfusion dependent thalassemia patients.
The study met the primary endpoint of hemoglobin response. Hemoglobin response was defined as an increase of ≥1 g/dL in average hemoglobin concentrations from week 12 through week 24 compared with baseline.
42.3% (n=55/130) of patients in the mitapivat arm achieved a hemoglobin response, compared to 1.6% (n=1/64) of patients in the placebo arm (2-sided p<0.0001).
Among patients who achieved hemoglobin response in the mitapivat arm, the mean change from baseline in average hemoglobin concentration from week 12 to 24 was 1.56 g/dL.
Hemoglobin response rates were higher among those treated with mitapivat compared to placebo across all prespecified subgroups, including:
Thalassemia genotype: 23.8% (n=10/42) of alpha-thalassemia patients in the mitapivat arm achieved a hemoglobin response, compared to no alpha-thalassemia patients in the placebo arm. 51.1% (n=45/88) of beta-thalassemia patients in the mitapivat arm achieved a hemoglobin response, compared to 2.3% (n=1/44) of beta-thalassemia patients in the placebo arm.
Baseline hemoglobin concentration: 47.4% (n=45/95) of patients whose baseline hemoglobin concentration was ≤9.0 g/dL in the mitapivat arm achieved a hemoglobin response, compared to 2.1% (n=1/47) of patients in the placebo arm. 28.6% (n=10/35) of patients whose baseline hemoglobin concentration was between 9.1 and 10.0 g/dL achieved a hemoglobin response, compared to no patients in the placebo arm.
Treatment with mitapivat also demonstrated statistically significant improvements compared to placebo for both key secondary endpoints:
The average change from baseline (95% confidence interval) in FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) subscale score from week 12 to week 24 was 4.85 (3.41, 6.30) in the mitapivat arm compared to 1.46 (–0.43, 3.34) in the placebo arm (p=0.0026).
The average change from baseline (95% confidence interval) in average hemoglobin concentration from week 12 to week 24 was 0.86 (0.73, 0.99) g/dL in the mitapivat arm compared to –0.11 (–0.28, 0.07) g/dL in the placebo arm (p<0.0001).
Improvements were observed in patients treated with mitapivat across measures of health-related quality-of-life, including the six-minute walk test and the Patient Global Impression of Change (PGIC) fatigue, walking capacity, and thalassemia symptoms subscales.
Six-minute walk test: The average change (95% confidence interval) from baseline to week 24 was 30.48 (19.31, 41.64) meters in the mitapivat arm compared to 7.11 (–7.39, 21.62) in the placebo arm.
PGIC: A higher proportion of patients in the mitapivat arm reported improvements in fatigue as per PGIC versus those in the placebo arm at weeks 12, 16, 20, and 24. A higher proportion of patients in the mitapivat arm reported improvements in thalassemia symptoms and walking capacity as per PGIC at week 24 versus those in the placebo arm.
Overall, during the 24-week double-blind period, incidence of adverse events was similar across mitapivat and placebo arms, with 82.9% (n=107) of patients in the mitapivat arm and 79.4% (n=50) of patients in the placebo arm experiencing treatment-emergent adverse events (TEAEs).
The most frequently reported TEAEs were headache, initial insomnia, nausea and upper respiratory tract infection.
3.9% (n=5) of patients in the mitapivat arm experienced Grade ≥3 treatment-related TEAEs. There were no serious TEAEs.
3.1% (n=4) of patients in the mitapivat arm experienced TEAEs leading to discontinuation; there were no TEAEs leading to discontinuation in the placebo arm.
Conference Call Information
Agios will host a virtual investor breakout session tomorrow, June 16, 2024, at 10:00 a.m. ET (4 p.m. CEST) to review the key clinical oral and poster presentations from the EHA (Free EHA Whitepaper)2024 meeting. The event will be webcast live and can be accessed under "Events & Presentations" in the Investors and Media section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

About PYRUKYND (mitapivat)
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.

IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

Drug Interactions:

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information and Summary of Product Characteristics for PYRUKYND.

On June 15, 2024 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported statistically significant and clinically meaningful results from its Phase III STARGLO study of Columvi (glofitamab-gxbm) in combination with gemcitabine and oxaliplatin (GemOx) versus Rituxan (rituximab) in combination with GemOx (R-GemOx) for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy (Press release, Genentech, JUN 15, 2024, View Source [SID1234644356]). Data were featured in the congress Press Briefing and presented today in the Plenary Abstracts Session at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress as a late-breaking oral presentation.

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"The results from STARGLO are the first to show the potential of a CD20xCD3 bispecific antibody to make a difference in second or later-line DLBCL in people who are ineligible for transplant and have limited options," said Jeremy Abramson, M.D., director, Jon and Jo Ann Hagler Center for Lymphoma at the Massachusetts General Hospital Cancer Center, and principal investigator of the STARGLO study. "Glofitamab in combination with GemOx showed clinically significant improvement in overall survival, as well as key secondary endpoints, and the benefits were reinforced with an additional 11 months of follow-up."

The primary analysis (median follow-up of 11.3 months) confirmed that the study met its primary endpoint of overall survival (OS), demonstrating that patients treated with Columvi plus GemOx lived significantly longer, with a 41% reduction in the risk of death (hazard ratio [HR]=0.59, 95% CI: 0.40-0.89, p=0.011) versus R-GemOx. Median OS was not reached with the Columvi regimen versus nine months for R-GemOx. Safety of the combination appeared consistent with the known safety profiles of the individual medicines.

Pre-specified exploratory subgroup analyses showed comparable results, including consistency across the clinically relevant stratification factors of line of therapy (second-line versus third-line+) and outcome of last therapy (relapsed versus refractory). Regional inconsistencies were observed, however interpretation is limited given the exploratory nature of these analyses and small subgroups with wide confidence intervals.

"This marks a first step in advancing Columvi combinations in earlier settings to address the urgent need for the 40% of people who will relapse or have refractory disease and who have limited options," said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. "Moreover, patients do not have to wait to start treatment with Columvi. This could be particularly important for patients with highly aggressive disease who are at risk of rapid disease progression."

The Columvi combination also met its key secondary endpoints, with a 63% reduction in risk of disease worsening or death (progression-free survival, PFS) compared to R-GemOx (HR=0.37; 95% CI: 0.25–0.55, p<0.0001). A follow-up analysis was conducted after all patients had completed therapy (median follow-up of 20.7 months), which showed continued benefit in both primary and secondary endpoints. Median OS for people treated with the Columvi combination was 25.5 months, nearly double what was seen for people treated with R-GemOx at 12.9 months, and more than twice as many patients experienced a complete response (58.5% versus 25.3%, respectively).

Adverse event (AE) rates were higher with the Columvi combination versus R-GemOx, noting higher median number of cycles received with Columvi combination (11 versus 4). One of the most common AEs was cytokine release syndrome, which was generally low grade (Any Grade: 44.2%, Grade 1: 31.4%, Grade 2: 10.5%, Grade 3: 2.3%) and occurred primarily in Cycle 1.

Columvi is the first CD20xCD3 bispecific antibody to demonstrate a survival benefit in DLBCL in a randomized Phase III trial, demonstrating the potential of this type of therapeutic combination to improve survival outcomes in earlier lines of treatment. The standard second-line therapy for R/R DLBCL patients has historically been high-dose chemotherapy followed by stem-cell transplant, however, not everyone with R/R DLBCL is a candidate due to age or coexisting medical conditions. Newer therapies are also becoming available, but barriers remain for many, and alternative treatment options are needed for these patients. Columvi is given as a fixed-duration treatment, offering people with R/R DLBCL a treatment end date and the possibility of a treatment-free period, unlike continuous treatments.

Results from the STARGLO study will be submitted to global health authorities, including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency.

Columvi is also being investigated in other aggressive, hard-to-treat lymphomas and was recently granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with relapsed or refractory mantle cell lymphoma who have received at least two prior therapies based on results from the Phase I/II NP30179 study.

About the STARGLO Study

The STARGLO study [GO41944; NCT04408638] is a Phase III, multicenter, open-label, randomized study evaluating the efficacy and safety of Columvi (glofitamab-gxbm) in combination with gemcitabine plus oxaliplatin (GemOx) versus Rituxan (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability.

STARGLO is intended as a confirmatory study to convert Columvi’s accelerated approval in the U.S. and conditional marketing authorization in the EU to full approvals for people with R/R DLBCL after two or more lines of systemic therapy based on the pivotal Phase I/II NP30179 study.

About Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma (NHL) in the U.S. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes. DLBCL not otherwise specified is the most common category of large B-cell lymphoma (LBCL) and accounts for about 80% or more of cases. It applies to cases that do not fall into any specific disease subgroups of LBCL.

About Columvi (glofitamab-gxbm)
Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. A clinical development program for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

Columvi U.S. Indication

Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.

It is not known if Columvi is safe and effective in children.

The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Columvi?

Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.

Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:

fever of 100.4°F (38°C) or higher
chills or shaking
fast or irregular heartbeat
dizziness or light-headedness
trouble breathing
shortness of breath
Due to the risk of CRS, you will receive Columvi on a "step-up dosing schedule".

A single dose of a medicine called obinutuzumab will be given to you on the first day of your first treatment cycle (Day 1 of Cycle 1).
You will start the Columvi step-up dosing schedule a week after the obinutuzumab dose. The step-up dosing schedule is when you receive smaller "step-up" doses of Columvi on Day 8 and Day 15 of Cycle 1. This is to help reduce your risk of CRS. You should be hospitalized during your infusion and for 24 hours after receiving the first step-up dose on Day 8. You should be hospitalized during your infusion and for 24 hours after receiving the second step-up dose on Day 15 if you experienced CRS during the first step-up dose.
You will receive your first full dose of Columvi a week after the second step-up dose (this will be Day 1 of Cycle 2).
If your dose of Columvi is delayed for any reason, you may need to repeat the "step-up dosing schedule".
If you had more than mild CRS with your previous dose of Columvi, you should be hospitalized during and for 24 hours after receiving your next dose of Columvi.
Before each dose of Columvi, you will receive medicines to help reduce your risk of CRS and infusion-related reactions.
Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.

Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.

What are the possible side effects of Columvi?

Columvi may cause serious side effects, including:

Cytokine Release Syndrome.
Neurologic problems. Columvi can cause serious neurologic problems that may lead to death. Your healthcare provider will monitor you for neurologic problems during treatment with Columvi. Your healthcare provider may also refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any signs or symptoms of neurologic problems, including:
headache
confusion and disorientation
difficulty paying attention or understanding things
trouble speaking
sleepiness
memory problems
numbness, tingling, or weakness of the hands or feet
dizziness
shaking (tremors)
Serious Infections. Columvi can cause serious infections that may lead to death. Your healthcare provider will monitor you for signs and symptoms of infection and treat you as needed. Tell your healthcare provider right away if you develop any signs of an infection, including: fever, chills, weakness, cough, shortness of breath, or sore throat.
Growth in your tumor or worsening of tumor related problems (tumor flare). Tell your healthcare provider if you get any of these signs or symptoms of tumor flare:
tender or swollen lymph nodes
pain or swelling at the site of the tumor
chest pain
cough
trouble breathing
The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.

The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).

Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.

Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
have kidney problems
are pregnant or plan to become pregnant. Columvi may harm your unborn baby
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with Columvi.
You should use effective birth control (contraception) during treatment and for 1 month after your last dose of Columvi. Talk to your healthcare provider about what birth control method is right for you during this time.
Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with Columvi.
are breastfeeding or plan to breastfeed. Columvi may pass into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of Columvi.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Columvi?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.

You may report side effects to the FDA at (800) FDA-1088 or View Source You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit View Source

On June 14, 2024 Pfizer Inc. (NYSE: PFE) reported detailed overall survival (OS) results from the Phase 2 MagnetisMM-3 study of ELREXFIO (elranatamab-bcmm) in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) (Press release, Seagen, JUN 14, 2024, View Source [SID1234644338]). The study demonstrated a median OS of 24.6 (95% CI, 13.4, NE) months in cohort A (n=123) of the pivotal single arm trial.

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These data from MagnetisMM-3 will be presented during a poster session (#932) at the European Hematology Association (EHA) (Free EHA Whitepaper) Hybrid Congress in Madrid, Spain, from June 13-16. Additional presentations at EHA (Free EHA Whitepaper) 2024 will highlight ELREXFIO data across the comprehensive MagnetisMM clinical trial program.

"These compelling overall survival data support the clinical benefit ELREXFIO has already demonstrated and its potential to be a transformative treatment option for people with multiple myeloma," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "The latest results from MagnetisMM-3 reinforce the very promising efficacy observed with ELREXFIO in a relapsed or refractory setting, with deep and durable responses and although definitive conclusions cannot be drawn across studies, the longest reported median progression-free survival among B-cell maturation antigen bispecific antibodies."

After more than two years of follow-up in the MagnetisMM-3 trial, the overall response rate (ORR) for patients on ELREXFIO was 61.0% (37.4% ≥complete response rate (CRR)), with responses deepening over time, and the median duration of response (DOR) was not reached. At two years, the estimated DOR rate was 66.9% (95% CI: 54.4, 76.7) for all responders, and 87.9% (95% CI: 73.1, 94.8) for patients with CR or better response. Median progression-free survival (PFS) was 17.2 months (95% CI: 9.8 months-NE). For patients with CR or better response, the median PFS was not reached, and at two years, the estimated PFS rate was 90.6% (95% CI: 76.9, 96.4).

"People with relapsed or refractory multiple myeloma often have limited therapeutic options as their disease progresses due to treatment resistance, resulting in increasingly shorter remission and duration of response," said MagnetisMM-3 clinical trial investigator Mohamad Mohty, M.D., Ph.D., Professor of Hematology and Head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France. "These impactful overall survival data are particularly encouraging given the very advanced patient population with characteristics associated with poorer outcomes."

The safety and tolerability of ELREXFIO in MagnetisMM-3 were consistent with what have been previously observed. Five patients (4.1%) experienced secondary primary malignancies (SPMs), all cases being squamous cell carcinoma of the skin, consistent with SPMs often observed in patients with multiple myeloma (MM), while no hematological SPMs were reported. Due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), patients should be monitored for signs and symptoms for 48 hours after administration of each of the two step-up doses within the ELREXFIO dosing schedule and instructed to remain in proximity of a healthcare facility. In the EU, precautionary hospitalization is not required. Patients are not required to stay near a healthcare facility for the 76 mg first treatment dose.

Based on results of the MagnetisMM-3 trial, ELREXFIO received accelerated approval in August 2023 from the U.S. Food and Drug Administration for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. Continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial. In December 2023, the European Commission granted conditional marketing authorization for ELREXFIO for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. ELREXFIO has also received approval in Switzerland, Brazil and Canada under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. Two other countries (Australia and Singapore) are participating in Project Orbis. The Medicines and Healthcare products Regulatory Agency (MHRA) granted ELREXFIO authorization for Great Britain for RRMM.

Pfizer’s comprehensive ongoing MagnetisMM clinical development program is investigating the use of elranatamab across the entire spectrum of patients with MM, from RRMM to newly diagnosed MM. Ongoing registrational-intent trials are comparing elranatamab to current standards of care both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-4 investigating elranatamab treatment with other anti-cancer therapies, MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, MagnetisMM-7 in newly diagnosed patients after transplant, and MagnetisMM-32 in patients with prior anti-CD38-directed therapy.

About MagnetisMM-3

MagnetisMM-3 is an open-label, multicenter, non-randomized Phase 2 study of ELREXFIO monotherapy in participants with multiple myeloma who are refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-cluster of differentiation 38 antibody. The study enrolled two cohorts of participants: one with and one without prior treatment with a B-cell maturation antigen-directed antibody-drug conjugate or chimeric antigen receptor T-cell therapy. Participants received subcutaneous ELREXFIO as two step-up priming doses followed by a weekly 76 mg injection. The primary endpoint is objective response rate as assessed by Blinded Independent Central Review (BICR). Key secondary endpoints include duration of response, progression-free survival, minimal residual disease negativity rate, overall survival, and safety. For more information about the trial, visit www.clinicaltrials.gov (NCT04649359).

About Multiple Myeloma

Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.1 MM is the second most common type of blood cancer, with over 50,000 new cases diagnosed annually in Europe and over 187,000 new cases diagnosed globally each year.2,3 About 40% of those diagnosed with MM won’t survive beyond five years,4 and most will receive 4 or more lines of therapy due to relapse.5 While disease trajectory varies for each person, relapses are nearly inevitable.6 The goal of therapy for people with relapsing or refractory MM is to achieve disease control with acceptable toxicity and improved quality of life.7

About ELREXFIO (elranatamab-bcmm)

ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-cluster of differentiation (CD)3-directed bispecific antibody immunotherapy that binds to BCMA on myeloma cells and CD3 on T cells, activating the T cells to kill myeloma cells.

U.S. INDICATION

ELREXFIO may cause side effects that are serious, life-threatening, or can lead to death, including cytokine release syndrome (CRS) and neurologic problems. CRS is common during treatment with ELREXFIO.

Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or neurologic problems, including:

fever of 100.4°F (38°C) or higher
trouble breathing
chills
dizziness or light-headedness
fast heartbeat
headache
increased liver enzymes in your blood
agitation, trouble staying awake, confusion or disorientation, or seeing or hearing things that are not real (hallucinations)
trouble speaking, thinking, remembering things, paying attention, or understanding things
problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms
numbness and tingling (feeling like "pins and needles")
burning, throbbing, or stabbing pain
changes in your handwriting
Due to the risk of CRS, you will receive ELREXFIO on a "step-up" dosing schedule and should be hospitalized for 48 hours after the first "step-up" dose and for 24 hours after the second "step-up" dose of ELREXFIO.

For your first dose, you will receive a smaller "step-up" dose of ELREXFIO on day 1
For your second dose, you will receive a larger "step-up" dose of ELREXFIO, which is usually given on day 4 of treatment
For your third dose, you will receive the first "treatment" dose of ELREXFIO, which is usually given on day 8
If your dose of ELREXFIO is delayed for any reason, you may need to repeat step-up dosing. Before each dose of ELREXFIO you receive during the step-up dosing schedule, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses.

ELREXFIO is available only through the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS) Program due to the risk of CRS and neurologic problems. You will receive an ELREXFIO Patient Wallet Card from your healthcare provider. Carry the ELREXFIO Patient Wallet Card with you at all times and show it to all of your healthcare providers. The ELREXFIO Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the ELREXFIO Patient Wallet Card. You may need to be treated in a hospital.

Before taking ELREXFIO, tell your healthcare provider about all of your medical conditions, including if you:

have an infection
are pregnant or plan to become pregnant. ELREXFIO may harm your unborn baby. Females who are able to become pregnant should do a pregnancy test before starting treatment with ELREXFIO and should use effective birth control during treatment and for four months after your last dose of ELREXFIO. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with ELREXFIO
are breastfeeding or plan to breastfeed. It is not known if ELREXFIO passes into your breast milk. Do not breastfeed during treatment and for four months after your last dose of ELREXFIO
Tell your healthcare provider about all of the medications you take, including prescription and over-the-counter medications, vitamins, and herbal supplements.

Do not drive, operate heavy or potentially dangerous machinery, or do other dangerous activities during treatment with ELREXFIO:

for 48 hours after completing each of the 2 doses of ELREXFIO that are part of the "step-up dosing schedule" and your first full treatment dose, and
at any time during treatment with ELREXFIO if you develop any new neurologic symptoms, such as dizziness, confusion, shaking (tremors), sleepiness, or any other symptom that impairs consciousness, until the symptoms go away
Infections: Upper respiratory tract infection and pneumonia are common during treatment with ELREXFIO. ELREXFIO can cause bacterial and viral infections that are severe, life-threatening, or that may lead to death.

Your healthcare provider may prescribe medications for you to help prevent infections and treat you as needed if you develop an infection during treatment with ELREXFIO
Tell your healthcare provider right away if you develop any signs or symptoms of an infection during treatment with ELREXFIO, including: fever of 100.4°F (38°C) or higher, chills, cough, shortness of breath, chest pain, sore throat, pain during urination, or feeling weak or generally unwell
People with active infections should not start ELREXFIO
Decreased white blood cell counts: Decreased white blood cell counts are common during treatment with ELREXFIO and can also be severe. A fever can occur with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will treat you as needed.

Liver problems: ELREXFIO can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Tell your healthcare provider if you develop any of the following signs or symptoms of a liver problem, including:

tiredness
loss of appetite
pain in your right upper stomach-area
dark urine
yellowing of your skin or the white part of your eyes
The most common side effects of ELREXFIO include:

tiredness
injection site reaction, such as redness, itching, pain, bruising, rash, swelling, and tenderness
diarrhea
muscle and bone pain
decreased appetite
rash
cough
nausea
fever
The most common severe abnormal lab test results with ELREXFIO include decreased white blood cells, red blood cells, and platelets.

Your healthcare provider may temporarily or permanently stop ELREXFIO if you have any of the side effects listed and they are severe. These are not all of the possible side effects of ELREXFIO.

Call your healthcare provider for medical advice about side effects. You may report side effects to the U.S. Food and Drug Administration (FDA) at 1-800-FDA-1088.

What is ELREXFIO?

ELREXFIO is a prescription medication used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment
ELREXFIO was approved based on patient responses and durability of response. There are ongoing studies to confirm its clinical benefit. It is not known if ELREXFIO is safe and effective in children.

Please read full Prescribing Information , including BOXED WARNING, for ELREXFIO.

On June 14, 2024 Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a clinical-stage biotechnology company pioneering the development of bifunctional fusion proteins as a potential new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, reported updated interim data from the Phase 1B dose expansion clinical trial of SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML patients (Press release, Shattuck Labs, JUN 14, 2024, View Source [SID1234644339]). These data are to be featured in a poster presentation on June 14, 2024 at 18:00 CEST, during the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"We are pleased to present additional data from our Phase 1B dose expansion clinical trial, which further supports our differentiated mechanism of action and underscores SL-172154’s emergence as the leading CD47 inhibitor in hematologic malignancies," said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. "This update shows that the rate of complete remission has improved since our last data release in December, with additional patients in both cohorts who continue to improve on therapy. As a result of these encouraging data, and our expectation of rapid enrollment and progress in our ongoing randomized, controlled cohort in HR-MDS, we are focusing our efforts on our opportunity in HR-MDS and TP53m AML. These are indications with high unmet need, limited competition, and potential for accelerated paths to approval."

Dr. Lini Pandite, MBChB, M.B.A., Chief Medical Officer of Shattuck added, "We are encouraged by the maturing data that continues to underscore the therapeutic potential, and manageable safety profile, of SL-172154 for patients with previously untreated HR-MDS and TP53m AML. Accumulating clinical evidence now shows the pharmacodynamic contribution of CD40 activation in the peripheral blood, and an emerging correlation between clinical remission and CD40 mediated induction of certain cytokines. The TP53m AML and HR-MDS patients we have treated represent a high-risk group with short duration of complete remission and overall survival when treated with azacitidine alone. Median overall survival and duration of remission have not yet been achieved, and we look forward to sharing additional durability data later this year. Enrollment is now underway for our randomized, controlled expansion cohort in frontline HR-MDS patients, and we expect to engage in regulatory discussions later this year regarding the registrational strategy for SL-172154."

A copy of the EHA (Free EHA Whitepaper) poster, titled "Phase 1b Study of SL-172154, a Bi-functional Fusion Protein Targeting CD47 and CD40, in Combination with Azacitidine (AZA) in Previously Untreated Acute Myeloid Leukemia (AML) and Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR- MDS) Patients (pts)," will be made available under posters in the Our Science section of Shattuck’s website.

Phase 1B Trial of SL-172154 in Frontline HR-MDS and TP53m AML

Key takeaways: Additional interim efficacy observed for SL-172154 in combination with AZA in frontline HR-MDS and TP53m AML.

•
HR-MDS: As of the data cut-off date of April 23, 2024, in 24 treated patients (21 had TP53m, 16 had complex karyotype, and seven had therapy-related MDS), the ORR was 67%.

•
Ten (42%) patients achieved a CR with 3.6 months as the median time to CR.

•
Nine patients are continuing on treatment (five CR, two mCR+HI, one SD+HI, one SD).

•
Three patients proceeded to allogeneic hematopoietic cell transplantation (HCT), all three patients achieved CR prior to HCT.

•
TP53m AML: As of the data cut-off date of June 4, 2024, in 21 treated patients (all 21 had TP53 mutations or deletion, 19 had a complex karyotype, and 14 had secondary AML) the ORR was 43%.

•
Six (29%) patients achieved a CR. One patient achieved a CRi and two patients achieved a partial remission (PR). The median time to CR was 3.8 months and none of the responders progressed as of the data cutoff.

•
Five responders (three CR, one CRi, one PR) were taken to HCT and seven patients were still undergoing treatment, including two patients in CR. Additional patients may be bridged to transplant in the coming months.

•
Preliminary analysis indicates clearance of TP53 mutation in four out of five TP53m HR-MDS patients and two out of four TP53m AML patients who achieved CR and were evaluated as of the data cutoff.

•
Median duration of response for OR and CR and overall survival had not yet been reached in either HR-MDS or TP53m AML as of the respective data cutoff dates.

Safety Results: As of the data cutoff date of April 23, 2024, SL-172154 showed a manageable safety profile: Infusion-related reactions (IRRs) were the most common SL-172154 treatment-emergent adverse events (TEAEs). There have been no G3 or higher IRRs when patients have been premedicated with dexamethasone. There was no evidence of hemolytic (destructive) anemia.

•
HR-MDS:

•
Grade 3/4 AEs were reported in ten (42%) patients as related/possibly related to SL-172154: IRR (n=3), febrile neutropenia (n=2), anemia, alkaline phosphate increased, chondrocalcinosis, colitis, cytokine release syndrome, decreased appetite, fatigue, hypertension, left ventricular dysfunction, myocardial infarction (MI), neutropenia, pancytopenia, thrombocytopenia, troponin I increase, each in one patient.

•
There was one death due to AE of sepsis, deemed unrelated to SL-172154, and three treatment discontinuations due to AEs, including MI (n=1), IRR (n=1) and sepsis (n=1)

•
As already reported in the Company’s May 2024 EHA (Free EHA Whitepaper) abstract, a Grade 4 MI occurred in one patient who first developed sepsis on-study. This patient had a history of coronary artery disease and type II diabetes. The MI occurred eight days after the last dose of SL-172154. Although reported by the investigator as possibly related, Shattuck’s assessment is that this event was unlikely related to SL-172154.

•
TP53m AML:

•
Grade 3/4 AEs were reported in seven patients (33%), as related/possibly related to SL-172154, including neutropenia (n=3), thrombocytopenia (n=2), leukopenia (n=2), ALT increased (n=1), AST increased (n=1), enterococcal bacteremia (n=1), fatigue (n=1), hypoxia (n=1) and pneumonia (n=1)

•
There were three deaths due to AEs deemed unrelated to SL-172154 including sepsis (n=1) and pneumonia (n=2)

•
As already reported in the Company’s December 2023 update for the ASH (Free ASH Whitepaper) Annual Meeting, a Grade 5 cardiac arrest occurred in one patient with a history of significant cardiovascular disease, prior MI, prior stenting, prior arrhythmia, hypokalemia in the setting of amiodarone, additional adverse risk factors and other comorbidities. Although reported by the investigator as possibly related, Shattuck’s assessment is that this event was unlikely related to SL-172154.

Key Takeaways from Phase 1B Trial of SL-172154 in Platinum-Resistant Ovarian Cancer (PROC)

SL-172154 in combination with pegylated liposomal doxorubicin (PLD) or mirvetuximab soravtansine (Elahere)

•
Interim efficacy results as of April 23, 2024, showed four of 21 (19%) treated patients in our Phase 1B study of SL-172154 in combination with PLD have achieved partial responses. The Javelin-200 study reported an ORR of 4% with PLD alone. Two additional patients with stable disease showed maximum tumor reductions of 17% and 27% and were continuing on study. The Company is continuing to follow patients for progression free survival and overall survival.

•
In our cohort combining SL-172154 with Elahere, the Company has completed enrollment. As of the April 23, 2024 data cutoff, the Company has not observed an ORR benefit beyond Elahere alone, and the Company plans to further follow patients for progression free survival and overall survival.

•
Both of these combinations, SL-172154 combined with PLD and SL-172154 combined with Elahere, have shown an acceptable safety profile with IRRs as the most common treatment emergent AE as of the data cutoff.

•
The Company is not currently planning to conduct additional clinical development in PROC, in part due to the evolving competitive landscape in this indication. Should progression free survival or overall survival mature favorably in either PROC cohort, we would evaluate further development in PROC at that time. Shattuck will focus all current later-stage clinical development efforts in AML and HR-MDS due to the strength of the emerging efficacy results in those patient populations, the limited competition, and the potential for these indications to be the fastest path to registration.

Conference Call at 7:30 a.m. ET Today

Shattuck will host a conference call today at 7:30 a.m. ET featuring lead investigator Dr. Naval Daver, MD, (Professor and the Director of the Leukemia Research Alliance Program in the Department of Leukemia and MD Anderson Cancer Center in Houston, TX) to discuss the data from the poster presentation featured at the EHA (Free EHA Whitepaper) 2024 Congress, including an interim safety and efficacy update from the frontline expansion cohorts in HR-MDS and TP53m AML. To listen to the live webcast, please visit the Investor Relations page of the Shattuck Labs website here. Participants may register for the call here. While not required, interested participants are encouraged to join 10 minutes prior to the start of the event.

A replay of the webcast will be available following the conclusion of the live call and will be accessible on the Company’s website.

About SL-172154

SL-172154 (SIRPα-Fc-CD40L) is an investigational Agonist Redirected Checkpoint (ARC) fusion protein designed to simultaneously inhibit the CD47/SIRPα checkpoint interaction and activate the CD40 costimulatory receptor to bolster an anti-tumor immune response in patients with advanced cancer. Multiple Phase 1 clinical trials are ongoing for patients with platinum-resistant ovarian cancer (NCT04406623, NCT05483933) and patients with AML and HR-MDS (NCT05275439).

On June 14, 2024 Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, reported updated data from multiple combination trials of revumenib, the Company’s potent, selective, small molecule menin inhibitor, in patients with acute leukemias (Press release, Syndax, JUN 14, 2024, View Source [SID1234644341]). The updated data are being presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Congress, being held June 13-16 in Madrid, Spain and virtually.

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"The growing body of data supports the potential for revumenib to have a meaningful impact in combination with current standard of care therapies," said Joshua F. Zeidner, M.D., Chief, Leukemia Research at the University of North Carolina, Lineberger Comprehensive Cancer Center. "Based on the BEAT AML data in the newly diagnosed setting which showed a high rate of MRD-negative responses coupled with a safety profile that enables combination use, revumenib has the potential to become a cornerstone of treatment as front-line therapy for newly diagnosed KMT2Ar and mNPM1 AML."

"We are committed to advancing revumenib across a spectrum of acute leukemia patients. As we prepare for the expected near-term approval of revumenib in the relapsed or refractory setting, we look forward to providing additional clinical data as monotherapy and in combination to support treatment in various acute leukemia treatment settings where novel treatment options are urgently needed," said Neil Gallagher, M.D., Ph.D., President, Head of Research and Development at Syndax.

BEAT AML Trial

The Company announced updated data from the BEAT AML trial of revumenib in combination with venetoclax/azacitidine in newly diagnosed mutant nucleophosmin (mNPM1) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) patients aged 60 years or older in an oral presentation titled "Phase 1b Study of Azacitidine, Venetoclax and Revumenib in Newly Diagnosed Older Adults with NPM1 Mutated or KMT2A Rearranged AML: Interim Results of Dose Escalation from the BeatAML Consortium."

The dose escalation phase of the trial tested revumenib at doses of 113 mg and 163 mg q12h in combination with a strong CYP3A4 inhibitor beginning on day 1 of a 28-day cycle in combination with on label doses of venetoclax and azacitidine. As of the data cutoff date of May 1, 2024, 26 newly diagnosed mNPM1 (n=17) or KMT2Ar (n=9) AML patients were enrolled. In the efficacy evaluable population, the composite complete remission1 (CRc) rate was 96% (23/24) and 92% (22/24) of patients also attained minimal residual disease (MRD) negative status as determined by central flow cytometry. Three patients proceeded to hematopoietic stem cell transplant (HSCT). The first cohort of patients treated in the trial, at 113 mg, had extended follow-up and an estimated 12-month survival of 100%.

Revumenib was dosed safely at both the 113 mg and 163 mg q12h dose in combination with venetoclax and azacitidine. 15% (4/26) of patients experienced differentiation syndrome with one (4%) Grade 3 event. 46% (12/26) of patients experienced QTc prolongation with three (12%) Grade 3 events. All DS and QTc prolongations were self-limiting and resolved without complication or the need for revumenib dose reductions. Venetoclax was dosed in accordance with its label and an analysis of the onset and extent of hematologic toxicities suggest a similar experience to what has been reported for the venetoclax/azacytidine doublet. Overall, there were no new or increased safety signals observed when revumenib was added to this triplet combination.

An expansion cohort is ongoing at both dose levels to establish the recommended dose for future trials. The Company plans to initiate a pivotal trial with this combination in front-line newly diagnosed patients by year-end 2024.

AUGMENT-102 Trial

The Company also announced a poster presentation featuring updated data from the AUGMENT-102 trial of revumenib in combination with fludarabine/cytarabine in a predominantly pediatric population of patients with relapsed/refractory (R/R) mNPM1 (n=2), NUP98-rearranged (NUP98r) (n=1) or KMT2Ar (n=23) AML titled "Safety and Activity of Revumenib in Combination with Fludarabine/Cytarabine (FLA) in Patients with Relapsed/Refractory Acute Leukemias."

As of the data cutoff date of January 15, 2024, 27 patients received revumenib plus FLA, including 9 patients treated at 113 mg q12h and 18 treated at 163 mg q12h. The patients enrolled had a median age of 6 years and had received a median of 3 prior lines of therapy. Eighteen (67%) patients had prior FLA containing regimens while 11 (41%) patients had prior HSCT. Five (56%) patients treated at the 113 mg q12h dose and nine (50%) patients treated at the 163 mg q12h achieved a CRc. Most patients who achieved a CRc and had evaluable data achieved (MRD) negative status (10/14; 71%) and 7 patients underwent HSCT while in remission following treatment.

Overall, revumenib was tolerable in heavily pretreated patients with KMT2Ar, NUP98r, or NPM1m acute leukemias without increased frequency or severity of AEs compared with historic FLA data or revumenib monotherapy. One DLT occurred at the 163 mg q12h dose that was a Grade 4 decreased neutrophil count in a patient with multiple prior transplants.

Grade 3 and above adverse events in over 40% of patients included decreased platelet count (17/27; 63%), anemia (15/27; 56%) and febrile neutropenia (13/27; 48%). Lower rates of cytopenias were reported at the 163 mg q12h dose than the 113 mg q12h dose, consistent with faster remission at the higher dose. Lower rates of nonhematologic adverse events were also observed at the higher dose level, which further suggests that the adverse event profile was not driven by revumenib. There was one adverse event leading to death (sepsis at the 113 mg q12h dose level) not related to revumenib. There were no cases of differentiation syndrome in the trial.

This study supports the selection of revumenib 163 mg q12h (95 mg/m2 q12h if weight <40 kg) combined with FLA and a strong cytochrome P450 inhibitor as the RP2D, in line with the dose of revumenib under FDA review as a monotherapy agent.

Additional Presentations at EHA (Free EHA Whitepaper) 2024

In addition to updated results from the BEAT AML and AUGMENT-102 studies, an encore presentation of results from the pivotal AUGMENT-101 study of revumenib in R/R KMT2Ar acute leukemia were also featured at the Congress during an oral session titled "Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results from the Pivotal AUGMENT-101 Phase 2 Study."

Results from an exploratory analysis of immunophenotypic changes in AML blasts following treatment with revumenib were also featured in a poster presentation titled "Characterization of Immunophenotypic Changes Following Menin Inhibition in Acute Myeloid Leukemia."

Copies of EHA (Free EHA Whitepaper) posters and presentations will be available in the Publications and Meeting Presentations section of Syndax’s website.

About Revumenib

Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged (KMT2Ar), also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and mutant nucleophosmin (mNPM1) AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.