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 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 14, 2024, Evopoint Biosciences Co., Ltd. (here in after referred to as Evopoint or "the company") reported that XNW27, a new-generationAntibody-Coupled Drug (ADC) developed by the company, has been granted FastTrack Designation (FTD) status by the FDA for the treatment of gastric cancer (Press release, Evopoint Biosciences, JUN 14, 2024, View Source [SID1234656285]). This designation will provide fast-track approvals for XNW’s global developmentand signifies the FDA’s recognition of the product’s excellent efficacy inpreclinical trials.

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Fast Track Designation (FTD) is one of the FDA’s accelerated drug review processes designed to facilitatethe development and expedite the review process of drugs for serious diseases tobetter fulfill medical needs. By obtaining FTD for a drug, a company developinga new drug will have more opportunities to communicate with the FDA during thesubsequent development and review process. In addition, the company can submitrolling submissions to the FDA when submitting New Drug Application/BiologicsLicense Application (NDA/BLA). These prioritized policies provide a strongguarantee to accelerate the development of new drugs.

About XNW27
XNW27 is a new-generation Antibody-Coupled Drug (ADC) targeting Claudin 18.2. It hasshown promising anti-tumor efficacies in preclinical and clinical trials, andmay offer a new therapeutic modality for patients with Claudin 18.2-expressingsolid tumors. In several solid tumor indications (including gastric cancer andpancreatic cancer, etc.), the study demonstrated good anti-tumor activity inboth low and high Claudin18.2-expressing pharmacological models and patients,with a favorable and manageable safety profile overall.

About Claudin18.2
Claudin18.2is a family of integrin membrane proteins found in epithelial and endothelialtight junctions, discovered by Shorichiro Tsukita et al. in 1998. There are 27members of this family with four transmembrane structural domains that areinvolved in the regulation of paracellular permeability and conductance. The expression profiles of different Claudin proteins in normal tissues vary. Claudin18 gene has two protein iso forms, Claudin18.1 and Claudin18.2. Claudin 18.1 isexpressed only in normal lungs, while Claudin18.2 is specifically expressed indifferentiated gastric mucosal epithelial cells. However, Claudin18.2 isabnormally expressed in many cancer abnormalities, including gastric cancer,pancreatic ductal adenocarcinoma, esophageal cancer, ovarian cancer, lungcancer, colon cancer, and biliary tract cancer, with its expression ratereaches over 50% in gastric cancer and pancreatic cancer. This feature makesClaudin18.2 an ideal target for the immunotherapy of solid tumors.

On June 14, 2024 Galapagos NV (Euronext & NASDAQ: GLPG) reported that it will present encouraging new data from the ongoing Phase 1/2 ATALANTA-1 study of CD19 CAR-T candidate, GLPG5101, in relapsed/refractory non-Hodgkin lymphoma (R/R NHL) at the annual European Hematology Association (EHA) (Free EHA Whitepaper) 2024 Hybrid Congress (Press release, Galapagos, JUN 14, 2024, View Source [SID1234644384]). Galapagos’ product candidate GLPG5101 is produced using the company’s innovative, decentralized T-cell manufacturing platform.

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The oral presentation includes updated safety and efficacy data for GLPG5101 in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). The presentation also includes durability and cellular kinetics data. At the data cut-off date of December 20, 2023, no unexpected safety findings were observed and treatment with GLPG5101 resulted in high complete response rates in all indications in this heavily pretreated patient population.

GLPG5101 was administered as a fresh product in 94% of patients with a median vein-to-vein time of seven days, eliminating the need for bridging therapy. T-cell subsets were assessed in the apheresis starting material and final CAR-T product. There was a higher proportion of early phenotypes of CD4+ and CD8+ CAR T cells (naive/stem cell memory and central memory T cells) in the final product compared with starting material, indicating an increase of those populations during the manufacturing process. This demonstrates the feasibility of Galapagos’ decentralized manufacturing platform to deliver a high-quality CAR T-cell product to patients.

The new data will be presented by Marie José Kersten, M.D., Professor of Hematology and Head of the Department of Hematology at the Amsterdam University Medical Center.

"We are committed to accelerating breakthrough innovations to extend the reach of CAR-T therapies to patients with rapidly progressing cancers," said Dr. Jeevan Shetty, M.D., Head of Clinical Development Oncology at Galapagos. "We are delighted to present promising new data for GLPG5101 at the EHA (Free EHA Whitepaper) congress. The high complete response rates, combined with low-grade CRS and ICANS, demonstrates the potential of GLPG5101 in addressing the critical needs of this patient population. The data also confirm the feasibility of our innovative decentralized T-cell manufacturing platform in delivering fresh, fit cells with a median vein-to-vein time of just seven days."

Key new data from the ongoing Phase 1/2 ATALANTA-1 study include:
As of the data cut-off date of December 20, 2023, 34 patients (17 in Phase 1 and 17 in Phase 2) received GLPG5101 with a median vein-to-vein time of seven days. Overall, safety results were available for 33 patients and efficacy results were available for 31 patients. The data are summarized below:

GLPG5101 showed an encouraging safety profile with most TEAEs1 of Grade 1 or 2; the majority of Grade ≥ 3 events were hematological. Two cases of CRS2 Grade 3 were observed in Phase 1 and one case of ICANS3 Grade 3 was observed in Phase 2.
In Phase 1, 14 of 16 efficacy-evaluable patients responded to treatment (objective response rate, ORR 87.5%), with 12 patients achieving a complete response (CR) (CR rate, CRR 75%). In Phase 2, 14 of 15 efficacy-evaluable patients responded to treatment (ORR 93.3%), and all responders achieved a complete response (CRR 93.3%).
High ORR and CRR were observed in the pooled Phase 1 and Phase 2 efficacy analysis set, split by indication:
In patients with DLBCL, 7 of 9 efficacy-evaluable patients responded to treatment (ORR 78%), with 5 patients achieving a complete response (CRR 56%).
In patients with FL or MZL, objective and complete responses were observed in 16 of 17 efficacy-evaluable patients (ORR and CRR 94%).
In patients with MCL, all 5 of 5 efficacy-evaluable patients responded to treatment (ORR and CRR 100%).
Durable responses were observed in the majority of responding patients:
71% of patients in Phase 1 had an ongoing response at data cut-off with median follow-up of 13.1 months.
100% of patients in Phase 2 had an ongoing response at data cut-off with median follow-up of 4.2 months.
Strong and consistent in vivo CAR-T expansion levels and products consisting of early phenotype T cells were observed in all doses tested.
Presentation details:

Abstract number/title Authors/Presenter Presentation date/time
Abstract #S243
Seven-Day Vein-to-Vein Point-of-Care Manufactured CD19 CAR T Cells (GLPG5101) in Relapsed/Refractory Non-Hodgkin Lymphoma: Results from the Phase 1/2 Atalanta-1 Trial Marie José Kersten, Kirsten Saevels, Sophie Servais, Evelyne Willems, Marte C. Liefaard, Stavros Milatos, Margot J. Pont, Claire Vennin, Eva Santermans, Anna D.D. Van Muyden, Maria T. Kuipers, Sébastien Anguille, Joost S.P. Vermaat Saturday, June, 15
12:15- 12:30 pm CET

​Session s422: Aggressive lymphoma – CAR-T cell therapy
Hall Dali 2

About the ATALANTA-1 study (EudraCT 2021-003272-13)
ATALANTA-1 is an ongoing Phase 1/2, open-label, multicenter study to evaluate the safety, efficacy and feasibility of decentralized manufactured GLPG5101, a CD19 CAR-T product candidate, in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL). GLPG5101 is a second generation anti-CD19/4-1BB CAR-T product candidate, administered as a single fixed intravenous dose. The primary objective of the Phase 1 part of the study is to evaluate the safety and preliminary efficacy to determine the recommended dose for the Phase 2 part of the study. Secondary objectives include assessment of efficacy and feasibility of near the point-of-care manufacturing of GLPG5101. The dose levels that were evaluated in Phase 1 are 50×106 (DL1), 110×106 (DL2) and 250×106 (DL3) CAR+ viable T cells. The primary objective of the Phase 2 part of the study is to evaluate the objective response rate (ORR), while the secondary objectives include complete response rate (CRR), duration of response, progression free survival, overall survival, safety, pharmacokinetic profile, and the feasibility of decentralized manufacturing. Each enrolled patient will be followed for 24 months.

About non-Hodgkin lymphoma
Non-Hodgkin lymphoma is a cancer originating from lymphocytes, a type of white blood cell which is part of the body’s immune system. Non-Hodgkin lymphoma can occur at any age although it is more common in adults over 50 years old. Initial symptoms usually are enlarged lymph nodes, fever, and weight loss. There are many different types of non-Hodgkin lymphoma. These types can be divided into aggressive (fast-growing) and indolent (slow growing) types, and they can be formed from either B lymphocytes (B cells) or in lesser extent from T lymphocytes (T cells) or Natural Killer cells (NK cells). B-cell lymphoma makes up about 85% of non-Hodgkin lymphomas diagnosed in the US. Prognosis and treatment of non-Hodgkin lymphoma depend on the stage and type of disease.

About Galapagos’ T-cell manufacturing platform
Galapagos’ decentralized, innovative T-cell manufacturing platform has the potential for the administration of fresh, fit cells within a median vein-to-vein time of seven days, greater physician control and improved patient experience. The platform consists of an end-to-end xCellit workflow management and monitoring software system, a decentralized, functionally closed, automated manufacturing platform for cell therapies (using Lonza’s Cocoon) and a proprietary quality control testing and release strategy.

On June 14, 2024 Immune-Onc Therapeutics, Inc. ("Immune-Onc"), a clinical-stage biopharmaceutical company advancing novel therapies in immunology and oncology by targeting myeloid cell inhibitory receptors, reported the company will present additional positive interim Phase 1b expansion cohort data for IO-202 in patients with chronic myelomonocytic leukemia (CMML) at the 2024 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting held virtually and in Madrid, Spain, June 13 – 16 (Press release, Immune-Onc Therapeutics, JUN 14, 2024, View Source [SID1234644351]).

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CMML is a rare hematologic malignancy with poor survival outcomes, incurable with conventional therapy, and has no effective standard of care. Currently, hypomethylating agents (HMA), including azacitidine (AZA), are the only FDA-approved treatment option for CMML with only a 7-17% complete remission (CR) rate.

Promising early-cycle responses, including a 53.8% (7 out of 13) CR rate (4 CR, 1 CR equivalent, and 2 CR bilineage), based on International Working Group 2023 response criteria, were observed in CMML patients treated with IO-202 in combination with AZA, with CRs lasting ten months and ongoing. The Phase 1b interim data continue to demonstrate that IO-202 is well tolerated.

"Chronic myelomonocytic leukemia remains a disease with poor prognosis and risk of progression into acute myeloid leukemia (AML), resulting in a critical need for innovative medicines," said IO-202 Phase 1b investigator Courtney DiNardo, M.D., MSCE, professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, Houston, TX. "We are encouraged by Phase 1b trial data showing early and sustained complete remissions among CMML patients, regardless of their prognosis or mutation status. This supports the potential of IO-202 in combination with azacitidine as a frontline therapy for CMML patients, and we are pleased to share these data with the medical community at EHA (Free EHA Whitepaper) this year."

"IO-202 has favorable tolerability, a well-understood mechanism of action, and a consistent efficacy response that supports further study as a treatment option in both AML and CMML patients," said Charlene Liao, Ph.D., chief executive officer of Immune-Onc. "We look forward to continued collaborations with our investigators and the FDA to plan and conduct our registrational study in frontline CMML patients."

Poster presentation details:

Abstract Number: P792 (here)
Title: Targeting LILRB4 (ILT3) Using IO-202 in Patients with Chronic Myelomonocytic Leukemia (CMML): Interim Efficacy, Safety, and Mechanism of Action Data from the Phase 1b Expansion Cohort
Presenter: Ahmed Aribi, M.D., assistant professor, Division of Leukemia, City of Hope in Duarte, CA
Session Title: Myelodysplastic Syndromes – Clinical
Session Date and Time: Friday, June 14, 6-7 p.m. CEST

ABOUT CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML)

CMML is a rare form of blood cancer, occurring in 4 of every 1,000,000 people in the United States each year,1 or about 1,100 annual cases.2 CMML is characterized by a high monocyte count (>1×109/L peripheral monocytes with monocytes ≥ 10% of white blood count) and dysplastic features in the bone marrow.1 Current FDA-approved therapies for CMML are all hypomethylating agents, including azacitidine, only achieving a 7%-17% complete response rate.1

ABOUT LILRB4 (also known as ILT3)

LILRB4, also known as ILT3, is an immune-modulatory transmembrane protein found on monocytes and monocyte-derived cells. LILRB4 is expressed on certain hematologic cancer cells, such as myelomonocytic leukemia blasts, and on certain pathogenic cells involved in autoimmunity and inflammatory processes.

ABOUT IO-202

IO-202 is a first-in-class IgG1 antibody with specific, high-affinity binding to LILRB4 and depletes LILRB4 positive cells via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. As such, IO-202 is a targeted therapy with broad potential in blood cancers and autoimmune and inflammatory diseases.

IO-202 has completed the dose escalation part of the first-in-human, multicenter, open-label Phase 1 study in the U.S., and the data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in 2023. This Phase 1 trial has advanced to the dose expansion stage to evaluate IO-202 in combination with azacitidine (NCT04372433) in patients with newly diagnosed chronic myelomonocytic leukemia (CMML) who have not received any hypomethylating agents (HMA).

The U.S. Food and Drug Administration granted IO-202 Fast Track Designations for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) and relapsed or refractory CMML, respectively. The FDA has also granted IO-202 Orphan Drug Designations for the treatment of AML and CMML, respectively.