PALETTE- Adaptive Platform Trial for Personnalisation of Sepsis Treatment in Children and Adults: a Multi-national, Treatable Traits-guided, Adaptive, Bayesian Basket Trial"

PALETTE is a perpetual adaptive platform to efficiently study sepsis interventions within 'treatable traits' in all-ages patients enabling prompt evaluation of pandemic treatments. Treatable traits, therapeutic targets identified by phenotypes or endotypes (defined by biological mechanism or by treatment response) through validated biomarkers (measurable characteristic reflecting normal or pathogenic processes, or treatment responses), may include multi-omics, cellular, immune, metabolic, endocrine features, or intelligent algorithms. PALETTE Bayesian adaptive design enables parallel investigations of multiple interventions for sepsis, and quick inclusion of pandemic pathogens. PALETTE's new conceptual model will respond to the challenges of standard approaches, i.e. series of sepsis trials, each investigating one or two interventions, expensive, time consuming, and inappropriate in pandemic context.

Start Date01 Apr 2026

Sponsor / Collaborator

Assistance Publique des Hôpitaux de Paris SA

NCT03787290 / SuspendedPhase 2

Examining Immune-Based Mechanisms of Action for Mild-Intensity Whole Body Hyperthermia (WBH) in the Treatment of Major Depressive Disorder

Overall, the objective of this pilot study is to utilize the IL-6 receptor antagonist tocilizumab to prospectively evaluate the role of IL-6 in the antidepressant and immunological effects of whole body hyperthermia (WBH). The study seeks to replicate findings thus far that WBH has an antidepressant effect by administering the intervention at a site not involved in studies to date. Moreover, the current proposal may help the investigators better understand the role of IL-6 in the pathogenesis and treatment of depression which might point to novel immune-based interventions for Major Depressive Disorder (MDD). Finally, the current proposal holds promise for better understanding of a novel treatment for MDD, which is among the leading causes of health-related disability in the world.

Start Date01 Dec 2025

Sponsor / Collaborator

The General Hospital Corp.

[+1]

NCT05846789 / RecruitingPhase 2IIT

A Phase II Trial of Carboplatin +/- Tocilizumab as Initial Therapy for Metastatic Triple Negative and ER-low Breast Cancers

This is a randomized Phase II study of carboplatin monotherapy vs. carboplatin combined with tocilizumab in in Black and non-Black patients with metastatic triple negative or ER low breast cancer.

Start Date01 Jul 2024

Sponsor / Collaborator

Indiana University

[+1]

100 Clinical Results associated with Tocilizumab

100 Translational Medicine associated with Tocilizumab

100 Patents (Medical) associated with Tocilizumab

6,819

Literatures (Medical) associated with Tocilizumab

01 Apr 2024·Journal of critical care

Serial electrical impedance tomography course in different treatment groups; The MaastrICCht cohort

Article

Author: Heines, Serge J H ; van Kuijk, Sander M J ; de Jongh, Sebastiaan ; van der Horst, Iwan C C ; Aydeniz, Eda ; van Bussel, Bas C T ; Schellens, Joep ; van Rosmalen, Frank ; Bergmans, Dennis C J J ; Tas, Jeanette

PURPOSE:

To describe the effect of dexamethasone and tocilizumab on regional lung mechanics over admission in all mechanically ventilated COVID-19 patients.

MATERIALS AND METHODS:

Dynamic compliance, alveolar overdistension and collapse were serially determined using electric impedance tomography (EIT). Patients were categorized into three groups; no anti-inflammatory therapy, dexamethasone therapy, dexamethasone + tocilizumab therapy. The EIT variables were (I) visualized using polynomial regression, (II) evaluated throughout admission using linear mixed-effects models, and (III) average respiratory variables were compared.

RESULTS:

Visual inspection of EIT variables showed a pattern of decreasing dynamic compliance. Overall, optimal set PEEP was lower in the dexamethasone group (-1.4 cmH₂O, -2.6; -0.2). Clinically applied PEEP was lower in the dexamethasone and dexamethasone + tocilizumab group (-1.5 cmH₂O, -2.6; -0.2; -2.2 cmH₂O, -5.1; 0.6). Dynamic compliance, alveolar overdistension, and alveolar collapse at optimal set PEEP did not significantly differ between the three groups.

CONCLUSION:

Optimal and clinically applied PEEP were lower in the dexamethasone and dexamethasone + tocilizumab groups. The results suggest that the potential beneficial effects of these therapies do not affect lung mechanics favorably. However, this study cannot fully rule out any beneficial effect of anti-inflammatory treatment on pulmonary function due to its observational nature.

01 Apr 2024·Seminars in arthritis and rheumatism

Baseline absolute monocyte count predicts lung function decline among patients with systemic sclerosis-associated interstitial lung disease: A post hoc analysis from the focuSSced trial

Article

Author: Khanna, Dinesh ; Huang, Suiyuan ; Denton, Christopher P ; Bernstein, Elana J

OBJECTIVE:

Interstitial lung disease (ILD) is the leading cause of death in adults with systemic sclerosis (SSc). The identification of biomarkers to predict progression of SSc-ILD is an important unmet need. The purpose of this study was to determine whether an elevated baseline absolute monocyte count (AMC) is associated with a decline in forced vital capacity (FVC) at 48 weeks among participants with SSc-ILD enrolled in the phase 3 focuSSced trial.

METHODS:

We performed a post-hoc analysis of the focuSSced trial, a multicenter, double-blind, randomized, placebo-controlled trial of adults with diffuse cutaneous SSc for ≤ 60 months. Participants received subcutaneous tocilizumab 162 mg or placebo weekly for 48 weeks. We examined the relationship between baseline AMC and FVC at 48 weeks using a General Linear Model adjusted for potential confounders.

RESULTS:

The 136 participants with SSc-ILD in focuSSced were included in this study. Among participants assigned to the placebo group, there was a statistically significant inverse association between baseline AMC and change in FVC from baseline at week 48 in both unadjusted (β coefficient -0.539, 95 % CI -1.032 to -0.047, p-value=0.032) and multivariable-adjusted (β coefficient -0.573, 95 % CI -1.086 to -0.060, p-value=0.029) models. Among participants with SSc-ILD assigned to the tocilizumab group, there was no statistically significant association between baseline AMC and change in FVC from baseline at week 48 in unadjusted or fully adjusted models.

CONCLUSION:

AMC may be a biomarker of disease progression in SSc-ILD, especially in those with early SSc with elevated circulating inflammatory markers. These results should be validated in other SSc-ILD cohorts.

01 Apr 2024·Journal of stomatology, oral and maxillofacial surgery

Study of various therapeutic strategies for the treatment of rapidly progressive periodontitis in experimental models

Article

Author: Isakov, Bakyt ; Isakov, Erkinbek ; Kalbaev, Abibilla ; Lobanchenko, Olga

Rapidly progressive periodontitis is a serious disease that leads to rapid degradation of periodontal tissues and can lead to tooth loss at a relatively young age. The purpose of this article is to study the effectiveness of various modern methods in the treatment of this disease on an experimental model. A model of the studied pathology was created - a rat with a destroyed circular ligament of the tooth and a ligature applied to the base of the teeth. 5 study groups were formed, where various treatment methods were used: the appointment of soft food, the combination of intramuscular administration of vitamin C and prednisolone, the combination of tocilizumab and dexamethasone, and the combination of photodynamic therapy and tocilizumab. Histological material was taken from experimental animals and evaluated. The best results were noted in the group of photodynamic therapy and tocilizumab, where there was a better histological picture with minimal signs of the inflammatory process and satisfactory indicators of clinical dynamics, this approach showed high efficiency in resolving inflammation in the area of the affected foci. The 2nd place was taken by the combination of tocilizumab and dexamethasone, in this group, accelerated positive dynamics were noted compared to other groups, but the results of histological examination were worse than in group 1. In 3rd place - the combination of ascorbic acid with dexamethasone and the appointment of soft food, where there were almost no differences in terms of histological results and clinical picture compared to the control group. The combination of tocilizumab with photodynamic therapy is promising in the treatment of patients with rapidly progressive periodontitis, but additional human studies are required to include this type of treatment in clinical guidelines.

261

News (Medical) associated with Tocilizumab

28 Jun 2024

·www.prnewswire.com

AbbVie Receives Positive CHMP Opinion for Epcoritamab (TEPKINLY®) for the Treatment of Adults with Relapsed/Refractory Follicular Lymphoma

If approved, epcoritamab (TEPKINLY®) will become the first and only bispecific antibody conditionally approved as a monotherapy in the European Union to treat both relapsed or refractory (R/R) follicular lymphoma (FL) and R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of prior therapy Positive CHMP opinion based on results from the Phase 1/2 EPCORE® NHL-1 study NORTH CHICAGO, Ill., June 28, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the conditional marketing authorization of epcoritamab (TEPKINLY®), the first and only T-cell engaging bispecific antibody administered subcutaneously (under the skin), as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more prior therapies. The European Commission decision on this indication for epcoritamab is anticipated later this year. "Patients with follicular lymphoma are likely to face disease recurrence and shorter durability of response with each subsequent line of treatment. This positive opinion recognizes the unmet need in the European Union for individuals with relapsed or refractory follicular lymphoma, following failure of other therapies," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. FL is typically an indolent (or slow-growing) form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases.1 In 2023, there were an estimated 13,000 cases of FL in Western Europe.2 FL is considered incurable with current standard of care therapies.3 The CHMP opinion is supported by overall and complete response data from the Phase 1/2 EPCORE® NHL-1 clinical trial in 128 patients with R/R FL treated with epcoritamab after two or more lines of prior therapy. The study included patients who were refractory to both anti-CD20 monoclonal antibody therapy and an alkylating agent, patients who were refractory to last prior treatment, and patients whose disease progressed within two years of first systemic therapy. The safety profile of epcoritamab in the pivotal cohort was similar to reports of epcoritamab monotherapy in the pivotal EPCORE NHL-1 diffuse large B-cell lymphoma (DLBCL) cohort.4 An additional cohort of 86 patients evaluated a 3-step-up dosing (SUD) schedule to reduce the incidence and severity of cytokine release syndrome (CRS), which is an associated adverse effect from immune-engaging cancer treatments. For the first full dose of this 3-step regimen, mandatory hospitalization was not required. In this cohort, the incidence of CRS was 49% (42 of 86 patients; 9% were grade 2). There were no grade 3 or higher CRS events. The data from this optimization cohort of the EPCORE NHL-1 study were recently published in the Lancet Haematology. "Each year, thousands of people in Europe are diagnosed with follicular lymphoma, and it's an upsetting reality that many of them will experience relapse and refractory disease," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "Patients deserve new treatment options, and this positive opinion is the first step to bringing epcoritamab to more patients who need it." Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication. About the Phase 1/2 EPCORE® NHL-1 Trial EPCORE® NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a dose escalation part; an expansion part; and an optimization part. The trial was designed to evaluate subcutaneous epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (B-NHL), including FL. In the expansion part, additional patients were enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed/refractory B-NHLs who have limited therapeutic options. The optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The primary endpoint of the expansion part was ORR as assessed by an IRC. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints. The primary endpoint of the optimization part was the rate of ≥ Grade 2 CRS events and all grade CRS events from first dose of epcoritamab through 7 days following administration of the second full dose of epcoritamab. Topline results of the study were shared in December 2023. More information can be found on (NCT03625037). About Follicular Lymphoma (FL) FL is typically an indolent (or slow-growing) form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30% of all cases.1 FL is considered incurable with current standard of care therapies.3 Patients often relapse and with each relapse, the remission and time to next treatment is shorter.5 Over time, transformation to DLBCL, an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25% of FL patients.6 About Epcoritamab Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.7 Epcoritamab (approved under the brand name EPKINLY® in the United States and TEPKINLY® in the European Union) has received regulatory approval in certain lymphoma indications in several countries. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets. Both Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy and in combination across lines of therapy in a range of hematologic malignancies. Please visit clinicaltrials.gov for more information. EU Indications and Important Safety Information about Tepkinly®▼ (epcoritamab) Indications Tepkinly (epcoritamab) as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. Important Safety Information Contraindications Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use Cytokine release syndrome (CRS) CRS, which may be life-threatening or fatal, occurred in patients receiving Tepkinly. The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia. Other signs and symptoms of CRS in more than two patients include chills, tachycardia, headache and dyspnoea. Most CRS events occurred in Cycle 1 and were associated with the first full dose of Tepkinly. Administer prophylactic corticosteroids to mitigate the risk of CRS. Patients should be monitored for signs and symptoms of CRS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS. At the first signs or symptoms of CRS, institute treatment of supportive care with tocilizumab and/or corticosteroids as appropriate. Patients should be counselled on the signs and symptoms associated with CRS and patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Management of CRS may require either temporary delay or discontinuation of Tepkinly based on the severity of CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) ICANS, including a fatal event, have occurred in patients receiving Tepkinly. ICANS may manifest as aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral oedema. The majority of cases of ICANS occurred within Cycle 1 of Tepkinly treatment, however some occurred with delayed onset. Patients should be monitored for signs and symptoms of ICANS following Tepkinly administration. Patients should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS. At the first signs or symptoms of ICANS treatment with corticosteroids and non-sedating-anti-seizure medicinal products should be instituted as appropriate. Patients should be counselled on the signs and symptoms of ICANS and that the onset of events may be delayed. Patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. Tepkinly should be delayed or discontinued as recommended. Serious infections Treatment with Tepkinly may lead to an increased risk of infections. Serious or fatal infections were observed in patients treated with Tepkinly in clinical studies. Administration of Tepkinly should be avoided in patients with clinically significant active systemic infections. As appropriate, prophylactic antimicrobials should be administered prior to and during treatment with Tepkinly. Patients should be monitored for signs and symptoms of infection, before and after Tepkinly administration, and treated appropriately. In the event of febrile neutropenia, patients should be evaluated for infection and managed with antibiotics, fluids and other supportive care, according to local guidelines. Tumour Lysis Syndrome (TLS) TLS has been reported in patients receiving Tepkinly. Patients at an increased risk for TLS are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs or symptoms of TLS, especially patients with high tumour burden or rapidly proliferative tumours, and patients with reduced renal function. Patients should be monitored for blood chemistries and abnormalities should be managed promptly. Tumour flare Tumour flare has been reported in patients treated with Tepkinly. Manifestations could include localized pain and swelling. Consistent with the mechanism of action of Tepkinly, tumour flare is likely due to the influx of T-cells into tumour sites following Tepkinly administration. There are no specific risk factors for tumour flare that have been identified; however, there is a heightened risk of compromise and morbidity due to mass effect secondary to tumour flare in patients with bulky tumours located in close proximity to airways and/or a vital organ. Patients treated with Tepkinly should be monitored and evaluated for tumour flare at critical anatomical sites. CD20-negative disease There are limited data available on patients with CD20-negative DLBCL treated with Tepkinly, and it is possible that patients with CD20-negative DLBCL may have less benefit compared to patients with CD20- positive DLBCL. The potential risks and benefits associated with treatment of patients with CD20- negative DLBCL with Tepkinly should be considered. Immunisation Live and/or live-attenuated vaccines should not be given during Tepkinly therapy. Studies have not been conducted in patients who received live vaccines. Fertility, pregnancy and lactation Tepkinly is not recommended during pregnancy and in women of childbearing potential not using contraception. Effects on ability to drive and use machines Tepkinly has minor influence on the ability to drive and use machines. Due to the potential for ICANS, patients should be advised to exercise caution while (or avoid if symptomatic) driving, cycling or using heavy or potentially dangerous machines. Undesirable effects Summary of the safety profile The most common adverse reactions (≥ 20%) were CRS, fatigue, neutropenia, injection site reactions, musculoskeletal pain, abdominal pain, pyrexia, nausea, and diarrhoea. Serious adverse reactions occurred in 52% of patients. The most frequent serious adverse reaction (≥ 10%) was cytokine release syndrome (31%). Seven patients (4.2%) experienced a fatal adverse reaction (pneumonia in 3 (1.8%) patients, viral infection in 3 (1.8%) patients, and ICANS in 1 (0.6%) patient). Adverse reactions that led to discontinuation occurred in 6.6% of patients. Discontinuation of Tepkinly due to pneumonia occurred in 6 (3.6%) patients, viral infection in 3 (1.8%) patients, and CRS, ICANS, or fatigue in 1 (0.6%) patient each. Dose delays due to adverse reactions occurred in 32% of patients. Adverse reactions leading to dose delays (≥ 3%) were viral infections (9.6%), CRS (7.2%), neutropenia (4.8%), pyrexia (3.0%), and thrombocytopenia (3.0%). This is not a complete summary of all safety information. See Tepkinly® full Summary of Product Characteristics (SmPC) at Globally, prescribing information varies; refer to the individual country product label for complete information. About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, and bi-specific and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. Today, our expansive oncology portfolio is comprised of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit us at . About AbbVie AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at . Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube. AbbVie Forward-Looking Statements Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. 1 Lymphoma Research Foundation official website. . Accessed February 2024. 2 Kanas G, Ge W, Quek RGW, et al. Leukemia & Lymphoma. 2022;63(1):54-63. 3 Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study. Haematologica. 2023;108(3):822-832. doi: 10.3324/haematol.2022.281421. 4 Linton Kim, Vitolo Umberto, Jurczak Wojciech, et al. Epcoritamab monotherapy in patients with relapsed or refractory follicular lymphoma (EPCORE NHL-1): a phase 2 cohort of a single-arm, multicentre study. Lancet Haematol. 2024. S2352-3026(24)00166-2. 5 Rivas-Delgado A, Magnano L, Moreno-Velázquez M, et al. Response duration and survival shorten after each relapse in patients with follicular lymphoma treated in the rituximab era. Br J Haematol. 2018;184(5):753-759. doi:10.1111/bjh.15708. 6 Al-Tourah AJ, Gill KK, Chhanabhai M, et al. Population-based analysis of incidence and outcome of transformed non-Hodgkin's lymphoma. J Clin Oncol. 2008 Nov 10;26(32):5165-9. doi: 10.1200/JCO.2008.16.0283. Epub 2008 Oct 6. PMID: 18838711. 7 Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625. SOURCE AbbVie

Clinical ResultDrug ApprovalImmunotherapyCell Therapy

26 Jun 2024

·www.biospace.com

Lyell Immunopharma Reports Dose-dependent Clinical Activity from Phase 1 Trial of LYL797, a ROR1-targeted CAR-T Cell Product Candidate Enhanced with its Proprietary Anti-exhaustion Technology

Dose-dependent antitumor clinical activity in ROR1+ relapsed/refractory triple-negative breast cancer; 40% objective response rate and 60% clinical benefit rate at the highest dose cleared to date (150 x 106 CAR T cells) First demonstration that CAR T cells enhanced with anti-exhaustion technology can both expand and infiltrate into solid tumors No significant safety signal related to LYL797 observed in patients without lung involvement; treatable pneumonitis observed in patients with lung metastatic disease; dose escalation continues in separate cohorts Expanding development into new tumor types including ROR1+ relapsed/refractory platinum-resistant ovarian cancer, endometrial cancer, multiple myeloma and chronic lymphocytic leukemia IND submission completed for LYL119, Lyell’s next generation ROR1-targeted CAR T cell product candidate Investor Webcast with David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute and a lead investigator in the Phase 1 clinical trial, scheduled for 8:30 am ET today SOUTH SAN FRANCISCO, Calif., June 26, 2024 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, today announced initial clinical and translational data from its Phase 1 trial of LYL797, its first-generation reprogrammed ROR1 CAR T‑cell product candidate enhanced with proprietary anti-exhaustion technology. The initial dataset consists primarily of patients with triple-negative breast cancer (TNBC) and demonstrated dose-dependent antitumor clinical activity and the ability of LYL797 CAR T cells to proliferate, infiltrate tumors and kill cancer cells in patients with relapsed/refractory disease. Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and clinical benefit rate (CBR) of 60% at the 150 x 106 CAR T cell dose level, with a CBR of 38% across all dose levels evaluable to date. Common treatment-related adverse events in patients without lung metastases included Grade 1 and 2 cytokine release syndrome (CRS) and headache, and the expected cytopenia from lymphodepletion. There were no reports of immune effector cell-associated neurotoxicity syndrome (ICANS) attributed to LYL797. Pneumonitis occurred in patients with lung metastases and dose escalation is continuing separately and more gradually in those patients. No dose-limiting toxicities have been reported in patients without lung involvement. All patients are now receiving prophylactic steroids prior to LYL797 treatment. “These are promising initial clinical findings demonstrating that LYL797 ROR-1-targeted CAR T cells had dose-dependent antitumor clinical activity and have the potential to deliver even more meaningful and durable benefit to patients as we continue to dose escalate,” said David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute, medical oncologist and a lead investigator in the LYL797 study. “Pneumonitis is a known complication of radiotherapy and several approved cancer therapies, including immune checkpoint blockade and several antibody-drug conjugate therapies. We have implemented a protocol using steroids, the standard of care for treatment of patients with pneumonitis, that I believe will enable us to successfully monitor and manage these events.” The LYL797 study includes a robust translational program from which Lyell reports the first demonstration that CAR T cells enhanced with anti-exhaustion technology expanded, persisted and infiltrated into solid tumors, in some cases with associated evidence of cancer cell killing. TIGIT, a marker of T cell exhaustion, was measured in samples collected on Day 11 post-infusion with only a low proportion of LYL797 CAR T cells demonstrated to be TIGIT-positive. RNAseq data also suggested a significant proportion maintained the targeted stem-like and effector memory cell phenotype. “We are encouraged to see clinical responses and a clear dose-dependent indication of antitumor clinical activity from treatment with LYL797 in patients with advanced triple-negative breast cancer,” said Lynn Seely, MD, President and Chief Executive Officer of Lyell. “Our translational data provide, to our knowledge, the first demonstration of persistent CAR T cell infiltration into solid tumors associated with evidence of cancer cell killing. This early validation of our anti-exhaustion technology gives us the conviction to expand our trial to include patients with ROR1+ ovarian or endometrial cancers, while continuing to enroll patients with triple-negative breast or non-small lung cancers, and also to initiate a new clinical trial for patients with multiple myeloma and chronic lymphocytic leukemia. This compelling early clinical data from LYL797 gives us a high degree of confidence to advance LYL119, our next generation ROR1-targeted product candidate with even more powerful anti-exhaustion technology. We have submitted an IND for LYL119 and expect to enter the clinic this year.” Initial LYL797 Phase 1 Clinical Trial Results This initial dataset of 20 treated patients includes 16 patients with TNBC and four patients with non-small cell lung cancer. All patients enrolled had relapsed/refractory metastatic disease and the mean lines of prior therapies for metastatic disease was six. Four dose levels, including two interim dose levels, have been explored to date: 50 x 106 cells, 100 x 106 cells, 150 x 106 cells and 300 x 106 cells. The efficacy evaluable subset includes 16 patients, and the safety evaluable subset includes 18 patients. The manufacturing success rate was 100%. Of the five patients with TNBC treated with LYL797 at the 150 x 106 cell dose level, the highest dose level cleared to date, two patients had confirmed partial responses to Day 90, resulting in an ORR of 40%. The CBR, defined as a best response of stable disease, partial response or complete response, was dose-dependent with 60% at the 150 x 106 cell dose level and 38% across all four dose levels evaluated. The most frequently reported related adverse events of any grade are CRS (61%), pneumonitis (22%) and headache (17%), as well as the expected cytopenia from lymphodepletion in all patients. The CRS was generally mild (Grade 1 or 2 only), characterized by fever, and treated with tocilizumab and steroids. There were no reports of immune effector cell-associated neurotoxicity syndrome (ICANS) attributed to LYL797. The most frequently reported Grade > 3 related adverse events were pneumonitis (17%) and hypoxia (11%), as well as the expected cytopenia from lymphodepletion in 78% of patients. One patient had Grade 5 respiratory failure on Day 41. The adverse event of Grade > 3 pneumonitis occurred only in patients with TNBC and lung metastases, resulting in the separation of dose escalation into two cohorts based upon lung involvement (lung primary, lung metastatic disease or pleural effusion). No dose-limiting toxicities occurred in patients without lung involvement. All patients are now receiving prophylactic therapy with dexamethasone to mitigate pneumonitis. Patients without lung involvement are currently under evaluation at the 300 x 106 cell dose level and patients with lung involvement are currently under evaluation at 75 x 106 cell dose level. Translational data are described on a subset of patients and include CAR T cell expansion in peripheral blood, phenotypic analysis of T cell exhaustion and stem-like markers and on-study tumor biopsies to assess for CAR T cell tumor infiltration. LYL797 CAR T-cell expansion was observed in peripheral blood samples at Day 60 in all patients assessed to date (n = 11) with peak expansion occurring between Days 8 and 11. Peak expansion was on average three-fold higher in patients receiving 150 x 106 cells compared to those receiving 50 x 106 cells. The exhaustion marker, TIGIT, was found only in a low proportion of LYL797 CAR T cells at Day 11 (n = 4) providing support for the role of c-Jun overexpression as an anti-exhaustion technology. A significant proportion of cells with stem-like and effector memory phenotypes were demonstrated at Days 11 and 22 following RNAseq transcriptomic analysis supporting the role of Epi-R to preserve a stem-like phenotype. Nine evaluable on-treatment tumor biopsies collected between Days 21 and 30 after LYL797 infusion were assessed. LYL797 CAR T cells were present in all solid-tumor biopsies, indicating that LYL797 CAR T cells enhanced with Lyell’s anti-exhaustion technology were able to infiltrate and persist in the solid tumor microenvironment. In addition, the tumor biopsies have features consistent with T cell-mediated tumor lysis, including T cell-rich inflammation with scattered tumor cells. Conference Call and Webcast Details Lyell’s management, together with David R. Spigel, MD, Chief Scientific Officer at the Sarah Cannon Research Institute and a lead investigator in the Phase 1 clinical trial, will host an investor conference call and Webcast beginning at 8:30 am ET today, to discuss the initial data from the LYL797 Phase 1 clinical trial. The Webcast can be accessed here. To join the live conference call, please register here to receive a dial-in number and unique PIN to access the call. It is recommended callers join ten minutes prior to the start of the event (although you may register and join at any time during the Webcast). A replay of the event and presentation materials will be archived on the Investor page of the Lyell Website following the end of the event. LYL797 Phase 1 Clinical Trial Design (NCT05274451) The Phase 1 clinical trial is designed as an open-label, dose-escalation and expansion trial in patients with relapsed/refractory TNBC who have failed at least two lines of therapy and NSCLC who have failed at least one line of therapy. The trial has been amended to also include patients with platinum-resistant ovarian cancer or endometrial cancer. All patients enrolled have tumor specimens positive for ROR1 protein expression by immunohistochemistry. More information on the Phase 1 trial can be found on clinicaltrials.gov here. About LYL797 LYL797 is a receptor tyrosine kinase-like orphan receptor 1 (ROR1) -targeted CAR T‑cell product candidate enhanced with Lyell’s anti-exhaustion genetic reprogramming technology (c-Jun) and epigenetic reprogramming technology (Epi-R). LYL797 overexpresses c-Jun to correct for an imbalance in the AP-1 family of transcription factors present in exhausted T cells. In preclinical studies, overexpression of c-Jun enables T cells to resist exhaustion, infiltrate solid tumors and maintain their functionality. LYL797 is manufactured utilizing Epi‑R, Lyell’s proprietary ex vivo manufacturing protocol that is designed to generate populations of stem-like T cells with reduced exhaustion and improved proliferation and antitumor activity. ROR1 is a fetal protein expressed during embryogenesis and is believed to be important in cell migration, polarity and survival. Significant subsets of patients with common cancers express ROR1 and it is generally associated with a poor prognosis. About Lyell Immunopharma, Inc. Lyell is a clinical-stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors. Lyell is currently enrolling a Phase 1 clinical trial evaluating a first-generation ROR1-targeted CAR T-cell therapy enhanced with anti-exhaustion technology in patients with relapsed/refractory triple-negative breast cancer, non-small cell lung cancer (NSCLC), ovarian cancer and endometrial cancer. A second Phase 1 clinical trial is ongoing to evaluate reprogrammed tumor infiltrating lymphocytes (TIL) in patients with advanced melanoma, NSCLC and colorectal cancer. An investigational new drug application has been submitted to the FDA for LYL119, a next-generation ROR1-targeted CAR T-cell product candidate with even more powerful anti-exhaustion technologies. The technologies powering Lyell’s product candidates are designed to address barriers that limit consistent and long-lasting responses to cell therapy for solid tumors: T-cell exhaustion and lack of durable stemness, which includes the ability to persist and self-renew to drive durable tumor cytotoxicity. Lyell is applying its proprietary ex vivo genetic and epigenetic reprogramming technologies to address these barriers to develop new medicines with improved durable clinical outcomes. Lyell is based in South San Francisco, California with facilities in Seattle and Bothell, Washington. To learn more, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements expressed or implied in this press release include, but are not limited to, statements regarding: the continued clinical progress of the LYL797 trials; the effectiveness of prophylactic steroids or other treatments to mitigate adverse events; the potential to deliver more meaningful and durable benefit to patients with dose escalation; Lyell’s plans to enroll patients with platinum-resistant ovarian cancer and endometrial cancer in the LYL797 trial; Lyell’s plans to submit an IND for LYL797 to initiate a new Phase 1 study evaluating LYL797 in patients with multiple myeloma or chronic lymphocytic leukemia and the timing thereof; Lyell’s development plans for LYL119 and the effectiveness of any technologies incorporated into LYL119; the ability of Lyell’s reprogramming technologies to infiltrate and persist in the solid tumor microenvironment; and other statements that are not historical fact. These statements are based on Lyell’s current plans, objectives, estimates, expectations and intentions, are not guarantees of future performance and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, but are not limited to, risks and uncertainties related to: macroeconomic conditions, including the effects of geopolitical instability and actual or perceived changes in interest rates and economic inflation; Lyell’s ability to submit planned INDs, obtain approval of submitted INDs, or initiate or progress clinical trials on the anticipated timelines, if at all; the potential for results from clinical trials to differ from nonclinical, early clinical, preliminary or expected results; Lyell’s limited experience as a company in enrolling and conducting clinical trials, and lack of experience in completing clinical trials; Lyell’s ability to manufacture and supply its product candidates for its clinical trials; the nonclinical profiles of Lyell’s product candidates or technology not translating in clinical trials; significant adverse events, toxicities or other undesirable side effects associated with Lyell’s product candidates; the significant uncertainty associated with Lyell’s product candidates ever receiving any regulatory approvals; Lyell’s ability to obtain, maintain or protect intellectual property rights related to its product candidates; implementation of Lyell’s strategic plans for its business and product candidates; the sufficiency of Lyell’s capital resources and need for additional capital to achieve its goals; and other risks, including those described under the heading “Risk Factors” in Lyell’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the Securities and Exchange Commission (SEC) on February 28, 2024, and the Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, filed with the SEC on May 6, 2024. Forward-looking statements contained in this press release are made as of this date, and Lyell undertakes no duty to update such information except as required under applicable law. Contact: Ellen Rose Senior Vice President, Communications and Investor Relations erose@lyell.com

Phase 1Cell TherapyClinical ResultImmunotherapyIND

25 Jun 2024

·www.globenewswire.com

TOFIDENCE™ (tocilizumab), a Biosimilar Referencing ROACTEMRA®, Approved in the European Union

TOFIDENCE™ complements existing portfolio of immunology biosimilars commercialized by Biogen June 24, 2024 -- Biogen Inc. (Nasdaq: BIIB) announced that the European Commission (EC) has granted approval for TOFIDENCETM, a biosimilar monoclonal antibody referencing ROACTEMRA®1. The intravenous formulation of TOFIDENCE has been granted marketing authorization by the EC for the treatment of moderate to severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis and COVID-19. “The approval of TOFIDENCE offers European patients with several inflammatory and immune-mediated inflammatory diseases access to an additional affordable biologic treatment option with comparable safety and efficacy to the approved reference product,” said Ian Henshaw, Global Head of Biosimilars at Biogen. “By adding TOFIDENCE to our growing biosimilars portfolio, we can provide greater choice to physicians and patients whilst offering the potential for significant cost-savings across healthcare systems in Europe.” The EC approval of TOFIDENCE is based on the totality of evidence comprising a comprehensive analytical, non-clinical and clinical data package. Extensive analytical characterization of the structural, physicochemical, and biological properties of TOFIDENCE was conducted and supports comparability with the reference biologic product. Additionally, a randomized double-blind, single-dose, three-arm, parallel group Phase 1 study compared the pharmacokinetics, safety and immunogenicity of TOFIDENCE with both the EU and US reference tocilizumab in healthy volunteers, while a randomized, double-blind, multi-dose, three-arm, parallel group Phase 3 study compared TOFIDENCE with tocilizumab to establish equivalent efficacy and comparable pharmacokinetic, safety and immunogenicity profiles, in subjects with rheumatoid arthritis inadequately controlled by methotrexate. The totality of evidence demonstrated TOFIDENCE is a biosimilar of the reference biologic. Biogen and Bio-Thera entered into a commercialization and licensing agreement for TOFIDENCE (BAT1806/BIIB800) in April 2021. Under the agreement, Biogen has exclusive regulatory, manufacturing, and commercial rights to TOFIDENCE in all countries excluding China (including Hong Kong, Macau and Taiwan). TOFIDENCE (tocilizumab), an interleukin-6 receptor antagonist, is a treatment developed as a biosimilar to the reference product ROACTEMRA. TOFIDENCE is indicated for the treatment of moderate to severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis and COVID-19. Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. References: RoActemra® is a registered trademark of Genentech, Inc. The content above comes from the network. if any infringement, please contact us to modify.

Drug ApprovalLicense out/inClinical Result

100 Deals associated with Tocilizumab

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KEGG	Wiki	ATC	Drug Bank
D02596	Tocilizumab	L04AC07	DB06273

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Interstitial lung disease due to systemic disease	US	Genentech, Inc.	04 Mar 2021
Still's Disease, Adult-Onset	JP	Chugai Pharmaceutical Co., Ltd.	22 May 2019
Takayasu Arteritis	JP	Chugai Pharmaceutical Co., Ltd.	25 Aug 2017
COVID-19	EU	Roche Registration GmbH	16 Jan 2009
COVID-19	IS	Roche Registration GmbH	16 Jan 2009
COVID-19	LI	Roche Registration GmbH	16 Jan 2009
COVID-19	NO	Roche Registration GmbH	16 Jan 2009
Cytokine Release Syndrome	EU	Roche Registration GmbH	16 Jan 2009
Cytokine Release Syndrome	IS	Roche Registration GmbH	16 Jan 2009
Cytokine Release Syndrome	LI	Roche Registration GmbH	16 Jan 2009
Cytokine Release Syndrome	NO	Roche Registration GmbH	16 Jan 2009
Giant Cell Arteritis	EU	Roche Registration GmbH	16 Jan 2009
Giant Cell Arteritis	IS	Roche Registration GmbH	16 Jan 2009
Giant Cell Arteritis	LI	Roche Registration GmbH	16 Jan 2009
Giant Cell Arteritis	NO	Roche Registration GmbH	16 Jan 2009
Juvenile Arthritis	EU	Roche Registration GmbH	16 Jan 2009
Juvenile Arthritis	IS	Roche Registration GmbH	16 Jan 2009
Juvenile Arthritis	LI	Roche Registration GmbH	16 Jan 2009
Juvenile Arthritis	NO	Roche Registration GmbH	16 Jan 2009
Oligoarticular Arthritis	EU	Roche Registration GmbH	16 Jan 2009

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoarthritis	Phase 3	FR	Hoffmann-La Roche, Inc.	20 Nov 2015
Pain	Phase 3	FR	Hoffmann-La Roche, Inc.	20 Nov 2015
Inflammation	Phase 3	DK	Hoffmann-La Roche, Inc.	28 May 2014
Inflammation	Phase 3	FI	Hoffmann-La Roche, Inc.	28 May 2014
Inflammation	Phase 3	NO	Hoffmann-La Roche, Inc.	28 May 2014
Inflammation	Phase 3	SE	Hoffmann-La Roche, Inc.	28 May 2014
Anemia	Phase 3	IT	Hoffmann-La Roche, Inc.	31 Oct 2009
Fatigue	Phase 3	IT	Hoffmann-La Roche, Inc.	31 Oct 2009
Edema	Phase 3	IT	Hoffmann-La Roche, Inc.	01 Oct 2009
Synovitis	Phase 3	IT	Hoffmann-La Roche, Inc.	01 Oct 2009

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ACTRIMS2024	Not Applicable	IL-6	-	Tocilizumab	nljimdywbd(jmfayvfmuo) = hljaiidund lvcahuvojy (ooofnexwuf ) View more	Positive	01 Mar 2024
				Rituximab	nljimdywbd(jmfayvfmuo) = ckcepejjod lvcahuvojy (ooofnexwuf ) View more
ChiCTR1900023710 (Literature) Manual	Phase 2	Nasopharyngeal Carcinoma	23	Toripalimab+capecitabine	thwupxyezy(ntxgpvmfsf) = zhvzoecbxi vceuqlstpy (qnbieiftsa, 78.1-99.9) Met View more	Positive	31 Jan 2024
NCT02385110 (CTgov)	Phase 2	Lymphohistiocytosis, Hemophagocytic \| Leukemia	18	Phone Call+etoposide+Dexamethasone+Methotrexate+Alemtuzumab (Group 1: Alemtuzumab + Etoposide + Dexamethasone)	gwlxwaepph(rccwueyetw) = zqvovlzsuj pmggoxtucv (oywpflkunb, tkwvniarvy - hdyupcmuav) View more	-	17 Jan 2024
				Phone Call+etoposide+tocilizumab+Dexamethasone+Methotrexate+Alemtuzumab (Group 2: Etoposide + Dexamethasone + Tocilizumab)	gwlxwaepph(rccwueyetw) = xlyhdcgkre pmggoxtucv (oywpflkunb, tcrvdxkxjs - xpqdcxhtva) View more
NCT04158440 (Neotorch, Literature) Manual	Phase 3	Non-Small Cell Lung Cancer	501	toripalimab	ajzppsceen(sykmbuunhv) = girrnhcwzw pqsbtfmefx (wllnmojcwe, 24.4 ~ NE) View more	Positive	16 Jan 2024
				Placebo	ajzppsceen(sykmbuunhv) = bdolckzewn pqsbtfmefx (wllnmojcwe, 10.6 ~ 21.9) View more
ASH2023	Not Applicable	-	31	Prophylactic tocilizumab	crswgnsufw(vfpcxzxnbu) = awmggffypl cxpdttzwin (lsbeuxjnjz ) View more	-	11 Dec 2023
NCT01664598 (CTgov)	Phase 3	Rheumatoid Arthritis	49	Tocilizumab	riepwiwbmg(sepdhcbxkp) = gtofhowjtg rbwnrkrqoq (aexingkfvl, tuermntidr - imsxyzhbui) View more	-	11 Dec 2023
ASH2023	Not Applicable	B-Cell Lymphoma	-	Mosunetuzumab	sjaczavnil(cbvlnmzhpk) = yncjcvibtx xhlqnkkmxi (gxerytkxkq )	-	09 Dec 2023
				Glofitamab	sjaczavnil(cbvlnmzhpk) = osjefhsvxu xhlqnkkmxi (gxerytkxkq )
ESMO_IO2023	Phase 2	Advanced Nasopharyngeal Carcinoma Adjuvant plasma Epstein-Barr virus (EBV) DNA	150	Neoadjuvant-adjuvant Toripalimab	irmwlxylsh(iykffisfcx) = brtgoeeehe rvstdxztcm (pmokinwand ) View more	Positive	07 Dec 2023
				Placebo	irmwlxylsh(iykffisfcx) = salpusxqcw rvstdxztcm (pmokinwand ) View more
ACR2023	Not Applicable	Giant Cell Arteritis interleukin-6	-	Tocilizumab	bpekumxgsf(bodashjucl) = qoeyurumnz lrmoosozac (dkyytkltlc )	Positive	14 Nov 2023
				No Tocilizumab	bpekumxgsf(bodashjucl) = gpslftcoqt lrmoosozac (dkyytkltlc )
REGATE (ACR2023)	Not Applicable	Rheumatoid Arthritis	1,496	Tocilizumab	plgqhvdpwy(knwfniswrf) = lhguxxeydq uvfztfaehk (ryjbdybips )	Positive	13 Nov 2023

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