Mavacamten (Camzyos®) is a myosin modulator which reduces the interactions between myosin and actin. These are overly activated in hypertrophic cardiomyopathy (HCM), a source of exaggerated ventricular contractility, energy loss, and impairment of diastolic function (relaxation). The Food and Drug Administration (FDA) and the European Medication Agency (EMA) approved mavacamten for the treatment of symptomatic obstructive HCM (NYHA class II or III) in adult patients in 2022 and 2023, respectively. The medication is not yet reimbursed in Belgium. As seen in its clinical development studies, mavacamten reduces the intraventricular gradient, improves functional capacity and reduces symptoms. It also seems to be an innovative alternative to septal reduction. Mavacamten is usually very well tolerated knowing that, through its mechanism of action, it causes a dose-dependent and reversible reduction in left ventricular ejection fraction, which must therefore be closely monitored. The good tolerance and the effectiveness of mavacamten seem to be maintained over time. Consequently, the recent European Society of Cardiology Updated Guidelines on cardiomyopathy (ESC 09/2023) already recommend mavacamten in the pharmacological management of obstructive HCM.

2023-09-01·Clinical cancer research : an official journal of the American Association for Cancer Research

Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma.

Article

作者: Szpurka, Anna M ; Junker, Niels ; Tap, William D ; Wagner, Andrew J ; Burgess, Melissa A ; Bahleda, Rastislav ; Chisamore, Michael ; Ceccarelli, Matteo ; Schöffski, Patrick ; Peterson, Patrick

PURPOSE:

The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment.

PATIENTS AND METHODS:

This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability.

RESULTS:

The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged < 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1-Q3) duration of therapy (olaratumab) was 6.0 (3.0-11.9; cohort 1), 14.4 (12.4-20.9; cohort 2), and 14.0 (6.0-21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1-positive tumors.

CONCLUSIONS:

Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.

2023-06-01·Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation

Reliability and validity of the simplified Chinese version of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator

Article

作者: Wang, Di ; Xiang, Junai ; Liu, Wenhui ; Wang, Qian ; Jiang, Kai ; Li, Jian ; Meng, Xiangmin ; Yan, Rong ; Shang, Meimei ; Xu, Juan

PURPOSE:

This study aimed to translate and culturally adapt the immune checkpoint modulator (ICM) subscale of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM) scale and to validate the FACT-ICM scale in Chinese cancer patients receiving immune checkpoint inhibitors (ICIs) treatment.

METHODS:

In total, 354 cancer patients treated with ICIs were included in our cross-sectional study including 2 phases. Firstly, the ICM subscale was translated and culturally adapted by standardized procedures. Then the FACT-ICM scale was validated, which included item analysis, content validity, floor and ceiling effects, internal consistency reliability, test-retest reliability, construct validity, convergent/divergent validity, and known-group validity.

RESULTS:

The content validity indexes at the item and scale level of the ICM subscale were greater than 0.8. No floor and ceiling effects were found. The Cronbach's α and McDonald's omega coefficients of the simplified Chinese version of the FACT-ICM scale were 0.935 and 0.936, and the intraclass correlation coefficient was 0.833 (95% confidence interval: 0.574-0.940). Confirmatory factor analysis confirmed the 5-subscale structure of the simplified Chinese version of the FACT-ICM scale (χ²/df = 2.144, RMSEA = 0.057, SRMR = 0.072, and CFI = 0.848). Convergent and divergent validity further supported the construct validity of the simplified Chinese version of the FACT-ICM scale. The known-group validity of the simplified Chinese version of the FACT-ICM scale was confirmed in patients with different physical statuses.

CONCLUSIONS:

The simplified Chinese version of the FACT-ICM scale is a valid and reliable instrument and can be used in clinical practice and research on cancer patients receiving ICIs treatment.

项与 Foxp3-#32 相关的新闻（医药）

2024-03-14

·PRNewswire

Mozart Therapeutics Presents Non-clinical Data on Lead Program, MTX-101 for Treatment of Autoimmune Diseases, at Society of Toxicology Annual Meeting 2024

Findings highlight tolerability and pharmacology of MTX-101 in humanized IL–15 transgenic mouse model SEATTLE, March 14, 2024 /PRNewswire/ -- Mozart Therapeutics, the leading developer of CD8 Treg modulators for the treatment of autoimmune and inflammatory diseases, today announce new non-clinical data for MTX-101. The data will be presented in a late-breaking poster presentation during the Society of Toxicology 63rd Annual Meeting, March 10‒14 in Salt Lake City, Utah. MTX-101 is an antibody-based bispecific autoimmune checkpoint inhibitor that selectively targets regulatory CD8 T cells. MTX-101 has limited cross-reactivity to its targets in animal models; therefore, a humanized IL-15 transgenic mouse model was utilized for non-clinical assessment of toxicity and pharmacology. Presentation highlights include: MTX-101 was well-tolerated following single and multiple doses in the humanized mouse model MTX-101 showed sustained binding to CD8 Treg and did not demonstrate off-target cell effects or cause an increase in detectable pro-inflammatory serum cytokines Serum concentrations of MTX-101 indicated high exposure and PK parameters consistent with antibodies Data derived from the humanized mouse model aligns with previous in vitro and in vivo findings for MTX-101 "We are pleased to present early data highlighting the non-clinical safety of MTX-101. Our data underline the utility of the humanized IL-15 transgenic mouse model to assess targeting human immune system receptors with limited cross-reactivity in conventional toxicology species," said Kristine Swiderek, Ph.D., Chief Scientific Officer at Mozart Therapeutics. "This model enables the non-clinical safety assessment and an understanding of the PK/PD relationship for MTX-101 to inform our clinical development strategy." The poster "Nonclinical Assessment of Toxicity and Pharmacology of MTX-101, a Novel KIRxCD8 Targeting Bispecific CD8 Treg Modulator, in Humanized Mouse" (Abstract #5081, Late-Breaking Session 3, March 14) can be accessed from the Mozart Therapeutics website. About MTX-101 MTX-101 is a bispecific CD8 Treg modulator targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore the intrinsic functions of regulatory CD8 T cells, acting early in the autoimmune disease process to suppress and eliminate pathogenic autoimmune cells, halt downstream inflammation, and prevent tissue destruction. About Mozart Therapeutics Mozart Therapeutics is focused on developing first-in-class disease-modifying therapies for autoimmune and inflammatory diseases, utilizing a novel approach to restoring immune system function by targeting the CD8 T regulatory network. The company is headquartered in Seattle, WA. For more information, visit and follow the company on LinkedIn @Mozart-tx. SOURCE Mozart Therapeutics

AACR会议

2023-11-13

·PRNewswire

Mozart Therapeutics Presents Preclinical Data for MTX-101, a Novel Bispecific CD8 Treg Modulator for Treatment of Autoimmune Diseases, at American College of Rheumatology Convergence 2023

SEATTLE, Nov. 13, 2023 /PRNewswire/ -- Mozart Therapeutics, a leading developer of CD8 Treg Modulators for the treatment of autoimmune and inflammatory diseases, presented preclinical pharmacology and tolerability data for MTX-101,a CD8 Treg modulator at the annual meeting of the American College of Rheumatology being held at the San Diego Convention Center in San Diego, CA. Presented findings demonstrate: CD8 Treg are present in rheumatological autoimmune diseases and show decreased expression of functional proteins and reduced responsiveness to stimulation relative to healthy donor CD8 Treg MTX-101 selectively binds CD8 Treg and enhances their killing of self-reactive CD4 T cells by blocking inhibitory KIR Enhanced MTX-101 mediated CD8 Treg function prevents self-reactive CD4 T cell expansion and inflammation, without unwanted immune cell activation or increase of pro-inflammatory cytokines In non-clinical safety studies, MTX-101 was well-tolerated at doses up to 50 mg/kg Data collectively support the therapeutic potential of MTX-101 for the treatment of autoimmunity including rheumatological diseases "These results are important because they show the therapeutic potential of MTX-101 and validate the ability MTX-101 to restore the functionality of CD8 Treg in autoimmune diseases and to reestablish immune balance," said Kristine Swiderek, PhD, Chief Scientific Officer at Mozart Therapeutics. The poster "Pre-Clinical Characterization of MTX-101, a Novel Bispecific CD8 Treg Modulator with the Potential to Restore CD8 Treg Functions in Patients with Rheumatological Autoimmune Diseases" (Abstract #0089) can be accessed from the Mozart Therapeutics website. About MTX-101 MTX-101 is a bispecific CD8 Treg Modulator targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore regulatory CD8 T cell function, acting early in the autoimmune disease process to halt downstream inflammation and prevent the perpetuation of tissue destruction. About Mozart Therapeutics Mozart Therapeutics is focused on developing first-in-class disease-modifying therapies for autoimmune and inflammatory diseases, utilizing a novel approach to restoring immune system function by targeting the CD8 T regulatory network. The company is headquartered in Seattle, WA. For more information visit and follow the company on LinkedIn @Mozart-tx. Media Contact: Julie Rathbun Rathbun Communications [email protected] 206-769-9219 SOURCE Mozart Therapeutics

AACR会议

2023-06-21

·PRNewswire

Mozart Therapeutics Presents Preclinical Data for MTX-101, a Novel CD8 Treg Network Modulator for Treatment of Autoimmune Disease, at FOCIS 2023 Annual Meeting

SEATTLE, June 21, 2023 /PRNewswire/ -- Mozart Therapeutics, a leading developer of CD8 Treg Modulators for the treatment of autoimmune and inflammatory disease, today announced the presentation of preclinical pharmacologic and tolerability data for MTX-101, a bispecific autoimmune checkpoint inhibitor, at the Annual Meeting of the Federation of Clinical Immunology Societies (FOCIS 2023). Presented findings include: MTX-101 is well-tolerated following a single dose in humanized mice MTX-101 selectively acts on CD8 Treg in blood and tissues and does not cause activation of other immune cells nor an increase of pro-inflammatory cytokines; MTX-101 possesses a favorable and antibody-like pharmacokinetic profile. The poster "Pre-clinical Pharmacologic and Tolerability Characterization of MTX-101, a Novel KIR x CD8 Targeting Bispecific CD8 Treg Modulator" (Abstract #1517124) can be accessed from the Mozart Therapeutics website. About MTX-101 MTX-101 is a bispecific CD8 Treg Modulator targeting inhibitory KIR and CD8 expressed on regulatory CD8 T cells. This autoimmune checkpoint inhibitor aims to restore regulatory CD8 T cell function, acting early in the autoimmune disease process to halt downstream inflammation and prevent further complication. The initial therapeutic focus for MTX-101 is gastro-intestinal autoimmune disorders. About Mozart Therapeutics Mozart Therapeutics is focused on developing disease-modifying therapies for autoimmune and inflammatory diseases that work by targeting a novel regulatory CD8 T regulatory cell network. The company is headquartered in Seattle, WA. For more information visit and follow the company on LinkedIn @Mozart-tx. SOURCE Mozart Therapeutics

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