Delving into the Latest Updates on CTLA-4-XTEN with Synapse

Overview

Basic Info

Drug Type

Fusion protein

Synonyms

cytotoxic T-lymphocyte protein 4 modulator (Amunix), CTLA-4-XTEN

Target

CTLA4

Mechanism

CTLA4 modulators(Cytotoxic T-Lymphocyte-Associated Antigen 4 modulators)

Therapeutic Areas

Immune System DiseasesSkin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Graft RejectionRheumatoid Arthritis

Originator Organization

Amunix, Inc.

Active Organization-

Inactive Organization

Amunix, Inc.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Treatment with immune checkpoint inhibitors is effective in various cancers, but may be associated with immune-mediated side effects in other organs. Among the more common ones is gastrointestinal tract involvement, especially colitis. In most patients, colitis is mild or responds to corticosteroid treatment. A smaller proportion of patients, more often those treated with cytotoxic T lymphocyte antigen-4 inhibitors, may have a more severe course of colitis, even life-threatening complications. In these patients, prompt action, timely diagnosis with endoscopic evaluation and early treatment with high-dose corticosteroids and, if ineffective, rescue therapy with biologic agents such as infliximab and vedolizumab are needed. We present three cases from our clinical practice, data on incidence and clinical presentation, current recommendations regarding diagnostic approach and treatment of immune checkpoint inhibitors induced colitis.

01 May 2024·AACE clinical case reports

Severe Hyponatremia Triggered by Immune Checkpoint Inhibitor Therapy in a Patient With Mulvihill-Smith Syndrome

Author: Tavdy, Tammy ; Mathias, Priyanka ; Lee, Hanna J. ; Samavedam, Janaki Manasa

Background/Objective:

Immune checkpoint inhibitors (ICI), including Programmed Cell Death 1, Programmed Cell Death Ligand 1, and Cytotoxic T-lymphocyte Associated Antigen 4 inhibitors, upregulate T-cell responses against tumor cells and are becoming a cornerstone in the treatment of various advanced solid and hematological cancers. Mulvihill-Smith Syndrome (MSS) is a rare genetic syndrome that has been associated with metabolic abnormalities and early-onset tumors, including malignancies. We report the first known case of ICI-induced hyponatremia attributable to syndrome of inappropriate antidiuretic hormone ADH release (SIADH) in a patient with MSS.

Case Report:

A 23-year-old female patient with MSS and hepatocellular carcinoma presented with recurrent hyponatremia. Assessment of fluid status and electrolytes revealed a euvolemic, hypotonic process consistent with SIADH shortly after initiating adjuvant therapy with atezolizumab, a Programmed Cell Death Ligand 1 inhibitor.

Discussion:

Endocrine etiologies for euvolemic hypotonic hyponatremia, including adrenal insufficiency and hypothyroidism, were excluded. The diagnosis of SIADH was confirmed based on electrolyte and osmolality studies. Sodium levels normalized with fluid restriction. Given the onset of hyponatremia 30 days after atezolizumab initiation, we posit that atezolizumab triggered severe hyponatremia due to SIADH.

Conclusion:

With the expanding utilization of ICIs, including in patients predisposed to malignancies such as MSS, vigilant monitoring for ICI-mediated electrolyte imbalances is crucial. Monitoring for hyponatremia and SIADH in the setting of ICI therapy is recommended.

01 Feb 2024·Translational andrology and urology

A narrative review of management of muscle-invasive bladder cancer perioperative period: will continuous and combined treatment be the new trend?

Review

Author: Gao, Mingchao ; Ran, Shengming ; Lan, Tianhang ; Li, Wenjie ; He, Wang

Background and Objective:

With the emergence of immunotherapy and targeted therapies, there are more options for the perioperative period management of muscle-invasive bladder cancer (MIBC), and various types of clinical studies are emerging, leading to the need to explore ways to choose the optimal treatment modality. This review aims to synthesize past and present treatment modalities and to explore future trends in the perioperative period cares of MIBC for the benefit of clinical practitioners.

Methods:

A non-systematic, literature search was conducted between March 5, 2023 and November 30, 2023 on PubMed using "perioperative period", "MIBC", "chemotherapy", "radiotherapy", "immunotherapy", "targeted treatment" and "combination" as keywords, along with a search for ongoing clinical studies that were related to the perioperative period of MIBC on classic.clinicaltrials.gov, some latest conference abstracts were also included as references.

Key Content and Findings:

The trend towards benefit from adjuvant chemotherapy in perioperative chemotherapy is gradually being recognized. Neoadjuvant immunotherapy, including single-agent immunization, like programmed cell death protein 1 (PD-1) inhibitors, programmed cell death 1 ligand 1 (PD-L1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, and double-immunization, has been confirmed by several clinical studies to be beneficial to clinical remission rates, and the combination regimen is superior to single-agent therapy. Targeted therapies such as antibody-drug conjugate (ADC) are entering MIBC perioperative studies. Multiple sequential and combination clinical studies are gradually disclosing preliminary data on efficacy and safety.

Conclusions:

Immunotherapy would become an essential perioperative treatment for MIBC, and continuous and integrated perioperative management may become the MIBC treatment mode of the future. ADC medicines will also be a hot research focus in the coming years.

100 Deals associated with CTLA-4-XTEN

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