ALK (Anaplastic lymphoma kinase)

P1, N=169, Active, not recruiting, AbbVie | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY. Compared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

P2, N=143, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=101 --> 143

P2, N=114, Active, not recruiting, Assistance Publique Hopitaux De Marseille | Recruiting --> Active, not recruiting | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Oct 2023 --> Oct 2024

The recognition of some reproducible histological features can help dermatopathologist in assessing these lesions and can provide clues to predict the underlying molecular driver. In this review, we will focus on clinical and morphological findings in molecular Spitz tumor subgroups.

No new safety signals were identified. Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

P2, N=58, Recruiting, Sun Yat-sen University | Not yet recruiting --> Recruiting | Trial primary completion date: Nov 2023 --> Jun 2024

P2, N=34, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

P2, N=21, Completed, Washington University School of Medicine | Active, not recruiting --> Completed

P2, N=54, Recruiting, Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Enrolling by invitation --> Recruiting | Trial completion date: Mar 2024 --> Dec 2027 | Trial primary completion date: Mar 2023 --> May 2027

P3, N=478, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

P2, N=137, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

In advanced NSCLC, ICI treatment was linked to an elevated risk of pneumonitis across all grades (1-5) as well as high-grade occurrences (3-5) compared to chemotherapy. Notably, individuals with squamous histology and high PD-L1 expression, along with those lacking a history of prior treatment, demonstrated a heightened susceptibility to developing immune-related pneumonitis of all grades (1-5) and high grades (3-5). These observations provide valuable insights for clinicians seeking to enhance the management of pulmonary toxicity associated with immunotherapy.

ALK-rearranged Spitz tumour confirmed with FISH analysis favour clinically benign behaviour despite atypical histomorphology or positive sentinel lymph node. Therefore, correlation of histomorphology, immunohistochemical stain and molecular study are important for the definitive diagnosis of this entity.

P4, N=50, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jul 2024 --> Jun 2025

No abstract available

Crizotinib, a first-generation ALK inhibitor, was approved in the USA in 2021 for pediatric patients and young adults with relapsed or refractory ALK-positive ALCL; however, its safety and efficacy have not been established in older adults...This podcast provides an overview of ALK-positive ALCL and IMT. We discuss the current treatment landscape, the role of ALK tyrosine kinase inhibitors, and areas of future research.

Analysis of single cell sequencing data demonstrated that DDR2 is restricted to mesenchymal-type tumor subpopulations and is enriched in Schwann Cell Precursor (SCP) subpopulations found in high-risk disease. These data define an unsuspected role for sitravatinib as a therapeutic agent in neuroblastoma and reveal a novel function for DDR2 as a driver of tumor growth and metastasis.

No abstract available

Both PNI and mGPS can be used as a reliable, inexpensive, and easily applicable prognostic index in the advanced lung cancer patients who had the targetable mutation and also received targeted therapy.

Some ADCs have already received accelerated FDA approval, and IHC was incorporated in many clinical trials evaluating ADC efficacy. As such, it is anticipated that ADCs may have a companion diagnostic IHC to guide patient selection.

P3, N=1152, Completed, Universität des Saarlandes | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Jan 2024 | Trial primary completion date: May 2025 --> Jan 2024

P1, N=18, Completed, Elpiscience Biopharma, Ltd. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Mar 2024

P2, N=4, Terminated, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | N=104 --> 4 | Recruiting --> Terminated; Sponsor R&D Strategy Adjustment

Furthermore, a patient with an ALK-rearranged tumor achieved a remarkable 3-year progression-free survival following crizotinib treatment. Overall, our findings deepen the understanding of the complex genomic landscape of PSCC, revealing actionable targets amenable to tailored treatment of this poorly characterized malignancy.

P1, N=50, Suspended, University of Washington | Recruiting --> Suspended

P1/2, N=46, Completed, Akeso | Active, not recruiting --> Completed | Trial completion date: Apr 2023 --> Dec 2023 | Trial primary completion date: Feb 2023 --> Dec 2023

The patient responded well with no evidence of residual or recurrent disease on follow-up imaging or surveillance esophagogastroduodenoscopy. Crizotinib was ultimately discontinued after 10 months of therapy, and the patient continues to undergo surveillance imaging for monitoring of disease burden.

Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

Our inhouse panel was associated with rapid TAT and faster initiation of systemic treatment. Approximately 30% of patients would not need tissue sent for NGS based on inhouse detection of a potentially actionable mutation.

It follows that the farnesyltransferase inhibitor (FTI) lonafarnib in addition to ALK TKIs act synergistically in neuroblastoma, inducing apoptosis in vitro. In particular, on combined treatment of neuroblastoma patient derived xenografts with an FTI and an ALK TKI complete regression of tumour growth is observed although tumours rapidly regrow on cessation of therapy. Overall, our data suggests that combined use of ALK TKIs and FTIs, constitutes a therapeutic approach to treat high risk neuroblastoma although prolonged therapy is likely required to prevent relapse.

This report suggests that if there are suspicious intraoperative manifestations, carrying out a biopsy simultaneously, using Hematoxylin and eosin (HE) staining, and a comprehensive Immunohistochemistry (IHC) panel are essential to diagnosing PC-ALCL to prevent misdiagnosis.

P4, N=50, Recruiting, Samsung Medical Center | Trial completion date: Aug 2023 --> Aug 2024

P1, N=102, Recruiting, Bayer | N=74 --> 102

P2, N=80, Active, not recruiting, Peking Union Medical College Hospital | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2027

P2, N=12, Active, not recruiting, Oncology Institute of Southern Switzerland | Recruiting --> Active, not recruiting | N=20 --> 12 | Trial completion date: Dec 2022 --> Dec 2024

P1/2, N=12, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

P3; With ∼5 years of follow-up, pembrolizumab plus chemotherapy provided clinically meaningful and durable improvements in survival outcomes versus chemotherapy alone in patients with previously untreated metastatic NSCLC with PD-L1 TPS <1%. These results continue to support pembrolizumab plus chemotherapy as a standard of care in this patient population.

We discuss the role of NGS as well as its potential benefit in patients with unresectable, ALK-negative metastatic disease. Considering this case and previous literature, we support the use of NGS for patients requiring systemic treatment.

The NGS testing revealed EML4::ALK fusion in three, STRN::ALK fusion in two, and ITSN2::ALK fusion in one. In conclusion, although ALK-rearranged PTCs have been associated with neutral gene expression profile from a BRAF-RAS scoring perspective, the "RAS-like" nuclear features were more commonly identified in this series, resulting in frequent indeterminate diagnosis of preoperative FNA.

The different imaging manifestations of mucinous adenocarcinoma are possibly due to the different amounts or viscosity of mucus produced, and the mechanisms of its formation may include (1) tumour cells in different shapes have different abilities to produce mucus; (2) tumours in different stages produce different amounts or viscosity of mucus; and (3) the TTF-1 and ALK genes affect the production of mucus.

Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.