ALK translocation

NSCLC in patients under 40years of age presents characteristics different from those in older patients. Various factors are implicated, one example being lower exposure to tobacco, and they can influence the distribution of histological subtypes and the frequency of mutations.

These findings provide novel insights into the molecular portrait of ALCL, that could help improve treatment strategies and the prognosis for ALCL patients.

On the order of 20% of NSCLCs bear activating mutations in EGFR and are treated with osimertinib and other kinase antagonists...Local treatment options to control thoracic disease include radiotherapy and surgery. In patients with extensive-stage disease, a platinum agent (cisplatin or carboplatin) combined with etoposide and an anti-PDL1 inhibitor (atezolizumab or durvalumab) for four cycles followed by anti-PDL1 maintenance therapy is the recommended first-line regimen.

P4, N=14, Pfizer, Inc

P1/2, N=215, Active, not recruiting, NeoImmuneTech | Trial completion date: Mar 2025 --> Dec 2024

P3, N=600, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2028 --> Sep 2027 | Trial primary completion date: Dec 2028 --> Sep 2027

P4, N=42, Not yet recruiting, Taihe hospital,Affiliated hospital of hubei university of medicine; Taihe hospital

P3, N=327, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | Trial completion date: Sep 2026 --> Jul 2027 | Trial primary completion date: Sep 2026 --> Jan 2026

Our patient experienced clinical benefit from first and second generation ALK inhibition in a chemotherapy refractory tumor. Tumor mutation profiling can identify mutations that may render tumors sensitive to targeted therapy with tyrosine kinase inhibitors.

P=N/A, N=80, Recruiting, University of Washington | N=40 --> 80

There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAF V600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

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

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

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

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.

Several agnostic drug-target matches have already been approved for clinical use, e.g., immune therapy for tumors with microsatellite instability (MSI) and/or high tumor mutation burden (TMB), NTRK1-3 and RET inhibitors for cancers carrying rearrangements in these kinases, and dabrafenib plus trametinib for BRAF V600E mutated malignancies. The existing format of data dissemination may not be optimal for agnostic cancer medicine, as conventional scientific journals are understandably biased towards the publication of positive findings and usually discourage the submission of case reports. Despite all the limitations and concerns, histology-independent drug-target matching is certainly feasible and, therefore, will be increasingly utilized in the future.

P1/2, N=413, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

Achieving long-term local control in pulmonary IMT can be challenging. Multimodality treatment is sometimes needed but the overall outlook remains good.

Three cases previously classified as PTCL CD30+CD15+ showed DUSP22/IRF4 rearrangements, favouring a diagnosis of ALCL, ALK-. Our results suggest that cases previously designated PTCL CD30+CD15+, likely fall within the spectrum of ALCL, ALK-; additionally, a subset of ALCL, ALK- with DUSP22/IRF4 rearrangement expresses CD15, consistent with previous reports and expands the immunophenotypic spectrum of this lymphoma subgroup.

Localized treatment with frequent monitoring may be sufficient in ALK-positive pcALCL until there is evidence of progression. Physicians should be aware of the overall spectrum of ALCL, including cutaneous limited disease, systemic disease, disease with NPM-ALK translocation, disease with ALK positivity and disease with skin recurrence.

P1/2, N=155, Active, not recruiting, Pfizer | Phase classification: P1b/2 --> P1/2

P1, N=40, Recruiting, NYU Langone Health | Phase classification: P1/2 --> P1

P1/2, N=215, Active, not recruiting, NeoImmuneTech | Trial completion date: Jun 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Nov 2024 | Recruiting --> Active, not recruiting

P=N/A, N=40, Recruiting, University of Washington | Suspended --> Recruiting

P3, N=600, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P3, N=304, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Initiation date: Feb 2024 --> Nov 2024

P2, N=27, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

P1/2, N=4, Terminated, Asha Nayak | N=40 --> 4 | Unknown status --> Terminated; The study was terminated due to poor accrual.

P2, N=246, Completed, UNICANCER | Active, not recruiting --> Completed

In our study, PD-L1 expression was significantly higher in squamous cell carcinomas and lower in adenocarcinomas, and was positively associated with MET and KRAS mutations, as well as the wild-type EGFR gene state. Nonetheless, additional studies are needed to further validate those associations and determine the clinical significance for immune checkpoint inhibitors of these factors.

P1/2, N=384, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2024 --> Dec 2024

P3, N=1538, Active, not recruiting, ImmunityBio, Inc. | Trial completion date: Jul 2024 --> Apr 2026 | Trial primary completion date: Jul 2024 --> Oct 2025

P1, N=65, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

This study proposes FDA-approved drugs with ALK inhibitory characteristics. Moreover, we identified pharmacophores sites that can be tested with other pharmacological libraries.

P1/2, N=110, Active, not recruiting, Triumvira Immunologics, Inc. | Recruiting --> Active, not recruiting

NGS reveals new ALK translocation partners. Both the malignant and reactive TCR repertoires in ALK+ ALCL patients are unique and do not consistently occur among different patients.

P2, N=34, Not yet recruiting, City of Hope Medical Center | Initiation date: Dec 2023 --> Apr 2024

P1/2, N=110, Recruiting, Sotio Biotech Inc. | Trial completion date: Jul 2039 --> Dec 2041 | Trial primary completion date: Jul 2024 --> Apr 2026

Blood samples collected post-targeted therapies revealed additional acquired mutations. The AlphaLiquid®100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

P1, N=242, Recruiting, ModernaTX, Inc. | Active, not recruiting --> Recruiting | N=108 --> 242

P2, N=43, Completed, Wake Forest University Health Sciences | Active, not recruiting --> Completed

Lung cancer displays differences by age at diagnosis which may have important implications for its clinical management.