ALK translocation

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.

P2, N=29, Recruiting, Sheba Medical Center

This study shows the wide clinical spectrum of abdominal IMTs and affirms the poor prognosis of EIMS, raising discussion about its status as IMT subtype. Furthermore, the newly detected alterations of the RTK/PI3K/AKT pathway expand the molecular landscape of IMTs and provide potential therapeutic targets.

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

P3, N=327, Recruiting, UNICANCER | Trial completion date: Sep 2024 --> Sep 2026 | Trial primary completion date: Mar 2024 --> Sep 2026

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2023 --> Apr 2024

P2, N=246, Active, not recruiting, UNICANCER | Trial completion date: Jan 2023 --> Jan 2024

No NTRK or ALK translocations or increased copy number/amplification were identified in all eight cases which had fluorescence in situ hybridisation and/or next generation sequencing for NTRK1-3 and ALK available for assessment. None of the cases expressed BRAF-V600E.Although our study is limited, our report is the first to document PanTRK expression in AFH in the absence of identifiable NTRK1-3 gene alterations.

It describes key genetic alterations and their clinical implications. It also proposes recommendations on cytogenetic methods for MTNKN diagnosis.

In comparisons with the inoculation of STAT3-KD cells reconstituted with wild-type STAT3, the inoculation of STAT3-KD cells reconstituted with the K685R mutant significantly enhanced tumorigenesis and hepatosplenomegaly in nude mice. Collectively, these results revealed for the first time that the acetylation of STAT3 at K685 attenuated NPM-ALK-induced oncogenesis.

P1, N=111, Recruiting, M.D. Anderson Cancer Center | Phase classification: P1b --> P1

P1/2, N=238, Recruiting, NeoImmuneTech | Phase classification: P1b/2a --> P1/2

P1b, N=44, Terminated, Pfizer | Active, not recruiting --> Terminated; Termination of further treatment on the study due to the availability of commercial supply or a rollover study (NCT05160922) that will allow active subjects to continue receiving treatment.

Median prior therapy lines was 3 (range 2-5); all pts previously received Crizotinib, two pts received also Alectinib and 1 Ceritinib as TKI treatment. Lorlatinib represents a safe and effective salvage therapy for ALK+ Lymphoma patients failing first line TKI treatment. The obtainment of CR at M1 seems to represent a pivotal prognostic factor. Lorlatinib also offers a promising bridging regimen to salvage ASCT especially for ALK+ BCL patients, with high response rates and no additional toxicities, .

Crizotinib and alectinib are first- and second-generation ALK TKIs, respectively, approved for the treatment of ALK-positive ALCL (ALK ALCL) and ALK NSCLC...Thus, to improve the clinical outcomes of ALK ALCL therapy, we investigated the synergistic efficacy of the combination of alectinib and the DNA-demethylating agent azacytidine, decitabine, or OR-2100 (an orally bioavailable decitabine derivative)...The combination of alectinib and OR-2100 markedly altered gene expression in ALCL cells, including that of genes implicated in apoptotic signaling, which possibly contributed to the synergistic anti-ALCL effects of this drug combination. Therefore, alectinib and OR-2100 combination therapy has the potential to improve the outcomes of patients with ALK ALCL.

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