ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)

Patients completing two-years of pembrolizumab for NSCLC in an Australian cohort had high rates of KRAS mutation and PD-L1 expression; a proportion had brain metastases and treated oligoprogression. Progression post pembrolizumab was higher in PD-L1 TPS < 1% and in those without complete response.

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

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 abstract available

The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300 μs) were significantly increased compared to the short pulse duration-treated groups (100 μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

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.

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

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.

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.

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

Further research on next-generation TKIs regarding the localization of ROS1 and its fusion partners, binding sites for targeted drugs, and coadministration with other drugs is required. The correlation between TKIs and chemotherapy or immunotherapy in clinical practice requires further study.

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.

Moreover, so was the case with the concomitant expression of NTRK fusions and EGFR mutations. We present a case report of a patient with concomitant EGFR mutation and NTRK1 fusion.

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.

P3, N=740, Recruiting, Daiichi Sankyo | Trial completion date: Jun 2026 --> Apr 2028 | Trial primary completion date: Jun 2026 --> Feb 2028

P2, N=27, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025

Finally, we show that mutation phasing can be resolved to single strands across the entire genome of liver tumors from F1 mice. This strategy can be broadly used to distinguish the contributions of overlapping cancer relevant mutational processes.

Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation...Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1...Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.

A 4-fold increased prevalence of cancer was observed in men with genetic infertility compared to the general male population (8% vs. 2%; p = 4.4 × 10-3). Expanding genetic testing in andrology will contribute to the multidisciplinary management of SPGF.

Collectively, this study enhanced our understanding of NENA NSLA by elucidating the proteogenomic landscape and proposed saracatinib as a potential treatment for this patient population that lacks effective targeted therapies. The proteogenomic landscape in never-smoker lung cancer without known driver mutations reveals prognostic proteins and enhanced estrogen signaling that can be targeted as a potential therapeutic strategy to improve patient outcomes.

P2, N=117, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Sep 2024 | Trial primary completion date: Jun 2024 --> Sep 2024

P2, N=88, Not yet recruiting, SWOG Cancer Research Network | Initiation date: Feb 2024 --> May 2024

Therefore, to target NSCLC effectively precision nanomedicine has been adopted in recent times. Here, we present different nanoparticles that are used as precision nanomedicine and their effectiveness against NSCLC disease.

No abstract available

Biomarkers ATLAS (https://biomarkersatlas.com/) represents a unique, easily managing, and reliable diagnostic tool aiming to integrate clinical records with molecular alterations of NSCLC patients in the real-word Italian scenario.

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: May 2026 --> Dec 2024

P3, N=886, Completed, Pfizer | Active, not recruiting --> Completed

Advances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.

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

P2, N=137, Active, not recruiting, Daiichi Sankyo | Trial completion date: May 2024 --> May 2026

P1, N=53, Active, not recruiting, Pfizer | N=36 --> 53

P2, N=277, Active, not recruiting, Daiichi Sankyo | N=420 --> 277

Among patients who exhibited resistance to crizotinib, follow-up treatment of entrectinib and lorlatinib showed remarkable survival benefits. Newer-generation ALK/ROS1-targeted drugs showed efficacy in a cohort of crizotinib resistant ROS1 + patients. These results, when validated, could assist efficiently accruing ROS1 + patients.

There are three currently active sub-studies and one soon to be activated sub-study studying amivantamab-vmjw in MET amplification positive NSCLC (S1900J). Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC...One hundred seventy (7%) were submitted with the classification of "Other". The most common reasons included: no sub studies available, patient chose hospice, and patient transferred to different hospital.

There have been two treatment-related deaths, one due to cardiac arrest and one due to pneumonitis. Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities.

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

P1/2, N=381, Recruiting, Hutchmed | Trial completion date: Sep 2023 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Dec 2025

In this podcast, we discuss the importance of biomarker testing in advanced NSCLC and explore topics such as testing methodologies, effect of biomarker testing on patient outcomes, emerging technologies, and strategies for improving testing rates in the United States. Supplementary file1 (MP4 121301 KB).

P2, N=4, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Feb 2025

P2, N=6, Terminated, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Dec 2023 | Active, not recruiting --> Terminated; Study was terminated due to slow accrual.