TEST:

UW-Oncoplex™

P1, N=18, Active, not recruiting, University of Washington | Trial completion date: Mar 2026 --> Sep 2026

P1, N=18, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting

This report provides the first documented instances of NT in gynecological cancers, indicating that it may be a more widespread resistance mechanism than previously recognized. Routine re-biopsy and early integration of advanced molecular diagnostics into clinical practice will identify NT and provide insights into pathogenesis and eventual therapeutic options.

P1; Trial primary completion date: Sep 2024 --> Dec 2025

After left lower lobectomy, she subsequently developed bilateral pulmonary metastases and began treatment with her first EGFR tyrosine kinase inhibitor in 2003 with gefitinib...In the interim, she was treated with osimertinib from 2016 to 2021 until she developed progression in bilateral lung nodules...Recently her treatment was switched to afatinib, and she quickly obtained clinical improvement...Second, amivantamab is a reasonable treatment option for patients with an EGFR-KDD. Lastly, EGFR-targeted resistance mechanisms can evolve over time and space, and biopsies at the time of resistance can help inform treatment recommendations.

Clinically relevant genomic alterations are detectable using CSF-derived cfDNA across a range of pediatric brain tumors. Next-generation sequencing platforms are capable of producing a high yield of DNA alterations with 100% concordance rate with tissue analysis.

Inflammatory infiltrate is a promising prospectively tested predictive biomarker in pre-treated mCRPC. Although NIVO 1 mg/kg + IPI 3 mg/kg had more toxicities than NIVO 3 mg/kg + IPI 1 mg/kg, the efficacy results were consistently better. This dose schedule and biomarker should now be tested in a phase 3 clinical trial.

Despite this, only a subset of these patients underwent the indicated confirmatory sequencing. Further work is needed to identify barriers and facilitators to this testing, including the role of genetic counseling and consideration of upfront paired somatic-germline testing.

CSF liquid biopsy has potential as a minimally invasive method of disease detection for measuring treatment response and longitudinal disease surveillance. lpWGS on CSF-derived cfDNA can identify tumor-derived sCNVs even when CSF cytology is negative for malignant cells. lpWGS can reveal sCNVs that are clinically actionable without need for a tissue biopsy.

P2; N=30 --> 2 | Trial completion date: May 2025 --> Oct 2023 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Oct 2023; Withdrawal of funding

Subsequent evaluation of the patient's recurrence using a DNA-based targeted NGS panel at the University of Washington (UW OncoPlex) detected a ZFTA::NCOA2 fusion, prompting methylation reanalysis (NIH) using the recently released v12b6 DKFZ classifier, which matched to "Supratentorial Ependymoma, ZFTA fusion-positive". Conclusions While this case is unusual in the lack of traditional ependymal morphology, the morphologic findings are consistent with the underlying ZFTA::NCOA2 fusion.

These cases highlight the challenges in identifying MLH1-deficient prostate cancers using standard MSI testing and commercial sequencing panels, and support the utility of immunohistochemical assays and LMR- or sequencing-based MSI testing for detection of MMRd prostate cancers.