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FoundationOne® CDx

This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC.

P2, N=1609, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2026 --> May 2027 | Trial primary completion date: Oct 2026 --> May 2027

Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

Extensive NGS analysis of PeM samples resulted in the identification of potentially effective targeted therapies for about one in four patients. Although these therapies are currently not available for patients with PeM, ongoing developments might result in new treatment options in the future.

P=N/A, N=400, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Trial primary completion date: Dec 2023 --> Jun 2024

A computational drug repurposing approach may assist in identifying novel repurposing events in cancer patients with no access to standard therapies. Further validation is needed to confirm a precision oncology approach using drug repurposing.

P2; Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

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.

The genomic signature was further validated using an independent dataset (n = 149), resulting in high-precision prognosis (AUC: 0.952; PPV = 0.974; NPV = 0.923). We anticipate that our genomic signatures and NCCN guidelines will improve recurrence predictions in CRC molecular stratification.

"Chugai Pharmaceutical Co., Ltd...announced that it has obtained approval from the Ministry of Health, Labour and Welfare (MHLW) on February 20, 2024, for FoundationOne CDx Cancer Genomic Profile to be used as a companion diagnostic to identify patients eligible for AstraZeneca K.K.’s AKT inhibitor, Truqap tablets (generic name: capivasertib), in combination with Faslodex (generic name: fulvestrant) for patients with advanced unresectable or recurrent HR-positive, HER2-negative breast cancer with specific PIK3CA, AKT1 or PTEN alterations, which was approved by the MHLW on March 26, 2024....The efficacy and safety of the combination therapy of capivasertib and fulvestrant in this specific form of breast cancer was evaluated in the global phase III CAPItello-291 study."

TSO500 and F1CDx showed robust analytical performance for TMB assessment with TSO500 showing stronger concordance of TMB with high PD-L1 expression. As the paradigm for the management of early-resected NSCLC continues to evolve, understanding TMB and the mutation landscape may help advance clinical outcomes for this subset of patients.

In EUS-TA, it is feasible to obtain the ideal sample for F1CDx using either the 19G 2-pass, 22G 4-pass, or 22G MOSE methods. Considering the number of punctures, procedure time, and incidence of adverse events, the use of 19G 2-pass or 22G MOSE is preferable.

According to the types of ICC by histopathological features, treatment target variants were detected significantly more frequently in sd-ICCs, with sd-ICC 8/9 (88.9%) and ld-ICC 0% (0/6), of which 3 patients were treated (Pemigatinib for 2cases, clinical trial for 1case). A: The success rate of CGP (tissue) examination was 100% (21/21) for resection specimens, 100% (9/9) for liver biopsy, and 3/7 (42.9%) for biopsy. B: The median TMB was 3 (IQR 1-4) and the median number of variants detected was 4 (IQR 2.5-6). The positive rate of therapeutic target variants per disease was 53.3% (8/15) for ICC, 25% (3/12) for BDC, 11.1% (1/9) for GBC, and 0% (0/1) for ampullary carcinoma.

P=N/A; Not yet recruiting --> Recruiting

We identified various factors associated with efficient and accurate CGP testing using relevant information obtained from real-world data, suggesting that thorough selection and preparation of tissue sections could optimize CGP and maximize useful information.

We found that the Japanese cohort with ductal adenocarcinoma has unique features such as high frequency of alterations in tumor suppressor gene such as TP53 and RB1 , and lack DDR pathway alterations, suggesting the existence of regional and racial differences in genomic profiles. Genomic analysis using next-generation sequencing is expected to be useful in elucidating the pathogenesis of ductal adenocarcinoma, and further accumulation of cases is considered important.

TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

HER2 gene expression was prognostic and predictive in CALGB/SWOG 80405. HER2 tumor expression may inform treatment selection for patients with low HER2 favoring bevacizumab- versus cetuximab-based therapies.

Moreover, this process is rapid, safe, inexpensive, scalable, and conserves patient surgical pathology material. NPE may constitute best practice with respect to enriching tumor cells from low-purity specimens for biomarker detection in molecular laboratories.

"Foundation Medicine, Inc...announced that research from its robust oncology diagnostics portfolio will be presented at the American Association for Cancer Research (AACR) Annual Meeting in San Diego, California April 5-10, 2024....In a retrospective study of 58 patients from the Genentech, a member of the Roche Group, MyPathway study (NCT02091141)...Results suggest ​serial early ctDNA monitoring ​is a valuable complementary tool for real-time treatment response monitoring to targeted therapy....Leveraging plasma collected serially from patients in Genentech’s Prospective Clinico-Genomic (PCG) study (NCT04180176), the FoundationOne Monitor assay was used to investigate ctDNA tumor fraction for monitoring treatment response."

Our study provides a comprehensive landscape of ancestry-specific patterns in KRAS and EGFR-altered non-Sq NSCLC. These findings can help better understand cancer disparities, aid in the development of new therapeutic strategies and inform more inclusive clinical trials and treatment decisions.

The incidence of PGV in NOP and PGPV in F1L and F1CDx were 4/321 (1.2%), 36/773 (4.7%), and 141/2145 (6.6%), respectively (NOP vs F1L vs F1CDx; p = 0.001 NOP vs F1L; p = 0.006, NOP vs F1CDx; p < 0.001, F1L vs F1CDx; p=0.190). The 4 PGVs detected by NOP were in the ATM, BRCA2, MSH6, and TP53 genes. Notably, two out of four patients were in their 30s while the other two were in their 70s.

In 52 cases, six cases (4 of SD cases and 2 of PR cases) was administered encorafenib-based chemotherapies based on BRAF gene mutation... Around 13% of gastrointestinal cancer patients with liver metastasis might have a druggable benefit by CGP testing. BRAF mutation might be promising target for patients with liver metastasis. ZNF217, SRC, ARFRP1, BARD1, FGF10 might be associated with metastatic process to liver in gastrointestinal cancer.

From 2019 to 2022, 1387 patients with STS were registered in C-CAT. The histological types included leiomyosarcoma in 357 patients, dedifferentiated liposarcoma in 178 patients, and undifferentiated pleomorphic sarcoma in 82 patients, and the others. The most commonly altered genes included TP53, CDKN2A, Rb1, and CDKN2B.

Responses to ceralasertib monotherapy were limited in ATM-altered tumors, despite reaching target plasma levels. Alternative pt selection and combination treatment strategies are being explored.

SKYSCRAPER-04 (NCT04300647) explored the clinical activity of Tiragolumab (T, anti-TIGIT) plus atezolizumab (A, anti-PD-L1) dual blockade (T+A) in patients (pts) with PD-L1+ cervical cancer. This exploratory analysis suggests that increased tumor immunity and mutation burden (TMB and PIK3CA-mut) correlates with improved ICB clinical outcomes. No biomarkers were clearly associated with tiragolumab outcome. These results are hypothesis generating and should be confirmed in an independent dataset.

The C-CAT database offers insights into the mutational landscape of various cancers and histological subtypes, especially those with poor prognosis, highlighting the unmet needs for drug development in these gynecologic cancers.

Chrovis-generated CGP reports did not require any changes in 82%s, suggesting that artificial intelligence reporting may lessen the burden of MTBs while contributing to its standardization. Recommendation for germline disclosure requires manual supervision, and improvements in clinical trial databases are required to correctly recommend genomically matched trials to patients.

Several small studies demonstrate objective but short-lived responses to SMO inhibitors such as vismodegib or sonidegib. We present the case of a 26-year-old patient with a recurrent MB, in which next-generation sequencing (FoundationOne CDx) revealed a mutation in PTCH1, allowing the patient to be treated with vismodegib in second line, resulting in a durable benefit lasting for 1 year. Using an in-house digital PCR probe, the PTCH1 mutation could be tracked in ctDNA during treatment with first-line chemotherapy and while on treatment with vismodegib, demonstrating a precise correlation with the radiological and clinical behavior of the disease.

"Chugai Pharmaceutical...announced that it has obtained approval from the Ministry of Health, Labour and Welfare (MHLW) on February 28, 2024, for FoundationOne^®CDx Cancer Genomic Profile to be used as a companion diagnostic for Eli Lilly Japan K.K.’s RET (rearranged during transfection) receptor tyrosine kinase inhibitor, Retevmo capsules (generic name: selpercatinib), for RET fusion-positive solid tumors."

P1; In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.

PTC was the most common histologic type of TC for which genetic profiling was performed in Japan, followed by ATC. Since the most common targetable mutation is the BRAF mutation, practical application of BRAF-targeted therapy can be an important treatment option for Japanese patients with TC.

We herein propose a TMB calculation method and a bioinformatics tool that is customizable to different NGS panels and sample types. We were not able to retrieve TMB values from FO algorithm using our own algorithm and NGS panel.

A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified.

Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.

Sarcoma panel Nanopore adaptive sampling can diagnose rare sarcoma types, such as FUS translocated Ewing's sarcoma, and aid in characterizing the molecular landscape. Furthermore, Nanopore analysis may facilitate blood-based tumor markers. Additional testing of a diverse sarcoma cohort is needed to evaluate the clinical utility of this approach.

Targetable genomic alterations were identified in all six patients' specimens analyzed using the F1CDx assay. GAS harbors various genomic alterations associated with sustained activation of signaling pathways or cell cycle regulation in addition to abnormalities in TP53, and precision medicine based on molecular profiling will be necessary to overcome GAS.

Pathologist-directed precision needle punch enrichment (aka NPE) directly from tissue blocks increases tumor purity, and consequently, yields a greater number of successful tests and complex biomarker determinations. Moreover, this process is quality-controllable, rapid, safe, inexpensive, scalable, and conserves patient surgical pathology material. NPE may constitute best practice with respect to effective and practical tumor enrichment from surgical specimens.

BMPR1A G298D mutation was exclusively identified in a subset of driverless neoplasms which were classified as granulosa cell tumors (3/27=11%). For BMPR1A-mutant tumors, the overall absence of any detectable known driver mutations supports our hypothesis that this alteration could be an alternative rare tumorigenic mechanism.

This study estimated TMB cut-off values for commercially available CGP panels. The results showed a good performance of all panels on clinical samples and the calculated cut-offs support better accuracy measures for TSO500. The validated cut-off values can drive clinical interpretation of TMB testing in clinical research and clinical practice.

Conclusion Tumor-based NGS frequently provides clinically significant information. It holds the potential to reveal specific therapeutic targets and contribute to clinical decision-making