TEST:

FoundationOne® Liquid CDx

P1/2; Phase classification: P2 --> P1/2

The potential association of positive LB with earlier relapse requires further investigation in larger cohorts with a longer follow-up. Results will be updated by the time of meeting.

It seems additional supportive information may be acquired through well-established ctDNA liquid biopsy test among this population. Role of ctDNA liquid biopsy test for precision tumor marker should be investigated for future study.

Liquid biopsy NGS emerges as a viable and valuable strategy for guiding personalized therapy. Given restricted accessibility to new drugs or clinical trials in Mexico, the use of blood-based CGP may enhance the identification of druggable alterations, thereby increasing the likelihood of accessing targeted drugs or enrolling in clinical trials.

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.

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.

TALA + ENZA improved outcomes compared with PBO + ENZA in patients with muts in specific non-HRR genes (regardless of HRR gene muts). TMPRSS2-ERG and RB1 emerged as candidate predictive biomarkers for differential efficacy favoring TALA + ENZA vs PBO + ENZA. PARP inhibitors may induce a synthetically lethal interaction with TMPRSS2-ERG-mediated inhibition of non-homologous end joining and help overcome RB1-mediated ENZA resistance.

Our exploratory analysis identified candidate gene expression signatures, including AR pathway elements, potentially associated with differential benefit from TALA + ENZA, reinforcing the potential for exploitable crosstalk between AR and DNA repair pathways. Though validation is necessary, a predictive multiomic signature for benefit from TALA + ENZA regardless of HRR alteration status was identified that included alterations in genes previously implicated in prognosis and expression of multiple AR target transcripts. Strikingly, it did not include any of the 12 HRR genes used in prospective stratification for TP-2, reinforcing the potential benefit for TALA + ENZA beyond HRR-deficient tumors.

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.

In patients without known driver oncogenes, mutations associated with approved therapeutic implications were detected in 12.0%. The detection of gene rearrangements using liquid biopsy may be limited compared with genetic mutations.

This is the first prospective analysis confirming that TF is a significant predictive marker of treatment efficacy in patients referred for early phase studies. Our findings suggest that TF could be a valuable tool in decision-making for phase I trial participation. Additionally, this research lays the groundwork for future exploration of TF in risk stratification of cancer patients in various clinical contexts.

This study demonstrates the feasibility of liquid biopsy in HNSCC and rare head and neck tumors, providing valuable therapeutic and prognostic insights. The findings underscore the potential of liquid biopsy as a valuable tool in clinical decision-making for head and neck cancer patients.

These data demonstrate that LBx can detect relevant genomic alterations across HNs, including at low clonal fractions, suggesting a potential clinical utility for identifying residual or emerging therapy-resistant clones that may be undetectable in site-specific tissue biopsies.

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.

Conclusions Importantly, our study highlights the potential of ctDNA in detecting clinically actionable mutations when tumour biopsies are unavailable. Conversely, ctDNA alone is not adequate in reporting TMB.

Guidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.

NGS ctDNA analysis in comprehensive genetic testing improves actionable mutation identification, vital for treating Asian NSCLC cases with high actionable mutation rates. Lower stages correlated with undetected blood-based NGS ctDNA assay results.

Of 230 patients, 21 were administered medication following multi-CGP testing data, especially frequent in biliary tumor patients. Multi-CGP testing might be particularly beneficial to patients with biliary tumors in Japan.

"AnHeart Therapeutics...and Foundation Medicine, Inc., today announced the companies have entered a strategic collaboration for the development and regulatory approval of Foundation Medicine’s tissue-based and liquid-based comprehensive genomic profiling tests, FoundationOne^®CDx and FoundationOne^®Liquid CDx, as companion diagnostics for AnHeart’s investigational next-generation ROS1 inhibitor, taletrectinib, in the United States....Taletrectinib is a potential best-in-class ROS1 inhibitor being evaluated for the treatment of patients with advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC), an underserved group of lung cancer patients in need of new options."

In this initial cohort study, ctDNA TF shows prognostic significance in mRCC with potential to inform expected longevity of patients. Liquid biopsy detects alterations characteristic of mRCC genomics, supporting its utility to identify drivers and potential targetable alterations. Risk stratification based entirely upon algorithmic determination independent of human interpretation has the potential to improve risk stratification in mRCC and improve treatment decisions.

BRCA2, ATM and CDK12 were the most prevalent single gene mutations and clinical benefit was observed with O + A. Other single gene mutations were rare, limiting interpretation. The greatest treatment benefit was observed in pts with BRCA mutations. Clinical trial information: NCT03732820.NR, not reached; BRIP1, RAD51B, RAD51D n=1; CHEK1, RAD51C n=0.

Clinical Trial Registration Number: NCT03395197 Sponsored by Pfizer Background: TALAPRO-2 demonstrated statistically significant improvement in radiographic PFS with 1L talazoparib (TALA) + enzalutamide (ENZA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without HRR gene alterations (HRRm). Broad differential efficacy benefit was evident for TALA + ENZA vs PBO + ENZA across multiple molecular subgroups and was most pronounced for the BRCA1-PALB2-BRCA2 axis and CDK12. Additional analyses are warranted. Clinical trial information: NCT03395197.

Clinical Trial Registration Number: NCT03016312 Background: IMbassador250 (IM250) was a prospective phase III trial which showed no overall survival (OS) benefit for adding atezolizumab to enzalutamide for men with mCRPC who had prior progression on abiraterone. Here we report on a new tumor-naïve monitoring assay (F1M) for molecular response assessment which is based on ctDNA TF detection and dynamics. TF detection at C3D1 was linked to unfavorable outcomes and identified early progression post-abiraterone, with increased information derived from TF detection at baseline. TF on F1M thus complements PSA testing, which had a lower PPV for identifying early progression than ctDNA.

In the all-comers cohort, talazoparib (TALA) + enzalutamide (ENZA) as first-line treatment for pts with mCRPC significantly improved rPFS vs ENZA (HR 0.63; 95% CI 0.51–0.78). The statistically significant rPFS improvement in the TP-2 all-comer ITT population did not seem to be attributable to pts with undetected BRCA/HRR alterations. There was evidence of rPFS benefit in the non-BRCAm and non-HRRm subgroups in favor of TALA + ENZA. While the OS data are still maturing, there is a clear benefit for pts with BRCAm and no detrimental impact for pts negative for BRCAm or HRRm by both tumor and ctDNA.

The results showed a similar trend to previous studies, where FGFR GA was reported in approximately 20% of metastatic UC patients. No difference was found in the PFS and the estimated survival rate by FGFR2/3 GA-positive or -negative patients. Our data showed that treatment pressure did not alter the FGFR status commonly.

In contrast to some prior literature, this study reports detection of a wide variety of rearrangements in ctDNA. The prevalence of driver rearrangements in tissue and LBx was comparable when TF ≥1%. LBx presents a viable alternative when TBx is not available, and there may be less value in confirmatory testing when TF is sufficient.

The detected variants should be re-annotated due to the inclusion of several benign variants in the CGP testing, and the landscape of the variants derived from these results in the CGP testing, including FoundationOne CDx, FoundationOne Liquid CDx, and OncoGuide, will help researchers and physicians interpret these results.

This study reports on the largest set of LBx from pts likely exposed to anti-EGFR published to date. LBx can provide a more comprehensive and quantitative picture of acquired resistance to anti-EGFR in CRC than tissue biopsy, including some potential novel mechanisms identified in this study. Further investigation into whether detection of resistance can inform clinical decisions about timing of anti-EGFR mAb use and rechallenge is warranted.

The circulating VAF of RAS genes enables to split RAS mutant-Low (favorable prognosis similar to RAS/BRAF wild-type) from RAS mutant-High (poorer prognosis similar to BRAF mutant) metastatic colorectal cancer. These results provide further insights into prognostication and therapeutic strategies in patients with RAS mutant metastatic colorectal cancer.

ctDNA TF is a prognostic biomarker in mPDAC with potential to inform expected longevity of patients. Uniform cohorts, with regard to treatments given and line of therapy, would help further evaluate the ability of ctDNA TF to identify patients with aggressive disease and inform the design of future studies to personalize therapeutic decision-making.

HER2 amplifications were found in 10% of advanced BTC and did not represent an independent predictive factor for OS. Of clinical significance, patients with HER2-amplified BTC derive a significant benefit from anti-HER2 therapy.

Our nationwide molecular profiling project has facilitated the enrollment of patients with advanced gastrointestinal cancers in clinical trials. Furthermore, it demonstrated a survival benefit by providing patients matching targeted therapy.

There was no pts treated with durvalumab plus gemcitabine and cisplatin. Two pts with TP53/KRAS alteration and MSI-High received pembrolizumab monotherapy, and partial response was achieved with a progression-free survival of 9.4 and 22.0 months... Patients with advanced BTC with co-occurring TP53/KRAS alterations have worse prognosis. Interestingly, the presence of these co-alterations was associated with a higher likelihood of MSI-High phenotype.

P3; Trial completion date: Apr 2027 --> Aug 2027 | Trial primary completion date: Dec 2024 --> Sep 2025

Gounder showed thar CGP could lead to refinement or reassignment of 10.5% of diagnoses and 32% of the patients harbored potentially actionable alterations. In this study, 2.8% of patients were reclassified and the actionable gene mutations were found in 25% of the patients with sarcoma by the CGP. Although few patients could receive genotype-matched therapy, they could achieve relatively good control.

Continuous values distributions by category were tested using the Mann-Whitney U-test, and a threshold was set with ROC curve analysis using Youden's Index. High and low groups were defined using this cutoff, and a

"Foundation Medicine, Inc., and Pierre Fabre Laboratories today announced a collaboration to develop Foundation Medicine’s high-quality genomic tests, FoundationOne^®CDx and FoundationOne^®Liquid CDx, as companion diagnostics for new targeted therapies to treat patients with non-small cell lung cancer (NSCLC). The companies will work collaboratively to seek the regulatory approval for Foundation Medicine assays which detect mutations including BRAFV600E to identify patients for potential treatment with Pierre Fabre Laboratories’s BRAF/MEK inhibitor combination regimen, BRAFTOVI^® (encorafenib) and MEKTOVI^® (binimetinib), in the European Union."

A single patient with microsatellite instability was identified, in the mHSPC subgroup. Conclusions Diagnosis of actionable mutations in metastatic prostate cancer patients could allow targeted treatments, justifying genetic testing in this population.

Three HER2-negative patients were prescribed anti-HER2 therapy for ERBB2 amplification, one patient was prescribed entrectinib for NTRK fusion, and three patients participated in clinical trial for ERBB2 mutation and FGFR1 rearrangement. If ESCAT ranking beyond I/II and recommended therapy from FoundationOne report (e.g Abemaciclib for CCND1 amplification, Everolimus for PTEN loss)are added, 64 pts (60.1%) were considered these treatments, and 19 pts (18.1%) actually received these treatment...Low accessibility of ESCAT ranking I/II MT may be because, in Japan, CGP testing is available only for patients who have completed or are expected to complete standard therapy. Early use of CGP testing and an increase in clinical trials will be desirable in Japan.

In the NIMBUS trial, all pts with PR to NIVO plus low dose IPI had a TMB > 20 Mut/Mb and had a decrease in TMB during treatment. ESR1 and PTEN mutations were associated with lack of benefit, while PALB2 mutation was associated with increased benefit. If validated, these results could help tailor the use of ICI among pts with TMB-H MBC.

CGP detects a wide spectrum of mutations in ESR1, including missense and indel mutations and fusions. When LBx TF is < 1%, sensitivity for ESR1mut is reduced and repeat testing should be considered. ESR1mut can coexist with complementary or competing resistance mechanisms, particularly when ESR1 is a minor allele, which could impact benefit from novel ET approved for patients with ESR1 mutations.

Prior fulvestrant (FUL) was received by 53% of patients in the GIR + INAVO arm (n = 8). Safety summary Data are % of patients. AE, adverse event; GIR, giredestrant; INAVO, inavolisib; TRAE, treatment-related adverse event; tx, treatment.