TEST:

OncoScreen Plus®

Furthermore, functional experiments demonstrated that silencing CARD11 and GATA2 impairs HR repair efficiency and enhances the sensitivity of tumor cells to olaparib treatment. In summary, in the absence of mutations in the HR genes, the sensitivity of tumor cells to PARP inhibitors and platinum-based chemotherapy may be enhanced in a subset of breast cancer patients with LNGC somatic mutations.

The most frequent AEs with C + F were diarrhoea (60.6% vs 11.3% P + F) and hyperglycaemia (57.7% vs 17.7%); the most frequent grade ≥3 AEs were rash maculopapular (8.5% vs 0%), rash and diarrhoea (both 7.0% vs 0%); grade ≥3 hyperglycaemia was 1.4% vs 0%. AEs leading to C/F discontinuation were reported in 11.3% for C + F vs 3.2% for P + F. Conclusions Similar to the Global population, the benefit–risk profile of C + F in the Chinese cohort appears favourable; no new safety concerns with C + F were identified.

Conclusions The combination of RNA- and DNA-based NGS provides information about molecular alterations for the management of patients with CNS tumors. Those with actionable gene fusions or other alterations may benefit from target therapy, especially in the setting of limited choice of treatments.

"Burning Rock Biotech Limited...is pleased to announce that our flagship comprehensive genomic profiling (CGP) product, OncoScreen Plus, was featured in a phase 3 multi-regional clinical trial (MRCT), along with FoundationOneCDx, in support of advancement in breast cancer treatment...In the study, Burning Rock's flagship comprehensive genomic profiling (CGP) product, OncoScreen Plus, was used to determine activating mutations in PIK3CA and AKT1 and inactivating alterations in PTEN genes for patients enrolled in China."

P3 | "TMB status may play a role in predicting clinical outcomes in pts with advanced ESCC treated with TIS versus ICC, especially when a higher TMB cutoff is chosen. These findings need further prospective validation.Table. Clinical outcomes by TMB status (cutoff 10 mut/Mb)TMB statusTMB-HTMB-LTreatmentTISICCTISICCn (% in TMB BEP, N=209)27 (12.9)31 (14.8)78 (37.3)73 (34.9)ORR, % (95% CI)33.3 (16.5, 54.0)6.5 (0.8, 21.4)16.7 (9.2, 26.8)17.8 (9.8, 28.5)Median PFS, months (95% CI)2.4 (1.4, 5.5)2.3 (1.3, 2.9)1.4 (1.3, 2.7)2.7 (1.5, 3.3)PFS HR (95% CI)0.52 (0.28, 0.97)1.06 (0.73, 1.53)Interaction p-value0.0537Median OS, months (95% CI)6.1 (4.2, 18.6)4.7 (3.4, 7.0)8.6 (4.6, 11.8)7.0 (4.6, 8.6)OS HR (95% CI)0.58 (0.32, 1.04)0.72 (0.50, 1.03)Interaction p-value0.5374TMB-adjusted OS HR (95% CI)0.68 (0.5, 0.92)BEP, biomarker evaluable population; CI, confidence interval; HR, hazard ratio; ICC, investigator chosen chemotherapy; OS, overall survival; PFS, progression-free survival;..."

FR ctDNA level is decreased from BL, and seems to correlate with clinical outcomes of 1L TIS in combination with chemotherapy in NSCLC; ctDNA has potential to be a surrogate biomarker for efficacy. This requires further prospective validation.Table.Analysis summary of ctDNA and PFS/OS by visitBaseline (BL)First response (FR)Study RATIONALE-304RATIONALE-307RATIONALE-304RATIONALE-307ctDNA UDDUDDUDDUDDn19578723284322mPFS, mo (95% CI)a9.23(5.75, 9.89)9.69(7.33, 14.52)NR(4.93, NR)9.76(7.52, 14.55)17.31(9.89, NR)9.20(3.71, 11.99)20.01(9.82, NR)9.56(7.39, 13.9)PFS HR (95% CI), UD/D1.14 (0.61, 2.21)0.40 (0.09, 1.73)0.16 (0.05, 0.5)0.54 (0.24, 1.21)PFS P-valueb 0.64210.22050.00190.1322mOS, mo (95% CI)NR(9.72, NR)NR(14,23, NR)NR(NR, NR)NR(16.89, NR)NR(NR, NR)18.78(9.92, NR)NR(NR, NR)NR(12.85, NR)OS HR (95% CI), UD/D1.04 (0.48, 2.25)NE0.16 (0.04, 0.69)0.48 (0.15, 1.51)OS P-valueb0.9254NE0.01470.2079aPrimary endpoint assessed by IRC; bP-values are reported for descriptive purposes only in this exploratory study.

Our study shows that NGS could efficiently facilitate the definitive diagnosis of ES and its mimics. We also revealed a diverse immune-genomic landscape of these SRCS, indicative of potential therapeutic opportunities targeting HRD and immune check-point in specific subtypes of these sarcoma entities.

The combination of RNA and DNA-based NGS techniques brings relevant information about tumor molecular alterations into the precision management of patients with bone and soft-tissue tumors. Those with tumors harboring targetable gene fusions and other alterations may benefit from target therapy, especially in the case of limited or exhausted standard therapy.

P2; Trial completion date: Apr 2023 --> Apr 2025 | Trial primary completion date: Oct 2022 --> Oct 2023

Further analysis showed that patients in GI-high group had higher tumor grade, aneuploidy and lower T cell infiltrations. Conclusions The one-stop method of GI index combined with POLE mutation offers more accurate and stable disease risk stratification and demonstrates the potential for guiding therapy for EC patients.

The present study is the first to report that the increase of bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.

The present study is the first to report that the increase of bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.

The method of classifying EC patients into four subgroups by NGS large panel provides similar clinical features to previous reports classified by other methods but is more convenient and stable. Furthermore, the method of combination of POLE mutations with HRD offers more accurate disease risk stratification and demonstrates the potential for directing therapy for EC patients.

Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.

P3 | "Here we report biomarker analysis of baseline tissue and blood TMB (tTMB and bTMB, respectively). Patients with nsq-NSCLC were randomized 2:1 to TIS + platinum + pemetrexed or platinum + pemetrexed. In this retrospective analysis, neither tTMB nor bTMB was significantly associated with PFS benefit, suggesting limited clinical utility of tTMB and bTMB in the setting of TIS + chemo as first-line therapy for advanced nsq-NSCLC."

P2; Trial primary completion date: Oct 2021 --> Oct 2022

P1/2 | "HA in the RTK-RAS-PI3K pathway may be associated with resistance mechanisms to anti-PD-1 therapy, even in patients with TMB-H tumors. Trial Registration NCT04068519"

Anlotinib plus sintilimab showed a promising efficacy with a favorable toxicity profile for pts with advanced CC. We will report more data in the future.

P2; Not yet recruiting --> Recruiting

Targeted RNA-seq can effectively identify genomic rearrangements that are undetectable by DNA-seq and provide lung adenocarcinoma patients with more opportunities for targeted therapy . Therefore, it should be recommended for all patients, in whom DNA-seq fails to detect driver alteration.

P2; N=41; Not yet recruiting; Sponsor:Zhujiang Hospital