This article has been updated to provide greater clarity on the comparisons made in the Liquik study.
NEW YORK – Precision oncology company Lucence plans to present interim results from the ongoing Liquik liquid biopsy lung cancer study and data pointing toward the potential benefits of cell-free RNA testing for earlier cancer detection at the World Congress for Lung Cancer in Singapore later this week.
In one study, to be presented on a poster, the Palo Alto, California-based company showed that its LiquidHallmark liquid biopsy cancer biomarker test, which detects alterations in 80 genes, had high concordance with tissue biopsy results in patients with advanced non-small cell lung cancer (NSCLC). It also detected lung cancer biomarkers in slightly more patients than Guardant Health's Guardant360 test.
Another study, to be presented on a separate poster, demonstrated that plasma cfRNA abundance increased in both early- and late-stage lung cancers while plasma cfDNA abundance only rose in late-stage cancers, suggesting that a cfRNA test might be able to detect the cancer earlier. That study used an amplicon panel targeting 24 mRNAs and lncRNAs with expression specific to lung cancer patients.
The company's liquid biopsy assays, targeting cfDNA and cfRNA, use a proprietary amplicon-based sequencing technology called AmpliMark.
"[We] present evidence that AmpliMark’s liquid biopsy technology can benefit lung cancer patients across the full spectrum of care, from screening to therapy selection, by identifying more meaningful targets on both [circulating tumor] DNA and [circulating tumor] RNA," Lucence CEO Min-Han Tan said by email.
The interim results from the Liquik study come from 120 patients enrolled in the study as of November 2022 at locations in both the US and Singapore, all of whom were treatment-naïve, with metastatic non-squamous NSCLC. The firm had previously presented interim results from 60 participants at the International Society of Liquid Biopsy Congress in Miami last year.
Results so far show approximately 93 percent to 100 percent concordance between LiquidHallmark and tissue-based profiling across nine National Comprehensive Cancer Network (NCCN) guideline-recommended biomarkers: EGFR, ALK, RET, ROS1, NTRK fusions, MET, BRAF, ERBB2, and KRAS.
While tissue-based sequencing identified at least one biomarker in 65 out of the 120 patients, LiquidHallmark detected at least one biomarker in 60 individuals.
In a head-to-head comparison with the Guardant360 liquid biopsy test among the 65 study participants with positive tissue testing results, LiquidHallmark detected at least one NCCN biomarker in 47 patients, while Guardant360 detected at least one biomarker in 43 patients.
Overall, tissue testing identified 67 biomarkers in the 65 patients, of which LiquidHallmark detected 50 and Guardant360 found 43.
Also, each liquid biopsy assay independently detected biomarkers in 13 patients that had tissue-negative results or insufficient tissue available.
Nonetheless, Tan commented that "no formal statistical comparison between LiquidHallmark and Guardant360 has been yet reported at this interim analysis," he said, "but I certainly look forward to the final study comparison."
Although it remains too early to calculate statistical significance, Tan said that the observed detection difference between LiquidHallmark and Guardant360 is nonetheless useful to consider. "For the actionable biomarkers, the difference observed was 16.3 percent (50 vs. 43). Every such actionable biomarker detected by liquid biopsy corresponds to an additional potential therapeutic option for patients."
Tan said that the interim results should provide oncologists with useful insights on the performance of LiquidHallmark, adding that he expects the Liquik study and all necessary follow-up to be completed in December of next year.
"We expect to share more results at the 2023 North American Conference on Lung Cancer," he said. "The report then is expected to include, for the first time, prospective data on circulating tumor RNA in lung cancer."
Lucence has recently been exploring the addition of ctRNA to its LiquidHallmark platform.
In its data presented at WCLC, Lucence showed that cfRNA abundance, measured by the company's amplicon-based platform, increased in both early- and late-stage lung cancers, compared to normal controls, though the results were not statistically significant. Meanwhile, cfDNA concentration only increased in late-stage but not early-state cancers, compared to controls. Concurrent with this finding, company researchers showed that cancer-related mutations spiked only in late-stage cancer for cfDNA, while cancer-related cfRNA expression was elevated across all cancer stages.
This result is consistent with the reasons for finding each type of cancer-related nucleic acid in the blood, according to David Spetzler, president of Caris Life Sciences. "When a cell loses its DNA, that is a catastrophic event for the cell," he said. "That's cell death."
Living cells, on the other hand, constantly shed RNA, making it a more logical biomarker of early-stage cancers, whose cells are more often living and reproducing compared to cells at later cancer stages, he explained. "So we find [that] the majority of the RNA signal is coming from circulating microparticles, extracellular vesicles, exosomes, whatever."
This RNA often encodes genes related to controlling the cancer's environment, Spetzler added, such as through immune evasion, angiogenesis, and metastatic niche preparation.
Caris has been developing its own ctDNA and ctRNA combined cancer profiling assay, Caris Assure. Although currently used only for therapy selection, Spetzler said that the company has completed sample collection for a minimal residual disease trial. Those samples will be analyzed over the coming months, and the company has enrolled nearly 15,000 participants into its ongoing early cancer detection studies.
Although the assay is currently marketed as a lab-developed test, Caris expects to eventually seek approval for the test from the US Food and Drug Administration.
Lucence is also eyeing further commercial availability of LiquidHallmark, which Tan said should be helped considerably by the addition of ctRNA.
"Our next step for ctRNA is to develop evidence in support of Medicare reimbursement for ctRNA by Q3 2024, to follow LiquidHallmark's Medicare reimbursement coverage for ctDNA in February 2023," Tan said.
While studies are ongoing, Lucence continues to expand the panel of genes included in LiquidHallmark, as well as the assay's distribution. The company expanded the number of ctRNA targets on its panel from 27 to 36 genes in April and inked a deal with Omnigen last year to distribute the assay in Turkey.
Additionally, Lucence is working to establish clinical validity of ctRNA in plasma for screening.
"The WCLC abstract on early lung cancer detection highlights the potential utility of this approach," Tan said.