This story has been updated to include additional information about the Canhelp-Origin test.
NEW YORK – Chinese molecular diagnostics company Canhelp Genomics is seeking strategic partnerships to help secure regulatory approval in the US and other countries for its 90-gene expression assay, Canhelp-Origin, following the publication of results demonstrating the test's effectiveness for guiding therapy in Chinese patients with cancer of unknown primary (CUP).
In the meantime, the company is also conducting additional studies to further demonstrate the test's utility for this indication, as well as to help inform treatment in male breast cancer and in other ethnicities.
In 2022, Canhelp-Origin received China National Medical Products Administration approval and an EU CE mark for human tumor origin classification. The test distinguishes 21 tumor types which comprise 95 percent of all solid tumors. The assay measures messenger RNA expression patterns of 90-tumor specific genes from formalin-fixed paraffin-embedded tumor samples simultaneously using the Thermo Fisher ABI 7500 real-time PCR system and assigns a tissue of origin to tumors using data analysis software.
In China, Canhelp conducts all testing steps on test kits returned by clinics. The company is considering both laboratory-developed and in vitro diagnostic test kit models for global distribution, depending on country and market, and is working to expand the list of compatible real-time PCR platforms.
In a multicenter validation study, the Hangzhou-based company demonstrated the test had 94.4 percent accuracy and 99 percent specificity. The test has also shown more than 90 percent diagnostic accuracy in other pan-cancer studies and in certain tumor types such as metastatic brain and liver cancer.
Patients with CUP, or occult cancers, have histologically confirmed metastatic tumors for which a primary site cannot be identified. They account for around 2 percent to 9 percent of tumors and have a poor prognosis, with median survival ranging from six months to nine months. Having already established the validity of Canhelp-Origin for diagnosing various tumor types, the company aimed to show that it could be reliably used to guide therapy.
In results from the Phase III Fudan CUP-001 trial published in Lancet Oncology last week, and presented at the European Society for Medical Oncology Congress in October 2023, patients with CUP whose treatment was guided by Canhelp-Origin had median progression-free survival of 9.6 months versus 6.6 months for those who received empirical chemotherapy. Median overall survival was 28.2 months in the site-specific therapy group and 19.0 months in the empirical chemotherapy group. In the site-specific therapy group, 46 out of 82 patients who initiated treatment, or 56 percent, had grade 3 or worse treatment-related adverse events, compared with 52 out of 85 patients, or 61 percent, in the empirical chemotherapy group.
Canhelp researchers enrolled 182 patients with CUP at the Fudan University Shanghai Cancer Center between September 2017 and February 2021. All patients received a standard diagnostic workup. Upon receipt of the Canhelp-Origin assay results, researchers conducted additional biomarker testing, if indicated by the results. For example, patients whose results suggested breast cancer as an origin also received testing for estrogen and progesterone receptor sensitivity and HER2 status.
Patients then received standard treatment for predicted tumor types, including targeted therapies for those with genomic alterations, according to practice guidelines. Patients whose results did not determine a tissue of origin received empirical chemotherapy every three weeks until disease progression. The most commonly predicted tissues of origin in the study were gastroesophageal, lung, ovary, cervix, and breast.
Canhelp CEO Qinghua Xu said the trial is the first randomized study to show that using a primary site classifier based on gene expression profiling improves the prognosis for patients with CUP. "It supports the hypothesis that CUP is composed of multiple cancers of known primary, rather than being an independent cancer entity," Xu said, adding that the use of a tissue origin test like Canhelp-Origin could become the new standard of care in patients with CUP by providing more accurate and early diagnoses of difficult-to-diagnose cancers.
"The Fudan CUP-001 trial is not just a milestone for Canhelp Genomics in terms of clinical validation but also a strategic move that can propel the company's growth and impact in the global healthcare landscape," he said.
Canhelp is following Fudan CUP-001 with several further studies and expects to publish results from those later this year. In the Phase III CUP-001 trial, researchers are exploring the clinical utility of Canhelp-Origin for diagnosis and management of patients with cancer of unknown or unclear primary.
For this study, researchers enrolled more than 300 patients at Fudan University who received the test between February 2023 and December 2023 and collected data including demographics, clinical characteristics, and pathologic features. The test turned up 21 tumor types among 295 patients who met all inclusion criteria. The most common cancers were gastroesophageal, lung, breast, head and neck, and ovarian cancer. In early results presented at the American Society of Clinical Oncology's annual meeting in May, the company said the study affirms the clinical utility of the test as a standard diagnostic approach for CUP.
In another ongoing clinical study, the company aims to validate Canhelp-Origin in male breast cancer. According to Xu, most male patients with breast cancer are diagnosed at advanced stages of disease due to factors including insufficient health education and reluctance to seek medical attention. In assay results from 30 male patients with primary or metastatic breast cancer, researchers have found that Canhelp-Origin has a very high overall accuracy compared with pathological diagnosis.
Lastly, Canhelp is working to evaluate Canhelp-Origin in other ethnic groups through studies it is conducting in collaboration with Ain Shams University in Cairo. In approximately 100 cancer cases including tumor types common in Egypt, the test demonstrated a high level of agreement with the reference diagnosis, achieving more than 90 percent concordance across all specimens. "We are planning to validate the test in other ethnic groups on other continents," Xu said, "but the details are not finalized yet."
Xu said Canhelp would like to establish strategic partnerships aimed at securing FDA approval in the US and registrations in other countries. In addition, the company is seeking NMPA registration and global strategic partnerships for a multitarget urine RNA test, Canhelp-UriBLAD, for noninvasive detection and surveillance of urothelial carcinoma.