Progress report of a cross-organ and biomarker-based platform study: BELIEVE trial NCCH1901.

Abstract

TPS1611 Background: Cancer Genomic Medicine (CGM) has been developing and more patients have received the comprehensive genomic profiling (GCP) test under national healthcare system in Japan. However, the number of patients who could receive the genomically matched therapy based on the results of CGP tests was limited. To improve the drug accessibility, we initiated a cross-organ, biomarker-based clinical trial (NCCH1901, the BELIEVE trial). It was a platform trial and could be considered as the Japanese counterpart to the National Cancer Institute's Molecular Analysis for Therapy Choice (NCI-MATCH) study in the United States. Methods: It was a multi-institutional joint research nationwide led by NCCH with a master’s protocol. Several drug cohorts were pre-established, allowing patients to participate in molecularly targeted treatments recommended as a result of CGP test. All drugs were provided for free from the pharmaceutical companies. The objective of this trial was to administer off-label drugs for the respective genomic abnormalities and collect efficacy and safety data for patients of the drugs. The primary endpoint was the response rate based on the best overall response for up to 16 weeks. This trial has been conducted under both of the Japanese Clinical Trial Act and the patient-proposed healthcare services which enable patients to receive unapproved, off-label drugs partially covered by National Health Insurance. The protocol and the informed consent forms were approved by the National Cancer Center Hospital (NCCH) certified review board and the Ministry of Health, Labour and Welfare (MHLW). The trial was registered in the Japan Registry of Clinical Trials (jRCTs031190104). As of January 31, 2023, we have 20 drug cohorts and the planned number of enrollments for each cohort was 50 with the target lesions and 30 without the target lesions. There were more than 500 patients so far. The most common cancer was brain tumours, followed by carcinoma of endocrine organs and the colorectal cancer. BRAF mutation and ERBB2 amplification were the frequent genomic abnormalities registered in this trial. Five drug cohorts have already finished recruiting and 2 drug cohorts assessed their efficacies. We are still continuing to discuss several pharmaceutical companies to increase the drugs cohorts in this platform. This trial is now recruiting the patients and is contributing significantly to increase the treatment opportunity for the cancer patients. Clinical trial information: jRCTs031190104 .