A multicohort platform trial to improve drug access for pediatric cancer patients in Japan: The PARTNER trial (NCCH2220).

person Bunpei Miyazaki Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan info_outline Bunpei Miyazaki, Nami Shirakawa, Minako Sugiyama, Ayumu Arakawa, Yayoi Ando, Kenta Anjo, Yoko Kai, Yukari Hoshina, Junki Mizusawa, Taro Shibata, Haruhiko Fukuda, Natsuko Tsuda Okita, Kenichi Nakamura, Chitose Ogawa

Authors person Bunpei Miyazaki Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan info_outline Bunpei Miyazaki, Nami Shirakawa, Minako Sugiyama, Ayumu Arakawa, Yayoi Ando, Kenta Anjo, Yoko Kai, Yukari Hoshina, Junki Mizusawa, Taro Shibata, Haruhiko Fukuda, Natsuko Tsuda Okita, Kenichi Nakamura, Chitose Ogawa Organizations Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan, Clinical Research Support Office, National Cancer Center Hospital, Tokyo, Japan Abstract Disclosures Research Funding No funding sources reported Background: In Japan, there are no pediatric regulations that encourage drug development for pediatric cancer, such as Pediatric Investigation Plans (PIPs) which are mandated in Europe, or the RACE Act in the U.S. Therefore, there are fewer early-phase clinical trials and approved drugs for pediatric cancer than in Western countries. In addition, because there is no rapid compassionate use program, there are delays when using an unapproved drug. According to a report from the Japanese cancer genome profiling (CGP) testing data center, C-CAT, 51.3% of pediatric patients with solid tumors had targetable genetic abnormalities. However, only 5.8% of them had access to the recommended molecular targeted therapy (Tanimura K. et al., presented at the Japanese Society of Pediatric Hematology and Oncology annual meeting 2022). Thus, Japanese pediatric patients with relapsed or refractory solid tumors have limited access to novel drugs, even if they have druggable mutations. Therefore, we designed a platform study (NCCH2220, PARTNER trial) to rapidly deliver molecularly targeted drugs based on CGP testing. Methods: This study has two objectives: first, to administer some drugs to pediatric patients that are not approved for pediatric cancer in Japan. These drugs have been shown to be safe in pediatric patients in foreign countries and are expected to be effective. Second, to evaluate the safety and efficacy of the drug in Japanese pediatric patients and, if necessary, its pharmacokinetics. These data will be used for potential future regulatory filings. This is an open-label, multicenter, multicohort study. Eligible patients are aged 0–29 years with diseases having no standard therapy, which are refractory, or when there is intolerance to standard therapy. The study drug must be recommended for the patient by CGP testing or approved for pediatric use for their disease in the U.S. or Europe, or approved in Japan for use in adults only. The drugs are used as monotherapy in the study. The study schedules follow a master protocol. Up to 30 patients can be enrolled in each cohort. The primary endpoint is the incidence of dose-limiting toxicity in each cohort. The secondary endpoints are the incidence of adverse events, the overall response rate, and, if necessary, the pharmacokinetics in each cohort. As of January 2024, the study had five treatment cohorts with the following agents: imatinib, pazopanib, ruxolitinib, trametinib, and atezolizumab. Additional cohorts will be added. We started planning the study in November 2022, and enrollment began on January 18, 2024. This platform trial has enabled us to deliver drugs to patients more quickly and efficiently than by conducting individual early-phase trials for each drug. Clinical trial information: jRCTs031230544 .

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