Around the Globe

Changing the Game in Oncology Development
DIA Global Oncology Development 2020

Eri Sekine
Novartis Pharma K.K.


he world surrounding cancer treatment continues to evolve rapidly. Emerging products now include immuno-oncology drugs and other new regenerative medicine and medical device therapies which further expand therapeutic choices in cancer treatment. Thanks to rapidly evolving digital applications, such as artificial intelligence (AI) and the Internet of Things (IoT), and their impact on clinical trial operations, clinical development in oncology faces both challenges and opportunities in keeping the evaluation of novel therapeutic products simple and reliable.

Contributing to this global tide, DIA Global Oncology Development 2020, co-chaired by Noboru Yamamoto (National Cancer Center Hospital) and Toshihiko Doi (National Cancer Center Hospital East) and convened in Tokyo this past January, was the first DIA Japan workshop to specifically focus on this therapeutic area. Strong energy to innovate, and recognition of difficulties along the path to innovation, were both evident throughout this workshop. New science and technology are already evident in Japan, but it will take collaboration across academia, regulatory, and industry, from basic research to clinical trials, to deliver innovation to patients.

In his opening lecture, Expectation to Oncology Treatment Development, Tomomitsu Hotta (Honorary President, National Cancer Center Hospital) summarized efforts in Japan during the past decade to strengthen the bridge between basic research and clinical studies, and to accelerate the development of practical applications for cancer diagnosis and treatment. These examples include the Japan Cancer Research Project he leads for AMED (Japan Agency for Medical Research and Development), which has already generated positive outcomes in pediatric and other rare cancers. He urged a stronger collaboration on Japanese assets among professionals in academic research, regulatory science, and industry.

PMDA Direction for Oncology Drug Development

Pharmaceuticals and Medical Devices Agency (PMDA) Chief Executive Yasuhiro Fujiwara shared his personal view of PMDA Direction for Oncology Drug Development and its basic policy of “4Fs” or “four Firsts:” Patients First, Access First, Safety First, and Asia First. Sensible scientific balance of benefit and risk, expediting NDA review time, and transparently sharing accurate information among study sites are also essential in the daily clinical setting, he noted. PMDA has shortened review times and introduced new regulatory frameworks such as Sakigake and Regulatory Science Consultation to support rapid drug approval. PMDA also promises to maximize the value of new tools and technologies such as immuno-oncology, genomics, and real world data to bring new treatments to patients as quickly as possible.

Innovation in Oncology Therapies

Experience in oncolytic viruses, CAR-T, and genomic medicine were discussed as examples of growing diversity in oncology development strategy. Because these and other advanced therapies are so different and unique from so many different perspectives—scientific characteristics, efficacy, toxicology, safety in development and after launch, pharmacokinetics, quality/manufacturing, etc.—bringing these therapies from basic research to clinical trials to practical use is definitely complicated work. However, these therapies do share one common trait: They are so advanced that no single company can effectively discover, develop, and deliver them; collaboration among stakeholders (including regulators) is one of their most important success factors.

Operational Challenges in Oncology Clinical Trials

While the clinical trial environment has improved in Japan in recent years, productivity remains lower than in other regions and many lessons can be learned from oncology clinical trials in China, Korea, Malaysia, and Taiwan. But Japan’s research and industry frameworks can provide robust platforms for first-in-human studies and access to global development for compounds originating in Japan.

Decentralized clinical trials are a hot topic in Japan and interest is growing in the technologies required to implement them. Technology can also help improve efficiency in trials conducted with limited resources by supporting site staff with data exchange between systems, artificial intelligence (AI) navigation in data entry, remote data access, and electronic data archives. Research shows that 70 percent of patients currently enrolled in phase 1 studies travel from an area within one to two hours of that site. Patients who live farther away have fewer treatment options. The challenge is to identify truly transformational technologies, and where and how to implement them, to enable these trials and meet the needs of all these people.

A “patient-requested medical care system” is to be used as a “Ukezara study” for a short-term solution to individualized care. (“Ukezara” means a plate to save drops from falling when drinking coffee or tea.) For example, when oncology panel diagnostics identify a genomic mutation target in a patient, that patient often cannot find a suitable clinical trial in which to enroll. With no other clinical pathways, a “patient-requested medical care system” is one of a very small number of individualized treatment options.  This solution cannot be sustained and highlights the need for more long-term solutions.

Panel Discussion

The closing panel discussion started with post-launch safety management of a new drug approved with limited clinical data, which often happens in therapeutic areas such as cancer. Stakeholder communication and collaboration in these situations are essential. From the sponsor and manufacturer perspectives, knowledge accumulated by the development team must be delivered to the commercialization team to ensure proper safety management. Data accumulation after launch is critical to drug safety strategies. Meaningful post-market clinical trials conducted not only by sponsors but by academia, and a system to share their findings, would be most helpful.

Utilization of real world data (RWD) in drug development is another “hot” topic in Japan, and this discussion centered around the reliability of RWD as a random sample from certain patient groups. Panelists also shared their experience with the difficulty of considering patient benefit and risk in cases of Conditional Approval using phase 2 study data, and the assumption that new drugs do not always improve the current standard of care.

Yasuhiro Fujiwara (PMDA), Fumi Yamamoto (Ministry of Health, Labour and Welfare), Toshihiko Doi (National Cancer Center Hospital East), and Toshio Shimizu (National Cancer Center Hospital), served as discussion panelists.

The author and editor wish to especially acknowledge these contributors to this program:
Program Co-Chairs Toshihiko Doi (National Cancer Center Hospital East) and Noboru Yamamoto (National Cancer Center Hospital)

Program Committee Members Masakazu Hirata (PMDA), Toshiko Ishibashi (Ono Pharmaceutical Co., Ltd.), Takuya Suzuki (Eisai Co., Ltd.), Tomoko Takami (MSD K.K.), and Atsushi Tsukamoto (Daiichi Sankyo Co., Ltd.)

Program Advisors Hironobu Saito (Daiichi Sankyo Co., Ltd.) and Junko Sato (PMDA)

DIA Japan Operations: Akina Takami (PMDA)

All DIA Global Oncology Development 2020 speakers