MASTER KEY Project: Powering Clinical Development for Rare Cancers Through a Platform Trial

Hitomi S Okuma, Kan Yonemori, Shoko N Narita, Tamie Sukigara, Akihiro Hirakawa, Toshio Shimizu, Taro Shibata, Akira Kawai, Noboru Yamamoto, Kenichi Nakamura, Toshiro Nishida, Yasuhiro Fujiwara, Hitomi S Okuma, Kan Yonemori, Shoko N Narita, Tamie Sukigara, Akihiro Hirakawa, Toshio Shimizu, Taro Shibata, Akira Kawai, Noboru Yamamoto, Kenichi Nakamura, Toshiro Nishida, Yasuhiro Fujiwara

Abstract

For rare cancers, challenges in establishing standard therapies are greater than those for major cancers, and effective methods are needed. MASTER KEY Project is a multicenter study based in Japan, with two main parts: prospective registry study and multiple clinical trials. Advanced rare cancers, cancers of unknown primary origin, and those with rare tissue subtypes of common cancers are targeted. The registry study accumulates highly reliable consecutive data that can be used for future drug development. The multiple trials are conducted simultaneously, targeting either a specific biomarker or a rare tumor type of interest. The first interim data set from the registry part presented here shows the prevalence of genetic abnormalities, response rates, survival rates, and clinical trial enrollment rates. From May 2017 to April 2019, 560 patients (mean age = 53) were enrolled in the project. Frequent cancer types included soft tissue sarcomas, neuroendocrine tumors, and central nervous system tumors. Among the 528 patients with assessable data, 69% (364/528) had next-generation sequencing tests, with 48% (176/364) harboring an "actionable" alteration. Seventy-one (13%) patients have been enrolled in one of the clinical trials, with an accrual rate of 3.94 patients/month. A descriptive analysis of biomarker-directed or non-biomarker-directed treatment survival was performed. This project is expected to accelerate development of treatments for rare cancers and show that comprehensive platform trials are an advantageous strategy.

Conflict of interest statement

All authors report grants for the institute from multiple companies participating in this project during the conduct of the study. Outside of the present study, the following authors report grants and/or other payments: A.H. reports grants and personal fees from Ono Pharmaceutical; personal fees from Astellas Pharma, Abbvie, Nippon Boehringer Ingelheim, Kissei Pharmaceutical, Pfizer, and Nippon Shinyaku. A.K. reports personal fees from Eli Lilly, Taiho Pharmaceutical, Novartis, Takara, and Eisai. K.Y. reports personal fees from Eisai, Novartis, Taiho Pharmaceutical, Pfizer, and AstraZeneca; grants and personal fees from Ono Pharmaceutical; and grants from Daiichi Sankyo. K.N. reports personal fees from Chugai Pharmaceutical, Taiho Pharmaceutical, and Bayer. T.N. reports grants from Pfizer, other payments from Novartis, Bayer, Eisai, and Taiho Pharmaceutical. T.Shim. reports grants from Novartis, Eli Lilly, Daiichi Sankyo, Bristol‐Myers Squibb, Eisai, AbbVie, AstraZeneca, Takeda Oncology, Incyte, Chordia Therapeutics, 3D‐Medicine, from Symbio Pharmaceuticals, PharmaMar, Five Prime, and Astellas Pharma; and personal fees from Taiho Pharmaceutical, Boehringer Ingelheim, Chugai Pharmaceuticals, and Ono Pharmaceutical. N.Y. reports grants from Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, Eli Lilly, Quintiles, Astellas Pharma, Bristol‐Myers Squibb, Novartis, Daiichi Sankyo, Pfizer, Boehringer Ingelheim, Kyowa‐Hakko Kirin, Bayer, Ono Pharmaceutical, Janssen Pharma, MSD, Merck, and Takeda; and personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Pfizer, Eli Lilly, Bristol‐Myers Squibb, Eisai, Otsuka, Takeda, Boehringer Ingelheim, Cimic, and Sysmex. Y.F. reports grants and other payments from Japan Agency for Medical Research and Development, grants and other payments from The Ministry of Health Labor and Welfare of Japan, during the conduct of the study; and other payments from AstraZeneca, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical, Novartis Pharma, SRL Inc, and Bristol‐Myers Squibb and contributed to the study until March 2019. All other authors declared no competing interest for this work.

© 2020 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Figures

Figure 1
Figure 1
MASTER KEY Project overview. IHC, immunohistochemistry; MK, Master Key; NGS, next‐generation sequencing.
Figure 2
Figure 2
Cancer types and gene alterations in NGS testing. (a) Number of enrolled patients by cancer type (n = 528). (b) Overall alterations in the 364 patients in NGS testing. Mutations, amplifications, fusions, and deletions are distinguished by color. (c) Genes classified according to potential clinical “actionability” by level of evidence. CNS, central nervous system; NGS, next‐generation sequencing; PNS, peripheral nervous system.
Figure 3
Figure 3
Kaplan‐Meier survival curves for progression‐free survival are plotted for (a) overall population with at least 6 months of follow‐up, (b) those receiving clinical trial therapy and routine clinical practice therapy, (c) those receiving biomarker‐directed therapy and non‐biomarker‐directed therapy. CI, confidence interval; CNS, central nervous system; CUP, carcinoma of unknown primary; FDA, US Food and Drug Administration; M. MENINGIOMA, malignant meningioma; PFS, progression‐free survival; PNS, peripheral nervous system.

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