武田薬品工業株式会社
Takeda today announced that the PARADIGM trial (Panitumumab and RAS, Diagnostically useful Gene Mutation for mCRC), a Phase III clinical study conducted in Japan, has met its primary endpoint. The PARADIGM trial is a randomized phase III study designed to compare the efficacy and safety of Panitumumab versus Bevacizumab, both used in combination with mFOLFOX6 in patients with previously untreated RAS wild-type mCRC.
Vectibix® (product name, generic name: panitumumab) is an anti-EGFR monoclonal antibody for the treatment of mCRC, which Takeda in-licensed from Amgen Inc. (Headquarters: Thousand Oaks, California, U.S., hereinafter, "Amgen").
Recently, primary tumor location is becoming an important prognostic and predictive factor in mCRC, and major guidelines recommend to take into account the primary tumor location as well as molecular biomarkers when choosing optimal treatment.
The PARADIGM trial is the first prospective study to evaluate the optimal treatment for patients with left-sided primary tumors (descending colon, sigmoid colon, rectum), RAS wild-type mCRC.
The topline results of the trial demonstrated that the panitumumab plus mFOLFOX6 resulted in statistically significant OS improvement in both left-sided primary tumor population and intent-to-treat population compared to the bevacizumab plus mFOLFOX6.
The safety profile of panitumumab in this study was the same as described on the current package insert.
“We are very pleased with the results of the PARADIGM trial. As there are an increasing number of treatment options for patients with mCRC, the significant results of this trial should allow us to provide a treatment option for patients with RAS wild-type mCRC. These results have the potential to greatly contribute to better outcomes for patients with RAS wild-type,” said Dr. Kei Muro, Director of Department of Clinical Oncology, and deputy director at Aichi Cancer Center Hospital, and Dr. Takayuki Yoshino, Director of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East, who chaired the steering committee for the trial.
“I would like to thank the many patients, their families and healthcare personnel who participated in the PARADIGM trial. A large-scale exploratory biomarker sub-study to identify potential biomarker candidates is also underway. We hope to contribute to better outcomes of mCRC and innovative drug development,” said Junpei Soeda, Head of Medical Affairs, Japan Oncology Business Unit.
Detailed results of the PARADIGM study will be reported in medical journals and presented at upcoming medical congress.
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Trial overview |
The objective of the trial was to compare the efficacy and safety of Panitumumab versus Bevacizumab, both used in combination with mFOLFOX6 in patients with previously untreated RAS wild-type mCRC |
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Trial design |
Multicenter, randomized, open label |
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Number of patients enrolled |
823 |
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Primary endpoint |
Overall survival (OS) |
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Secondary endpoints |
Progression-free survival (PFS), response rate (RR), duration of response (DOR) Curative resection ratio , Safety |
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Place of trial |
Japan |
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Biomarker sub-study |
The objective of this sub-study is to investigate potential biomarker candidates with oncogenic mutations using tumor tissue and circulating tumor DNA |
Vectibix® is approved by the FDA for the treatment of RAS wild-type metastatic colorectal cancer (mCRC). It was approved and launched in the U.S. in September 2006 and in Japan in 2010 as a monotherapy for patients with EGFR-expressing mCRC after disease progression following treatment with chemotherapy drugs including pyrimidine fluoride, oxaliplatin, and irinotecan.
The cornerstone of treatment for colorectal cancer is to completely remove the primary lesion (the tumor in the colon) and metastatic lesions (tumors in other locations) by surgery. However, if the tumor cannot be removed by surgery, or if the cancer recurs after surgery and the tumor cannot be removed, the disease is classified as “unresectable” colorectal cancer. This is not based on whether the tumor can technically be resected but whether the cancerous tissue can be completely removed and recurrence of the cancer can be controlled for a long period. If the cancer is judged to be unresectable, systemic chemotherapy is administered to control disease progression, prolong life and control cancer-related symptoms.
Takeda is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology. We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit https://www.takeda.com.
The drug information contained herein is intended to disclose corporate information. Nothing contained in this document should be considered a solicitation, promotion, or indication for any prescription drug, including those currently under development.