June 1, 2015 1:50 p.m. ET
CHICAGO—The National Cancer Institute is launching a major clinical trial in which it hopes to become a matchmaker between 1,000 advanced cancer patients and a growing new or existing drugs that target genetic mutations that are driving the growth of their tumors.
The study, called NCI-Match, marks an ambitious effort by the NCI to advance the emerging field of precision medicine and to help spur the development of new drugs that might be effective against cancer-causing mutations. At least 10 pharmaceutical companies will provide a total of more than 20 treatments to be tested all under the structure of a single study.
“This is the largest and most rigorous precision oncology trial that has ever been attempted,” said James Doroshow, deputy director of the NCI, in announcing the launch of the study Monday. Researchers will begin screening patients next month at some 2,400 sites around the U.S.
The announcement came at the annual meeting of the American Society of Clinical Oncology, which is launching a similar study called TEPUR, in which five pharmaceutical companies so far have agreed to provide a total of 13 molecularly targeted drugs already on the market. The intent is to determine “what happens to patients who have their tumors sequenced and are treated with a targeted drug” that isn’t specifically approved for their cancer, said Richard L. Schilsky, ASCO’s chief medical officer.
Together the studies reflect how growing understanding of cancer genetics and the ever-lowering cost of DNA sequencing is changing how patients are treated and how drugs are developed to treat the disease. Several leading academic centers and some community oncology practices offer genetic analysis of tumor DNA for many of their advanced cancer patients in hopes of pairing them with a promising treatment, but little is known about how this is affecting patients.
A key driver of the strategy is the fact that the same cancer-causing molecular traits are often found in a variety of tumor types, raising hope that a drug effective against the target in, say breast cancer, would be effective in a tumor originating in another organ. Indeed, Roche Holding AG’s breast cancer drug Herceptin, which targets a receptor called Her2, turned out to be effective—and was eventually approved—for gastric tumors that have high levels of Her2.
But the drug Zelboraf, which is especially effective against the skin cancer melanoma with a certain mutation in a gene called BRAF, turns out to have essentially no effect against colon cancer harboring the same mutation.
“It’s a much more complicated issue than most people would like to hear,” said Richard Pazdur, chief of oncology at the U.S. Food and Drug Administration and a supporter of the studies. “I would have some element of caution” toward assuming broad success in the approach.
Another issue is that genetically characterizing tumors breaks common cancers such as lung or breast into a dozen or more much rarer diseases. That poses a challenge to drug companies, who in recruiting for a single-drug trial could have to screen as many as 10,000 patients to find enough patients to test a drug against a rare mutation, researchers said. Screening patients for a trial involving 10 or 20 drugs instead is expected to be much more efficient and more quickly provide patients with access to potentially beneficial treatments.
The NCI-Match study will initially obtain fresh tumor biopsies from some 3,000 patients and perform DNA analysis in hopes of finding about 1,000 with genetic alterations that make them candidates for drugs that will be will be available for the study. Their results will be analyzed by a panel of experts, and patients will be assigned to treatments based on the mutations, not where their cancer is located.
Novartis AG, Pfizer Inc., AstraZeneca PLC, Verastem and Boehringer Ingelheim are providing for a study a total of 10 drugs either already on the market or under development. Other companies are lined up to provide additional medicines for the study.
Each arm of the study will enroll up to 35 patients and the effectiveness of the drugs will be determined based on tumor shrinkage and how long patients live before their disease worsens. Drugs that shrink tumors in at least 16% of patients will be viewed as promising while those with a response of less than 5% will be considered unsuccessful. Depending on funding, Dr. Doroshow said, enrollment will be expanded for treatments showing a strong signal of response.
Roche’s Genentech unit, AstraZeneca, Bristol-Myers Squibb Co., Eli Lilly & Co. and Pfizer are the first to agree to provide already approved drugs for the ASCO trial. Patients will be treated with a drug that matches their molecular profile.
The plan is to enroll eight patients for each DNA-drug match and halt enrollment if no patient responds and expand enrollment to up to 24 patients if at least once patient responds to the treatment.
“These are trials that are an acknowledgment that we are in the midst of the era of precision medicine,” said Sandra Horning, Roche’s chief medical officer and head of global product development. “It will be a great way to learn where targeted therapies might have utility that we don’t understand.”
Write to Ron Winslow at ron.winslow@wsj.com
CHICAGO—The National Cancer Institute is launching a major clinical trial in which it hopes to become a matchmaker between 1,000 advanced cancer patients and a growing new or existing drugs that target genetic mutations that are driving the growth of their tumors.
The study, called NCI-Match, marks an ambitious effort by the NCI to advance the emerging field of precision medicine and to help spur the development of new drugs that might be effective against cancer-causing mutations. At least 10 pharmaceutical companies will provide a total of more than 20 treatments to be tested all under the structure of a single study.
“This is the largest and most rigorous precision oncology trial that has ever been attempted,” said James Doroshow, deputy director of the NCI, in announcing the launch of the study Monday. Researchers will begin screening patients next month at some 2,400 sites around the U.S.
The announcement came at the annual meeting of the American Society of Clinical Oncology, which is launching a similar study called TEPUR, in which five pharmaceutical companies so far have agreed to provide a total of 13 molecularly targeted drugs already on the market. The intent is to determine “what happens to patients who have their tumors sequenced and are treated with a targeted drug” that isn’t specifically approved for their cancer, said Richard L. Schilsky, ASCO’s chief medical officer.
Together the studies reflect how growing understanding of cancer genetics and the ever-lowering cost of DNA sequencing is changing how patients are treated and how drugs are developed to treat the disease. Several leading academic centers and some community oncology practices offer genetic analysis of tumor DNA for many of their advanced cancer patients in hopes of pairing them with a promising treatment, but little is known about how this is affecting patients.
A key driver of the strategy is the fact that the same cancer-causing molecular traits are often found in a variety of tumor types, raising hope that a drug effective against the target in, say breast cancer, would be effective in a tumor originating in another organ. Indeed, Roche Holding AG’s breast cancer drug Herceptin, which targets a receptor called Her2, turned out to be effective—and was eventually approved—for gastric tumors that have high levels of Her2.
But the drug Zelboraf, which is especially effective against the skin cancer melanoma with a certain mutation in a gene called BRAF, turns out to have essentially no effect against colon cancer harboring the same mutation.
“It’s a much more complicated issue than most people would like to hear,” said Richard Pazdur, chief of oncology at the U.S. Food and Drug Administration and a supporter of the studies. “I would have some element of caution” toward assuming broad success in the approach.
Another issue is that genetically characterizing tumors breaks common cancers such as lung or breast into a dozen or more much rarer diseases. That poses a challenge to drug companies, who in recruiting for a single-drug trial could have to screen as many as 10,000 patients to find enough patients to test a drug against a rare mutation, researchers said. Screening patients for a trial involving 10 or 20 drugs instead is expected to be much more efficient and more quickly provide patients with access to potentially beneficial treatments.
The NCI-Match study will initially obtain fresh tumor biopsies from some 3,000 patients and perform DNA analysis in hopes of finding about 1,000 with genetic alterations that make them candidates for drugs that will be will be available for the study. Their results will be analyzed by a panel of experts, and patients will be assigned to treatments based on the mutations, not where their cancer is located.
Novartis AG, Pfizer Inc., AstraZeneca PLC, Verastem and Boehringer Ingelheim are providing for a study a total of 10 drugs either already on the market or under development. Other companies are lined up to provide additional medicines for the study.
Each arm of the study will enroll up to 35 patients and the effectiveness of the drugs will be determined based on tumor shrinkage and how long patients live before their disease worsens. Drugs that shrink tumors in at least 16% of patients will be viewed as promising while those with a response of less than 5% will be considered unsuccessful. Depending on funding, Dr. Doroshow said, enrollment will be expanded for treatments showing a strong signal of response.
Roche’s Genentech unit, AstraZeneca, Bristol-Myers Squibb Co., Eli Lilly & Co. and Pfizer are the first to agree to provide already approved drugs for the ASCO trial. Patients will be treated with a drug that matches their molecular profile.
The plan is to enroll eight patients for each DNA-drug match and halt enrollment if no patient responds and expand enrollment to up to 24 patients if at least once patient responds to the treatment.
“These are trials that are an acknowledgment that we are in the midst of the era of precision medicine,” said Sandra Horning, Roche’s chief medical officer and head of global product development. “It will be a great way to learn where targeted therapies might have utility that we don’t understand.”
Write to Ron Winslow at ron.winslow@wsj.com
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