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 The company has been analyzing biomarkers in 300 patients from its
Imvigour 210 bladder cancer study to learn more about those who did
not respond to its Tecentriq treatment, it said at the European
Society for Medical Oncology meeting in Geneva.
Its doctors now believe some tumors that express high levels of a
protein called TGF-beta develop a fortified wall. T-cells stick as
if to "Velcro," the adhesive hook and loop fastener common on
clothing, and fail to get inside, they said.
Using a mouse model, they described how they then combined anti-TGF-beta
agents with Tecentriq to help keep T cells from getting hung up.
"T cells penetrated into the center of the tumor, and the tumor
reduced in size," said Sanjeev Mariathasan, a senior scientist at
Roche's Genentech unit in San Francisco.
Mariathasan said cancers including lung, pancreatic and colorectal
exhibit similar T-cell resistant traits, so such a combination could
be tested in those, as well.
Tecentriq, approved for bladder cancer and second-line lung cancer
treatment, is a key part of Roche Chief Executive Severin Schwan's
plans to replace waning sales of older drugs with new medicines.
On Thursday, Roche released data showing Tecentriq added to older
drugs doubled the percentage of lung cancer patients who survived a
year without disease progression, part of efforts to expand
approvals to earlier treatment.
But while so-called "checkpoint inhibitors" like Tecentriq, Keytruda
from Merck and Opdivo from Bristol-Myers Squibb have produced
durable responses in some cancer sufferers, they are only effective
in a fraction of patients.
Consequently, researchers are feverishly seeking to understand why
they fail in 70-80 percent of the time.
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"It is key to identify the factors that impede more generalized
benefit," said Ignacio Melero, a professor at the Centre for Applied
Medical Research (CIMA) in Pamplona, Spain, who reviewed Roche's
analysis.
He said its insights offer a potential new approach in helping the
immune system fight cancer.
"Perhaps we can identify, by means of gene signatures, a fraction of
patients in whom TGF-beta is the dominant mechanism and focus on
synergistic combinations" to help overcome disease resistance, he
said.
BETTER AGENTS NEEDED
Even so, Melero said much work remains given that anti-TGF-beta
agents have so far stumbled on efficacy or safety concerns, despite
years of study for their potential in cancer therapy.
"Better anti-TGF-beta agents need to be developed for use in
combination with immunotherapy agents," he said.
(Reporting by John Miller; Editing by Subhranshu Sahu)
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