Tests have confirmed that the level of TMB, a biomarker, has nothing to do with the patient's ultimate outcome!

in order to gain a place in the over-profitable non-small cell lung cancer market, some immuno-oncology companies have turned to studying biomarker tumor mutation load TMB. But the latest figures from lung cancer giant Mercedon show that the biomarker's effectiveness is questionable.At the World Lung Cancer Congress in Barcelona on Sunday, Mercadon presented the results of two exploratory analyses that concluded that tumor mutation load TMB did not seem to determine which patients benefited from the Keytruda plus chemotherapy combination.In his Phase 2 Keynote-021 study and its Phase 3 Keynote-189 study, Mercedon studied tumor mutation load TMB data from patients, both of which tested the immuno-oncology star therapy Keytruda combination chemotherapy to treat previously untreated patients with non-small cell lung cancer. In both trials, the combination showed consistent efficacy in patients with different tumor mutation load TMB levels, and Mercedon did not find a significant correlation between tumor mutation load TMB and the ability of the treatment combination to trigger a patient response, delay disease progression, or prolong survival.Dr. Roy Baynes, Senior Vice President and Head of Global Clinical Development at Mercedon, said, "The results of treatment have proven to be unaffected by tumor mutation load TMB status. Keynote-189 reinforces Keytruda's combined chemotherapy portfolio as a treatment for first-line lung cancer and is an important data set, and these new exploratory results will help provide considerable guidance to academic researchers and doctors who are very interested in tumor mutation load TMB. Afterimmunotherapy entered clinical practice, tumor mutation load TMB was a good predictive indicator after PD-L1 in recent years. TMB reflects the number of genetic mutations present in the tissues of tumor patients. The more genes mutated in tumor patients' tissues, the more likely they are to produce more abnormal proteins, and the more likely they are to be detected by the patient's immune system, thereby activating the patient's own anti-cancer immune response, so the better the ultimate outcome with external tumor immunotherapy.Baynes said the new findings are good news for Mercedon because they make it very clear that all patients who are able to withstand chemotherapy should be treated in combination with Keytruda. However, this trial data does not bode well for companies seeking to segment tumor mutation load TMB as a segment of the patient population. Even more unfortunately for companies, there was little evidence last year that tumor mutation load TMB had a significant impact on patients' ultimate outcomes.This is not the first time tumour mutation load TMB has suffered a setback. In its Checkmate-227 trial, Paxmouth found that opdivo combined with Yervoy to increase a patient's progression-free survival rate by more than three times (42.6% vs13.2%) in patients with tumor mutation load TMB of more than 10 mutations per Mb of non-small cell lung cancer. The trial is also the first prospective clinical study to confirm that tumor mutation load TMB can be used as a predictive marker of immunotherapy effectiveness.Based on the test results in Checkmate-227 that proved that Opdivo Yervoy was significantly superior to chemotherapy in its non-progressed lifetime, Shishi Shiguibao submitted a sBLA application. However, in March 2019, new data showed that patients with high or low TMB levels of tumor mutation load did not actually differ in the final survival results, and after discussions with the U.S. Food and Drug Administration, The Hundred Mercy had to withdraw the application.Baynes added that this does not mean that the role of tumor mutation load TMB in treatment options ends. "We continue to believe that tumor mutation load TMB is an important area of research, and Mercedon is doing the same research." (
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