As we know, Sac-TMT is the TROP2 ADC with a biofunctional linker and the novel [??] inhibitor. So TROP2 is overexpressed in EGFR mutant non-small cell lung cancer so we have preclinical studies that show that if the patient’s cancer cells have EGFR mutation and not only overexpression of the TROP2 but there is very high internalisation of the TROP2 Sac-TMT which increases curing the tumour cells. For EGFR TKI resistant cells the uptake is even higher than the EGFR TKI naïve cancer cells.
So we know that EGFR mutant non-small cell lung cancer the standard of care is TKI but eventually all the patients go on to develop TKI resistance. The standard of care is platinum-based chemotherapy, however, the PFS is around roughly 4 months so it’s a big unmet medical need.
Recently we have a lot of combination therapies which also achieve a PFS improvement, however, the overall survival is not statistically significant. So that’s why we designed the OptiTROP-Lung04 study. The OptiTROP-Lung04 study is a randomised open-label phase III study for patients with EGFR mutant non-small cell lung cancer developed from TKI resistance and randomised to receive Sac-TMT versus standard platinum-based chemotherapy.
The primary endpoint of the study was PFS but the key secondary endpoint was the overall survival and other parameters including ORR, TCR and safety. So this is the design of the study.
What results were you presenting?
The primary endpoint was PFS by BICR. We have a PFS in the study arm of 8.3 months versus 4.3 months in the control arm. The hazard ratio was 0.49 and the p-value was very significant, which is less than 0.001. In other words, we have at least 51% decrease for disease progression or death.
For the key secondary endpoint, which is the overall survival, the overall survival right now is the interim analysis result. At the interim analysis the study arm was not reached but in the chemotherapy arm, which is the control arm, the overall survival is 17.4 months and the hazard ratio was 0.60 and also a p-value less than 0.001. In other words, which is PFS positive and OS positive.
What was the safety profile?
Efficacy definitely is a winner for Sac-TMT but the safety is also very good. The TRAEs were similar between the two arms and serious TRAEs less in the Sac-TMT arm. The most side effect for Sac-TMT is mucositis which is very common for TROP2 ADCs but is always grade 1 and grade 2 and manageable.
The last point I want to add is the quality of life of this study. In this study we collected patient-reported outcomes of the quality of life questionnaires and you can see after three months the quality of life curves separating. The symptom deterioration is longer in the Sac-TMT groups than the chemotherapy arm. In other words, patients preferred Sac-TMT compared to chemotherapy. I think this is very important because patients feel much better than on chemotherapy. And that is the last point I want to add.
What are the implications of these results?
The impact is that last week the indication was already approved by the Chinese FDA so similar studies are very important for other countries’ colleagues in a similar design are ongoing. So hopefully in the next year or the year after next year, we will have global same study design results to show whether this compound will be helpful for other countries’ patients.
What is the take home message?
The take home message is that EGFR TKI is the standard of care for the EGFR mutant non-small cell lung cancer patients and resistance is eventually developed. The OptiTROP-Lung04 study is showing us that Sac-TMT is better than chemotherapy in terms of the PFS and OS and also safety.
