Transcript: The OptiTROP-Lung04 trial
Li Zhang, MD
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
- Sac-TMT, which is the sacituzumab tirumotecan, is the TROP2 ADC, with their novel linker and novel topo-1 inhibitor payload. So as we know, TROP2 is the over, highly expressed EGFR-mutant non-small cell lung cancer, and our previous studies that have been showing that the EGFR mutation can enhance the, the internalisation and the uptake of these drugs. And also the phase one, phase two studies that already showing the highly efficacy in this population compared with wild-type population. For EGFR-mutant non-small cell lung cancer, as we know third EGFR-TKI as a first-line treatment. However, all the patients that were eventually developed resistance. We already have some combination treatment which is combined with chemotherapy, with immunotherapy, antiangiogenic agents or EGFR c-MET antibodies, and also HER3 ADC.
However, all these studies do not show any over survival benefit. So this is the background of our study design. So the OptiTROP-Lung04 study is a randomised phase three open-label studies and all the patients that was randomised, which is their EGFR-mutant non-small cell lung cancer patients who progressed on the EGFR-TKI, and then patient was randomised to receive the platinum-based chemotherapy or the sac-TMT. So this is the studies trying to showing whether the sac-TMT is can achieve the better result compared with the standard platinum-based chemotherapy. So this is the rationale and the design of the study. This is a randomised phase three studies. Totally we have 376 patients was randomised and patients was randomised to receive the sac-TMT versus the standard platinum-based chemotherapy. And the primary endpoint was the PFS by BIRC, assessed by BIRC, and also the second endpoint was OS, OR-PFS by investigator, and also the objective response rate and also the safety.
So, the data cut off we have progress, PFS by BIRC was 8.3 months in the study arm and 4.3 months in the control arms. The hazard ratio was 0.49 and P-value was less than 0.0001. Highly significant. And the one year PFS rate was 32% in the study arm and 7.9 months in the control arms. And also subgroup analysis also showing all predefined subgroup patients that was benefited from sac-TMT. And the interim analysis, the sac-TMT arms the medium PFS in sac-TMT was not reached and they are in chemotherapy, it's 17.4 months. The hazard ratio was 0.60. P-value less than 0.001. Also highly significant. And also the sac-TMT significantly improved over survival over chemotherapy, with 40% lower risk of death. And also subgroup analysis showing all the patients that, all the subgroup patients was benefited from the sac-TMT arms. So this is the main study result. And then moving to safety. The median duration of treatment is longer in sac-TMT arms compared to chemotherapy, 9.6 months versus the 4.9 months. And also the instance of the TRAE and grade 3 and above TRAE was similar in the two groups, and serious TRAE was less frequently occurs in the sac-TMT group. And the most common TRAE in both arms are haematological. Anaemia, neutropenia, and thrombocytopenia.
So the sac-TMT associated with a higher instance of dermatitis. Most cases was grade 1 and grade 2 and manageable. And ILD toxicity, which is also common in TROP2-ADC drugs, it occurs 9.6% in the study arms and also grade 1 and grade 2. So there was no IOD in the, ILD or pneumonitis that was reported in sac-TMT arms. So this is the overall view of the study result. Given this study result, you know sac-TMT demonstrate a statistical significant and clinical meaningful improvement in PFS and OS compared to platinum chemotherapy and also with safety manageable profiles in sac-TMT arms. and also with safety manageable profiles in sac-TMT arms. We think this sac-TMT will provide a promising new treatment option for patients with EGFR-mutant non-small cell lung cancer who progressed on EGFR-TKI. Actually this indication already approved by Chinese FDA.
So which is available our, actually practise changing for our patient's treatment. So for the subgroup analysis, so in terms of, I think it's the, the right now it's the, in our studies that we, the inclusion criteria is to ask all patients with brain metastasis had been treated. In other words, no treated patients were not allowed enrollment in these studies. This is the, I think it's the further, to explore whether the brain metastasis no treatment populations will, can benefit from these studies. We cannot answer this question because we do not allow the brain metastasis, no treatment include in these studies. This is the main, I think is the subgroups. I cannot answer this questions. These questions will be answered by the global, the similar style design in the, this drug is already ongoing global studies that monotherapy versus the platinum-based chemotherapy, in the global studies that, and I think that they will be answered these questions.
The global study, I think that is still on active enrollment. I think they are almost 70 to 80% patients that will finish the enrollment. We have another, a small part of patients that are still waiting for the finished. So I think it's the, at the end of next year, I hope we will be have a final result of the global trials and well, I think, I personally think there will be another positive trials. I also think that this drug will benefit not only Chinese population but also the outside China.
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