This is probably the most appropriate thread to make my initial comments about the recent promising news about HER-Vaxx. It's been awhile since I've posted on HotCopper and it's nice to be back. I've held for Imugene for slightly over 4 years now and didn't really monitor the fluctuations until the share price jumped recently. Previously I held Viralytics (VLA) given my keen interest in the clinical research side. I'm not a statistician by trade but my honours degree did involve a survival analysis which designated the event as death (though it's been awhile!). Would like to offer my 2 cents on the recent results though I'm no expert. As usual, do your own research.
I'm absolutely thrilled about the preliminary results and cautiously optimistic. The seemingly superior overall survival (OS) of 14.2 months (HER-Vaxx + chemotherapy) versus 8.8 months (chemotherapy) is based on a very limited sample and that needs to be taken in to account. The alpha level was set at 0.10 which is rather lenient to determine whether the hazard ratio (HR) is statistically significant. Generally, the alpha level is set at 0.05 as the threshold - I might be lacking the statistical knowledge as to why the 0.10 was used. Thus, the p value reported by Imugene (i.e. 0.083) was considered as statistically significant, i.e. the result is likely not to have occurred due to chance. To be fair, this is a Phase 2 study for which the statistical power would be much lower than the ToGA Phase 3 study (Bang et al., 2010) which involved 594 patients. I'm really eager hearing how the HR will change when we reach the expected overall number of patients of ~34.
For those that are interested in the Phase 3 study that the announcement made reference to it - it's "Trastuzumab in combination with chemotherapy versuschemotherapy alone for treatment of HER2-positiveadvanced gastric or gastro-oesophageal junction cancer(ToGA): a phase 3, open-label, randomised controlled trial". Indeed the HR are relatively similar between the studies, i.e. HER-Vaxx combination therapy = 14.2 months; ToGA Phase 3 study combination therapy = 13.8 months. The challenge for Imugene and us will be for the Phase 2 study at the final analysis phase to produce the same survival benefit or even better. There is also the question of overall tumour response rate which I don't recall HER-Vaxx Phase 2 including as either a primary or secondary endpoint. A continued survival benefit with an increased sample size, however, should be a strong signal to the market about the legitimacy of HER-Vaxx even when compared to Phase 3 studies. I have the research article and have provided the survival curve for anyone who's interested.
There's some further evidence that increasing the dose of trastuzumab (Herceptin) doesn't lead to an significant increase in OS for patients with metastatic gastric or gastroesophageal junction adenocarcinoma (Shah et al., 2017). Do we know whether dosage could positively increase survival for HER-Vaxx? Maybe, maybe not? I really hope that it does. Lastly, and perhaps not exactly comparable, another Phase 3 study was recently published in September 2020 demonstrated pembrolizumab (Keytruda; an absolutely heavily researched and commercially successfully cancer drug) or pembrolizumab plus chemotherapy was not superior to chemotherapy for overall survival (Shitara et al, 2020). Survival curve added below as well. These studies, however, all differ in study design and patient recruitment and so are not completely comparable to the HER-Vaxx study. So please take these as very loose comparisons.
What is clear is that this cohort of patients (gastric cancer) need novel and effective treatments - the survival curves below tell a dismay story already. It's an incredible time for Imugene and we'll need patience and allow for the data to emerge. My fingers are crossed for the next six months and to see the final results for HER-Vaxx which hopefully the OS and HR will hold strong.
Apologies for the essay! I do love research and would love to hear anyone else's thoughts and perspectives on this. Good luck to us all and for the sake of these patients.
Trastuzumab in combination with chemotherapy versuschemotherapy alone for treatment of HER2-positiveadvanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial
Source: Bang et al., 2010 Efficacy and Safety of Pembrolizumab or PembrolizumabPlus Chemotherapy vs Chemotherapy Alone for PatientsWith First-line, Advanced Gastric Cancer; The KEYNOTE-062 Phase 3 Randomized Clinical Trial
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