There appears to be a discrepency between what is qouted in the results section of the abstract and what is found in the table summarising the results. The authors have stated that the best responses were 1 CR, 5 PR, and 4 stable diseases. However, the finalised table shows that of the 10 patients that showed a response to treatment, 4 withdrew from the study and 1 died shortly after their disease progressed and 2 died shortly after achieving a response. This indicates to me that 1 patient withdrew from the study with a partial response and another completed the study with a stable disease.
I am curious as to whether "best response" was a primary outcome measure for the HER-vaxx phase 1b clinical trial?
Another thing that stood out to me was that HER-vaxx was used in combination with three other FDA approved drugs, which consisted of cisplatin in all cases and either 5-fluorouracil or capecitabine. Also, the researchers of the trial were allowed to vary the dose and duration of the chemotherapy given to each patient as indicated. However, I cannot find a table or discussion that has summarised how much chemotherapy each patient recieved during the duration of the study. Without knowing the total dose of combination chemotherapy provided to participants, I imagine it would be difficult to infer how much effect HER-vaxx was having compared to how much effect the FDA approved chemotherapeutic agents were having.
I'm wondering if this information has been provided to you by IMU?
Lastly, I'm wondering if it is unusual for you to see so many grants being given to researchers throughout the duration of the study as well as after the study. I'm also interested that some of the people that took part in the study, which include C.C. Zielinski and U. Wiedermann (who also recieved grant money from Imugene), have patents issued for B cell epitopes of HER2/neu (2).
I am curious as to whether this provision of grants to researchers conducting the trial is customary for biopharmaceutical companies?
1
https://clincancerres.aacrjournals.org/content/early/2021/05/06/1078-0432.CCR-20-3742.full-text.pdf2
https://patents.google.com/patent/US20170119867A1/en?oq=US2017%2f0119867A1Phase II HER-vaxx interim results (3):I am wondering if I could get your thoughts on the interim results for the phase II HER-vaxx interim results. I have linked a screenshot from the announcement below. The current HR is 0.418 with an
80% confidence interval of 0.186 and 0.942, indicating that patients with HER-vaxx have an median 58% better chance of survival. However, had a 95% confidence interval been used, the result would not have been significant, as the upper bound would have crossed one. The standard for FDA approval is 95% confidence intervals, which, if used in this study, would indicate that the results seen in these interim results are not significant. By comparison, the study of herceptin that the announcement elluded to had a HR of 0.74 with a
95% CI of 0.61–0.91, indicating that herceptin + chemo has a 95% chance of showing benefit (4).
Have IMU disclosed whether or not they will be using a 95% confidence interval in their final results?
Since the 80% CI is so large (0.186, 0.942), this clearly indicates that some respond well to the HER-vaxx treatment (while others do not), so have IMU isolated the population subgroup characteristics that show increased efficacy to HER-vaxx?
Also, it appears that current studies are looking at combining HER-2 antibodies to provide a better effect (5). I've attached the results section and briefly state that it appears the inclusion of pertuzumab (HER-2 antibody) to combination trastuzumab and chemotherapy showed better efficacy than trastuzumab and chemotherapy (the control). This would indicate that combining the HER-2 monoclonal antibodies is showing even better efficacy than when used as a monotherapy. Also, it appearst the combination is quite well tolerated and safe, as participants most common side effect was neutropenia, anemia, and leukopenia - typical side effects of cancer therapy.
Given the shift to combination therapy with HER2 monoclonals, I'm wondering what peoples thoughts are on the marketability of HER-vaxx if successful in the P2 trial?
To replace the current standard of care monoclonals, I imagine Imugene would have to run an phase III trial in the US, which may take a few years and cost ~$100-200 million dollars to complete (6). Of course, going up against the current standard of care therapies confers a lot of clinical risk. Another alternative is that if HER-vaxx was not to replace current standard of care therapies, it would then have to be an adjuvant therapy. Fortunately, this science is progressing as well, with an adjuvant B cell technology being shown to be highly effective in combination with current standard of care therapies (7). Imugene would still need to run a phase III trial in the US to pursue this avenue. I imagine they would be getting together a feasability study and determining how they will pay for such a trial.
I am wondering if investors on this forum have evaluated the clinical risk of a P3 trial against established SOC drugs? If so, I would love to see your analysis.
Have IMU disclosed how they plan to proceed with HER-vaxx after they get their phase II trial results?
3
https://newswire.iguana2.com/af5f4d73c1a54a33/imu.asx/3A556044/IMU_Imugene_HER_Vaxx_shows_positive_Overall_Survival_in_trial
4
https://www.nature.com/articles/s41598-019-54402-9
5
https://pubmed.ncbi.nlm.nih.gov/31234927/
6
https://www.appliedclinicaltrialsonline.com/view/new-research-emerges-challenge-steep-costs-clinical-trials7
https://pubmed.ncbi.nlm.nih.gov/31978707/Phase I PD1 vax trial Since a minimum of three people are required for each dose increment (8), I am wondering if IMU have provided information on the third patient from cohort one (the lowest dose)? The screenshot was taken from the most recent dose increase update.
8
https://newswire.iguana2.com/af5f4d73c1a54a33/imu.asx/3A556936/IMU_Imugene_First_Patient_Dosed_in_PD1-VAXX_Clinical_TrialCF33 & CD19Lastly, after the recent purchase of CD19, I'm wondering if IMU have provided any legitimate reason as to why CF33 has not yet been succesful in its IND application?
It appears that there were licensing and manufacturing updates in 2019, with an IND submission/completion expected late 2020. So, I was wondering if investors had heard anything in relation to the results of the IND meeting of IMU and the FDA?
Since the success rate of novel compounds from the preclinical stage to FDA approval is a 1 in 250 chance (roughly 0.004%), I am wondering if IMU have disclosed why they have purchased another preclinical compound? I find it strange they would do such a thing while they have a phase II asset (HER-vaxx) and a phase I asset (PD1-vaxx) with much higher chances of FDA approval?
Also, considering that the global CART drug market value is expected to be around USD $3.1B by 2023 (9) and there are currently many FDA approved CART treatments available (10), I am wondering if anyone has evaluated risk for reward for their most recent purchase (CD19) as well as the oncolytic virus CF33?
9
https://www.businesswire.com/news/home/20200611005377/en/Global-CAR-T-Therapy-Market-Assessment-2020-2030---ResearchAndMarkets.com10
https://hillman.upmc.com/mario-lemieux-center/treatment/car-t-cell-therapy/fda-approved-therapiesIf you
@unbelievable or someone else could answer my questions directly, that would be appreciated.
(20min delay)