Would love to hear from anyone who is participating in / has considered and/or has knowledge of the NCT trial 04277637 - the Non-Randomized, Open-Label trial investigating the novel BCL-2 inhibitor BGB-11417?
I am approaching my first treatment for CLL and my CLL specialist is a PI in this study. We had discussed it a few months ago when the option was for Zanubrutinib and BGB-11417. However, now they have opened an additional arm that includes Obinutuzumab (with or without Zanu) on a time limited schedule.
This is a PHASE 1 trial and is also investigating the dosing...So I have some trepidation over those factors alone, but from what I have read, BGB-11417 is more selective for BCL-2, has less side effects and is extremely effective.
Would very much appreciate any insight. Thank you!!!
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Chi-town_Girl
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TY! Yes! This is an international trial- which is fantastic. I am gathering as much research and "real life experience" as possible so I can make the best informed decision. Appreciate the link and response. If I proceed with the trial, I promise to circle back here with my experience/outcomes. 😀
hi, I am in favour of trials but I would exercise some caution here.
My personal view is that I would not go into a phase 1 dosing trial for my first treatment. There are so many proven and very effective non chemo options now and I would opt for one of those. Obviously this depends on your country so if this is the only way of getting a non chemo option the I would do it.
Hi chi-town girl, I just signed the consent to participate in this exact trial, same arm as you at nwm chi. I was a little apprehensive about participating in a phase 1 trial, but this arm 5 is at the end of this trial so dosing appears to be already established and we know all about Obinutuzumab. BGB is a better version of Venetoclax. Dr Ma mentioned that someone else was considering participating in this arm. I start all of my pretesting in a week or so...
I'll start by saying I am very, very pro-clinical trial. However, I am not sure a "standard" CLL patient approaching their first treatment is best served by a Phase 1 trial. We don't know if the drug in a Phase 1 even works in vivo, but more importantly (to me) is we really don't know the potential side effect profile. There are a number of effective targeted medications available, and IMO a Phase 3 trial, which would help determine if one of our approved regimens is better than another, is a more conservative choice. You know it is likely to be effective, the question is, is one better than another. I say this as someone who has done a few Phase 1 trials, when I felt I had no other option except extremely high risk ones, or I was in a place where a delay in getting my CLL under control wouldn't be life threatening. I happen to have a difficult variant to treat, and so the risk of unknown side effects, to me, was worth it if I could get my critter under control.
One can make an argument that a patient with a mild disease, previously untreated, won't be adversely affected if the drug fails. And I think that argument is true. However, I personally am leery of being a guinea pig for something unless I have few other options. It's "supposed" to have fewer side effects, it may or may not actually turn out that way. The preliminary data (from non-CLL patients) involved only 51 patients. So enough to perhaps rule out overt, severe toxicity, but as far as the actual incidence of SE's? And what they are? No one can say just yet.
Studies using it for other cancers may support the "fewer side effects" claim, but haven't been published yet so we don't know the actual incidence. The researchers involved may be aware of fewer side effects, and talking amongst themselves/at meetings, but the percentages aren't yet published.
I do not see what number of patients were involved in the preliminary data release, so I can't comment on the statistical probability of any SE profile staying the same.
I do like that that in this study, it seems the CLL cohort will get dose escalation within their arm. To me, this means as long as I am not having side effects, the dose will be titrated up, with less time spent at a low dose that may not work. My previous Phase 1 trials didn't do this, and I was left to "fail" the drug after an initial period of the drug helping, instead of increasing it to see if it would continue working at a higher level. So I find this aspect of this trial very attractive. As well as, the treatment naive CLL folk *are* getting other, proven treatment. One gets zanibrutinib, obinituzumab, or both. So this is another point in favor compared to some Phase 1 trials IMO.
Please know the biggest warning takeaway for me, is that at some point, you *will* get some sort of side effect. The study is designed to determine the highest dose one can get before unacceptable side effects, which means the dose will be increased at some point, and not held or pulled back, until you do (if you do). If I were looking at treatment right now, I would be considering this trial. But since they are looking to establish the RP2D for this drug, people are going to be dosed up slowly until a SE occurs. This is how one establishes the dose of a drug in cancer trials, and the number of patients will necessarily be smaller than standard disease drug trials.
I have not been on this excellent site for a while, but now I would like to offer you some positive feedback and encouragement from my own experience.
I am on the BGB-11417 trial at Concord Hospital in Sydney. I was one of the first to start when Part 4 of the trial was approved for recruitment at the beginning of November 2021. I think I was actually the first of the treatment naive CLL/SLL patients to be screened (Cohort4B).
You might already be familiar with the overall study design. If not have a look at:
The study protocol I was under involved 12 weeks on Zanubrutinib mono followed by combination with BGB-11417. The start-up on the BGB-11417 was quite intensive with an 8 week ramp-up to target dose (TD), during which time there were lots of blood tests to monitor the effects. Depending on your blood counts and CT scan assessment of the size of your lymph nodes and spleen before the start on 11417 you will be assessed as low / medium / or high risk for TLS and that will determine whether or not you need to be on a drip during the day of the weekly ramp-up.
It is understandable to be a bit nervous about starting on a Phase 1 trial. I was not nervous about the Zanubrutinib as it is tried and tested, but I was a bit nervous about the BGB-11417, particularly when they doubled the target dose from the 80mg I was expecting to 160mg. I was overdue to start treatment with ALC around 300 and significantly enlarged spleen and lymph nodes so I was actually really looking forward to start the Zanu mono part.
The Zanu worked so well for me that I passed from high risk to low risk for TLS by the time of starting the BGB-11417, and thus did not need to be kept in on a drip. I was really happy about that !
The BGB-11417 worked so well for me that already by the end of ramp-up week 5 (on 20mg) my ALC was down to 3.6 and thus within normal range. My ALC reduction relative to baseline was actually better than any of the 7 CLL patients pictured in the ASH paper Combination chart.
Once through the ramp-up, the intensity of clinic visits becomes much less. After TD week 4 they go on to every 4 weeks, and after TD week 24 they go on to only every 12 weeks.
My CT scan after 24 weeks on target dose showed significant reduction in size of lymph nodes throughout and my spleen back to normal size. A blood test for MRD (Minimal Residual Disease) taken at the same time indicated MRD just above the iwCLL guidelines of 0.01% of leucocytes (in fact 0.011%). I was also feeling so much better and had been able to go back to my previous exercise routines some time before that.
To confirm CR – Complete Response requires a bone marrow examination. I submitted to that a couple of weeks ago in what was my TD week 52, that is after a year on target dose of BGB-11417. I have just received the results : COMPLETE RESPONSE.
On the issue of side-effects, I have had only a few temporary and quite tolerable side-effects.
My conclusion : These are great and extremely effective drugs and we are lucky to be been able to access them on this trial.
Kirsten, what a great result for you! Thanks for sharing your experience so comprehensively.
With respect to the ASH/Beigenemedical and clinical trials links, you'll need to copy the links, not the text displayed for the links, for the links to work. You can edit your reply via the 'More... Edit option under your reply. It can be tricky, so let me know if you need help. Having a competing BCL-2 drug is a huge deal, particularly if those who have CLL resistant to venetoclax can switch to BGB-11417.
Thank you for your kind comments and advice. I have just edited my post, inserting the links and adding the results of my blood test for MRD.
I so hope that targeted molecular drugs will soon be available as first line treatment for all CLL patients in Australia (and not only for those who have relapsed or been refractory to at least one prior therapy - usually FCR chemo). I noted that UK NICE has very recently approved Ibrutinib + Venetoclax for all CLL patients as their first treatment.
I contributed to the Leukaemia Foundation submission to the Pharmaceutical Benefits Advisory Committee (PBAC) looking at new drugs and improving access to existing ones through the Pharmaceutical Benefits Scheme (PBS).
BCL-2 with BTKi drug combinations are very good but the addition of Obinutuzumab holds a promise of being in a different league. Some trials are reporting results for triple drug therapies on par with continuous BTKi monotherapy.
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