乌鸦传媒

Patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) who were treated with zilovertamab (formerly cirmtuzumab) and ibrutinib (Imbruvica) in a phase I/II trial showed promising responses and tolerability of therapy, according to data presented at the .

In this exclusive 乌鸦传媒 video, lead study author of the Department of Lymphoma & Myeloma at the University of Texas MD Anderson Cancer Center in Houston, discusses .

Following is a transcript of his remarks:

So, as you all know, ROR1 has been a brand new target -- a novel target that has shown to be expressed in neoplastic cells. And its mechanism of action in terms of proliferation and metastases of malignant conditions has been very interesting for us because of its unique expression on these neoplastic cells.

We know that cirmtuzumab, or now zilovertamab, is a humanized monoclonal antibody that binds to ROR1, which does not allow for WNT5A signaling downstream, which inhibits the proliferation and the stemness of what we call neoplastic cells. And it seems to work very well complementary to the BCR signaling pathway. And that was the impetus for the study, where we can block both pathways and possibly be able to get rid of this minimal residual disease that can be commonly seen with the use of ibrutinib.

So this was a phase I/II study design for part one; we're finding the right dose. We were able to find the recommended phase II dosing of 600 mg three-biweekly dosing followed by monthly dosing Q4, and that was taken into MCL, CLL. And we'll also have an MCL marginal zone cohort that is also starting.

What we really wanted to highlight was the long-term efficacy data that has been just produced, the MCL progression-free survival. As you can see here on your left, zilovertamab plus ibrutinib on 27 valuable patients in mantle cell lymphoma, and you can see the medium progression-free survival of all comers, 36 months approximately, compared to the historical, the PCYC-1104, and the ... combination of 370 patients, which had a median progression-free survival of 12.8 months ... which appears favorable and promising for the combination of zilo plus ibrutinib.

And in terms of the efficacy by the number of lines, as you know, ibrutinib is very efficacious and especially used earlier in disease settings. You can see here in our zilo plus ibrutinib, it did not really matter, but due to small numbers, I agree. But whether it was one line of therapy, two lines of therapy, or greater than three lines of therapy, demonstrating there may be a promising signal for zilovertamab.

As you can see in the ibrutinib single agent, if you go down to one line, two lines, you can clearly see that the progression-free survival drops precipitously compared to the one line of therapy. And those with high-risk features such as the p53 mutations, as you can see here, those with no p53 mutations had an excellent response of a 100% PFS [progression-free survival] versus those with the p53 mutations. We have a median progression-free survival of about 17 months compared to the historical -- demonstrating a promising signal that this may be a combination that is worth pursuing further.

And this is the CLL group, as you can see in the landmark PFS compared to the single-agent historical data, it appears you can see here for those patients with one to two lines of therapy, there were at 100% PFS demonstrating promising signal. And for those with greater than two, they had 24 and 36 months of almost 90% and 70%, respectively, compared to the 50 to 60% that was seen with the historical data.

So these are all kind of very interesting data; you really can't direct-compare or cross-study, but you know, these are promising signals that we really feel that this is worthwhile. And especially with the setting of the toxicity data, which I did not show, but which was presented previously, we had very minimal changes in terms of the toxicity profile. It actually appeared better tolerated when you combine these two agents together -- the zilo plus the ibrutinib.

So this is very exciting data, and because of the the phase II data we're moving on with the phase III randomized study, and I think this will be very beneficial to many of our patients who would like to get additional efficacy benefit with minimal increase in toxicity.

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