The GLOVe study was designed specifically to evaluate patients with what we deem high-risk mantle cell lymphoma. That term itself is a bit ambiguous because, again, there are a couple of different patient characteristics, disease and presenting clinically-wise that will highlight patients having high-risk disease. But for our trial we chose the inclusion criteria based on the JCO article by  Jain et al. that was published looking at criteria to segregate patients into high risk and ultra-high risk. So specifically in this study we were focussed on patients with blastoid and pleomorphic variant, elevated Ki67 ≥50%, elevated high risk by MIPI, complex cytogenetics or P53 mutations, 17p deletions.

Based on this we decided to incorporate a bispecific antibody, so a CD20/CD3 bispecific antibody. As of to date most clinical data supports the use of glofitamab and so that’s the bispecific we chose for the clinical trial. Then we decided to combine this with two oral medications, initially with venetoclax and then adding on lenalidomide.

From this patient population, again looking for patients who met these high-risk features, if you didn’t have these features you were not eligible for the study, and, again, looking for patients who had symptomatic mantle cell lymphoma, either clinically or lab based that required treatment intervention.

With our presentation we presented data on patient characteristics on 28 patients and response evaluable and treatment-emergent adverse events on 27 patients, based on the time the patients had been enrolled on the study. What we demonstrated in this clinical trial was that with a lead-in of venetoclax, starting with venetoclax at 50mg and escalating the dose weekly up to a dose of 200mg, we thereafter introduce obinutuzumab over two days per what is standard approval process for glofitamab pre-treatment. The following week, once we escalated to venetoclax 400mg, we started the glofitamab step-up dosing, going from 2.5mg to the following week 10mg, then 30mg. Once we reached the 30mg dose the glofitamab was thereafter given every three weeks and continuing with the venetoclax 400mg.

In the initial protocol on cycles 3-8, which was after we reached the 30mg dose of glofitamab and venetoclax was at the 400mg dose, we did add lenalidomide, either 10mg or 20mg based on the patient’s creatinine clearance. Thereafter patients would thereafter continue these medications, this triplet, for a total of 12 cycles, each cycle being 21 days. After they complete 12 cycles patients who were in complete metabolic response were thereafter allowed to go into maintenance therapy where they would continue the venetoclax for four months, the lenalidomide for six months and then the glofitamab was given every other month for approximately two years.

What we were able to demonstrate in this clinical study as far as results is that we found a high rate of complete metabolic response at the first response assessment, which was at nine weeks. Concurrently we saw a very high rate of undetectable MRD analysis at 10-6 at this nine-week assessment. Based on this and based on some of the data we saw as far as toxicity, specifically GI toxicities and neutropenia, a lot of which we attributed to the inclusion of lenalidomide, we subsequently made some changes within the later protocol to then try to improve patients’ tolerance. As of the ASH presentation, we had not noticed any patient progressions on treatment i.e. no patients who were evaluable for response had lost that response. We had not had any patients lapse molecularly either so there was no positive change in the MRD assessment at the time of data cut before the ASH presentation.

So, given the median follow-up for this presentation was only 10 months we still do need more follow-up on the study to determine the true durability of this regimen in this high-risk and difficult to treat patient population. But at this early timepoint the results appear very encouraging.

Now, the goal at this point is to completely enrol the study so we do have a total of 22 more patients that need to be enrolled into the clinical protocol before we complete enrolment. So we are still actively working to complete this. Then we will hope to have a more mature and updated response assessment and evaluation of treatment emergent adverse events in the next 1-2 years after we can complete study enrolment.

As I mentioned, due to some toxicity issues we have adjusted the protocol so patients will only get lenalidomide now if they do not necessarily obtain a complete metabolic response or an undetectable minimal residual disease test after cycle 6, which is approximately 18 weeks of treatment. Patients who still have metabolic active disease or a positive MRD test will thereafter add the lenalidomide at that point which they will continue through cycle 12 and then again for the six months of maintenance.

So very optimistic about the protocol and we hope to continue to be able to report positive results from this at a future study meeting.