Transcript

Hello. My name is Michael Dickinson. I'm a hematologist and the disease group lead in aggressive lymphoma at Peter MacCallum Cancer Centre and Royal Melbourne Hospital in Melbourne, Australia. It was my pleasure, at EHA, to present an update on the results of a clinical trial of a drug called glofitamab.

Glofitamab is a novel 2-to-1 format, bispecific, T-cell-engaging antibody. It has 2 CD20-binding molecules and 1 CD3-binding molecule. This gives it special properties and, apparently, higher potency in experimental conditions comparing it to other CD20/CD3-binding agents.

We presented the results of a phase 1 clinical trial that has now been running for quite some time. The key inclusion for this clinical trial were patients with relapsed and refractory B-cell lymphomas, at least 1 prior therapy, and with an ECOG performance status of up to 1.

We treated patients at doses escalating from as low as 5 micrograms all the way up to 25 milligrams. Recruitment began in single-patient cohorts and then expanded into multi-patient cohorts triggered by mild safety events. The study has now moved into an expansion clinical trial.

I was able to present the results of the dose escalation phase of the study. What was striking about the patients that we recruited was that this was a population of patients with aggressive lymphomas and highly refractory, heavily treated disease.

We reported patients who'd been treated at 600 micrograms and above, which was the active dose and also subdivided patients into those treated at 10 milligrams and above, which was what we thought to be the optimal dose.

Approximately 80% of patients in the clinical trial had aggressive histologies, predominantly diffuse large B-cell lymphoma and transformed lymphoma. We had a few cases of Richter's syndrome, mantle cell lymphoma, primary mediastinal B-cell lymphoma. All of the indolent lymphoma patients that we recruited had follicular lymphoma.

What we saw from the clinical trial was that glofitamab induced a very high complete remission rate in this heavily pre-treated patient population. Patients with diffuse large B-cell lymphoma had received at least 3 prior lines of therapy as a median.

We saw complete remission occurring in 34.1% of patients with aggressive histologies treated at 10 milligrams and above and in 50% of patients treated with indolent histologies.

For the first time, now, with this longer follow-up, we're beginning to see what I consider to be a very clinically significant finding, which is that in patients who achieved these complete remissions, they're generally retained.

We saw that the median duration of complete remission has not been reached after a median follow-up of 10.2 months and that we have a significant number of patients who retained their complete remission beyond 12. Indeed, I've seen patients beyond 24 months in ongoing complete remission following treatment.

There were some safety signals which are linked to the mechanism of action of glofitamab. We did see cytokine release syndrome. This typically occurred after the first cycle of treatment, was typically Grade 1 or Grade 2, and was typically manageable.

We saw some neutropenia, which was reversible with G-CSF and which did not lead to infection or treatment discontinuation. Indeed, the incidence of adverse events that led to treatment discontinuation was as low as 3.2%.

About half of patients had serious adverse events, but these were predominantly precautionary rehospitalizations, as per protocol, to observe patients who experienced a mild fever.

This is an agent where we are looking at it with respect to how it performs compared to what is already available for patients out there. With that in mind, we were very conscious of the potential presence or absence of neurotoxicity akin to what is seen with CAR T-cells.

Here, the rates of neurotoxicity were determined using the CTCAE guideline, we did not use the ICANS measures of assessments or ICE tools, but we found the rate of neurotoxicity that was like he immune-cyto effector cell syndrome to be extremely low and in that sense, differentiating this product and making it deliverable to this patients population in need.

This clinical trial continues to recruit to the expansion cohort. There are several different expansion cohorts here. One of the things that separates this bispecific agent from other bispecific agents is evidence in the pre-clinical and now clinical setting that it retains its potency even in the presence of other CD20 antibodies, such as obinutuzumab or rituximab.

Various combinations are now being tested in ongoing clinical trials. We have seen from this clinical trial that this drug retains potency after pre-treatment with obinutuzumab, which we used as a way of ameliorating cytokine release syndrome.