What we were studying here is the bispecific antibody mosunetuzumab which is a bispecific antibody that targets CD20 on B-cells and CD3 on T-cells. Mosunetuzumab in the US has been approved by the FDA for treatment of patients with follicular lymphoma that has relapsed after at least two prior therapies. The approved route of administration is intravenous. There is a subcutaneous formulation of mosunetuzumab that is approved in Europe but is not yet approved in the US. So we studied the subcutaneous formulation in this trial, MorningSun. What MorningSun was all about was testing this formulation in scenarios in which mosunetuzumab had not previously been tested, so specifically it was a so-called basket study looking at mosunetuzumab in treatment naïve patients with follicular lymphoma, both high and low tumour burden, and also in elderly patients with DLBCL who are unfit for conventional therapy, relapsed mantle cell lymphoma, transformed lymphoma and Richter. So it was a big basket study.
What I presented on at this meeting was the cohort of patients with high tumour burden follicular lymphoma. So that was the purpose of this cohort that we were studying here.
What was the study design?
It was a phase II trial and eligible patients had high tumour burden follicular lymphoma for this cohort. The primary endpoint of this cohort was rate of progression free survival at two years. What I reported on was follow-up a little bit short of that; we have an 18 month estimation of the progression-free survival. All patients received, as I said, subcutaneous mosunetuzumab on the dose and schedule that’s been used in other studies of subcutaneous mosunetuzumab, namely they got a 5mg dose on cycle 1, day 1, and then a 45mg dose on cycle 1, day 8, another 45mg dose on day 15. It’s a 21-day cycle so then they got a 45mg dose on day 1 of cycles, 2 through 17. So the goal was to treat patients for 17 cycles, which is basically one year of treatment. Then there was an option for patients who at the end of their year were in at least a partial remission to continue maintenance mosunetuzumab for a year with a dosing schedule in the maintenance phase being one dose every eight weeks for a year. So basically six doses separated by eight weeks each. So that was the design of the study.
What were the key results?
We enrolled just over 100 patients, 103 patients, and all of them had a high tumour burden. The progression free survival, we have estimates up to 18 months, was 85% estimate at 18 months and we have an estimation for overall survival at 18 months of 92%. The overall response rate was 88% and the rate of complete metabolic response by Lugano criteria was 65%. The mosunetuzumab appears to have activity in all subgroups, including high risk subgroups.
In terms of safety, the most common toxicities were injection reactions which happened in about two thirds of patients, fatigue and cytokine release syndrome, which occurred in about a third of patients. We went into some detail in the presentation on the infections, they were mostly upper respiratory tract. The majority were low grade 1 and 2 and resolved with treatment. There were three grade 5 infections, two of which were COVID and one of which was a pseudomonas pneumonia.
The other comments were about cytokine release syndrome, which was essentially all grade 1 and 2. There were nine patients who required tocilizumab but the CRS was manageable, all the patients were able to be treated as an outpatient. There was no mandatory hospitalisation here. There were some patients who got hospitalised if they developed CRS or other complications but they were reactive hospitalisations in this trial.
The other thing I reported in terms of efficacy is this is the first look we’ve had at results of circulating tumour DNA levels. We measured those only in patients who achieved a complete metabolic remission. We measured them at cycle 4 day 1 and cycle 8 day 1. We had measurements available for 38 patients although more patients achieved complete metabolic remission so we’re going to present and gather additional information on additional patients once we have that. But in these first 38 patients that we had data on, 84% of them had undetectable ctDNA at cycle 4 day 1 and the rate at cycle 8 day 1 was about the same. There were just a few converters from positive to negative or negative to positive between the two. There haven’t been enough progression events so far for us to tell whether positivity for ctDNA was predictive of early relapse so more to come on that at a future analysis.
So our conclusion was that mosunetuzumab has good activity in patients with high tumour burden follicular lymphoma and, as measured by ctDNA, the responses appear to be deep and relatively rapid with 84% being undetectable by cycle 4 day 1. The treatment is relatively safe and deliverable in the outpatient environment in community practices like mine. So those were our primary conclusions.
