LUMINICE is actually a study in relapsed/refractory classical Hodgkin lymphoma. This study actually explores, though… this study had two parts, one part was the run-in phase where we enrolled 24 patients in four different cohorts. In that we had two different dose levels for acimtamig, which is a bispecific antibody, with AlloNK, which is allogenic off-the-shelf unmodified NK cells. We had two different doses of those NK cells with the interleukin combination.

So the run-in phase explored four different cohorts and the ultimate goal was to have two of them dosage selected and randomised against each other in a stage 2 portion. We presented data of the run-in phase at EHA.

What was the study design?

The study design was actually a phase II but, as I was mentioning, there is a run-in phase in which we are exploring four different cohorts, two dose levels of the acimtamig as well as AlloNK. The study enrolled patients who had relapsed or refractory classical Hodgkin lymphoma. Out of those 24 patients most of them, nearly all of them, were exposed to brentuximab vedotin as well as a PD-1 inhibitor. All of them were refractory to PD-1 inhibitor, the majority of them were also refractory to brentuximab vedotin. All of these patients also received in the past multiagent chemotherapy.

Essentially these patients had very limited treatment options coming on the study. Acimtamig already has prior data as a single agent with a modest response rate which was published years and years back. At that time the theory was that as it is a bispecific antibody targeting CD30 as well as CD16a which is expressed in the NK cells, the patients who had been treated with multi-agent chemotherapy may not have optimal function of the NK cells. Therefore the study was designed based on a phase I study which was also published combining acimtamig with AlloNK. So that was the basis. These patients were quite relapsed/refractory to standard of care chemotherapy as well as brentuximab vedotin and PD-1 and these patients had very limited treatment options coming on the study.

What were the results of this study?

The primary endpoint of the study was overall response rate as well as safety and tolerability. We explored that this combination was safe and there were patients with infusion-related reactions as well as CRS. There was one grade 3 CRS event but that patient also had cytomegalovirus infection so there was quite a big overlap, but most of the patients had grade 1 or 2 CRS which was managed with the standard of care supportive care.

Overall response rate with this combination was 88% and a complete response rate of 58% which is very impressive in these relapsed/refractory classical Hodgkin lymphoma patients. Also the estimate of 6-month progression free survival was 61%. So imagine that these patients were relapsed and refractory to standard of care chemotherapy as well as CD30-directed brentuximab vedotin as well as PD-1 inhibitor, they had very limited treatment options. Having such a high overall response rate as well as complete response rate with almost more than half the patients staying in remission at six months is very helpful and beneficial for the classical Hodgkin lymphoma patients.

What is the clinical significance of these results?

This is a big significant step forward for patients with relapsed/refractory Hodgkin lymphoma. Remember that Hodgkin lymphoma treatment has evolved quite a bit over a period of time. We had ABVD, which was a very standard treatment, and then we had the brentuximab coming in which is a CD30-directed antibody drug conjugate combined with AVD which showed actually a survival benefit when they compared it to ABVD. Then SWOG-1826 came in which actually combined nivolumab with AVD in a front-line setting.

So what is happening with this change in the standard of care treatment with classical Hodgkin lymphoma is that most of these patients are now exposed to multiagent chemotherapy, brentuximab vedotin and classical PD-1 inhibitor. All of this, if they fail all of this, which are a small portion of patients, their treatment options are very, very limited. This is a robust and a good combination and there are many benefits to this combination. One, again, it is very active as we discuss in this abstract in relapsed/refractory Hodgkin lymphoma patients. Two, this can be done in outpatients, none of the patients were admitted in the hospital. Three, all of this treatment, unlike CAR-T where there is a lag, T-cells have to be prepared, all of these are available off the shelf. So the patients can get it right away. The toxicity was manageable, it was not very high at the cost. So typically when I look at this kind of combination I make sure that the benefit patients are getting is not at the cost of toxicity which was not the case.

So there are multiple benefits of this combination for relapsed/refractory classical Hodgkin lymphoma patients.