Phase 3 IRAKLIA Trial Compares On-Body vs IV Isatuximab in RRMM: Xavier Leleu, MD, PhD

During part 1 of an interview at the European Hematology Association Congress in Milan, Xavier Leleu, MD, PhD, head of the Department of Haematology and the Myeloma Clinic at Hôpital La Mileterie, in Poitiers, France, discusses the background and objectives of the phase 3 IRAKLIA trial (NCT05405166).

As the lead investigator, Leleu presented this information from the abstract titled, "Isatuximab Subcutaneous Via an On-Body Delivery System Versus Isatuximab Intravenous, Plus Pomalidomide and Dexamethasone, in Relapsed/Refractory Multiple Myeloma: The Randomized Phase 3 IRAKLIA Study,” today during the session, "Treatment of Relapsed and/or Refractory Multiple Myeloma (RRMM)."

This transcript was lightly edited; captions were auto-generated.

Transcript

For context, could you summarize the initial advantages of subcutaneous isatuximab delivered via an on-body delivery system observed in the phase 1b study among patients with relapsed/refractory multiple myeloma?

We found out in the past 10 years that the CD38 monoclonal antibody is an immunotherapy that has absolutely transformed the field of myeloma [and] the survival of the patients. It has been associated [with] any type of regimen, triplet-, quadruple-based regimens, and it's so effective that we have no doubt that the CD38 monoclonal antibody will stay around for very long.

Now, there are only 2 of them, daratumumab and isatuximab. Daratumumab is [a] manual push sub-q [subcutaneous injection]. Isatuximab is, right now, IV [intravenous]. The CD38 monoclonal antibodies, they have a very good safety profile, so they are given for very long. Myeloma becomes, for many patients, a chronic disease, but chronic means long-term treatment to control this chronic disease and not make a disease that will relapse.

To give an IV isatuximab injection fusion for very long, it's not very convenient for the patients. It's not very convenient for the teams, particularly in an ambulatory way of giving the drugs in [an] outpatient clinic. We need something simpler, we need something faster, we need something more convenient for everyone.

The development of a sub-q formulation of isatuximab was inevitable. The question was, would it be a manual push, like daratumumab, or could it be actually thought much better, something much more convenient? Can we improve sub-q with another sub-q formulation, [make it] even better?

That's exactly what the OBI, on-body injector, a type of on-body delivery system, is about. That's exactly why we think isatuximab, with subcutaneous formulation, with the OBI, is such important progress for the patients, for their families, and for the teams in the field of myeloma.

Building on that foundation, what was the objective of the phase 3 IRAKLIA study? What methods were used to investigate this?

At some point, the pharmaceutical company Sanofi is going to have the isatuximab formulation approved, so it could be scientifically scored, it could be reimbursed, and so they had to build a phase 3 study, noninferiority, where they would be able to demonstrate that the isatuximab sub-q formulation with OBI would be noninferior to the IV. Now, if it was noninferior, efficacy-wise, but much better safety- and quality of life–wise, why wouldn't I be using isatuximab sub-q vs IV?

In the context of a free registrational study, you need to use a regimen that is already approved. It was not very difficult to pick isatuximab [plus] pom [pomalidomide]-dex [dexamethosone]. They built a study, 2 arms, randomized 1:1, isatuximab/pom-dex with isatuximab IV control arm vs [the] experimental arm, isatuximab/pom-dex with isatuximab subcutaneous formulation with the OBI.

Then, they ran the study. [The] co-primary end point, overall response rate, as the primary end point, so efficacy one, and Ctrough, sort of minimal serum concentration at steady state, pre-cycle 6 dose, which is a requirement by [the] FDA.

Then, they had a series of key secondary end points, with VGPR [very good partial response], or better, with [the] safety profile, with quality of life, and with an earlier time point of Ctrough, minimal serum concentration earlier on cycle 2 to see if the immediate effect on myeloma would be good, if the minimal serum concentration of the drug would be really great earlier.