ASH 2023 | Subcutaneous alnuctamab in patients with R/R multiple myeloma: the results of a Phase I trial
Noffar Bar, MD, Yale School of Medicine, New Haven, CT, presents updated results from a Phase I trial (NCT03486067) of alnuctamab, a 2+1 BCMA x CD3 T-cell engaging antibody, in patients with relapsed/refractory (R/R) multiple myeloma (MM). Although the agent was initially administered intravenously, this resulted in a high incidence of cytokine release syndrome (CRS) and subcutaneous (SC) administration was opted for instead. Dr Bar discusses the safety and efficacy data currently available from the trial, including overall response rate (ORR), progression-free survival (PFS), rate of CRS and infections, and incidence of immune effector cell-associated neurotoxicity syndrome (ICANS). This interview took place at the 65th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (edited for clarity)
So, I presented the updated results of the Phase I study of subcutaneous alnuctamab in relapsed/refractory myeloma patients who had three or more lines of therapy. Now, what’s unique about this product? It’s a BCMA BiTE, but it has two binding sites on BCMA, which makes it unique from the other FDA-approved BCMA BiTEs. Also, the schedule is a little bit different, where we give two step-up dosing and then the target dose on day eight and then weekly dosing for three cycles and then every other week dosing for the next three cycles, and with cycle seven, you’re actually going to monthly treatment...
So, I presented the updated results of the Phase I study of subcutaneous alnuctamab in relapsed/refractory myeloma patients who had three or more lines of therapy. Now, what’s unique about this product? It’s a BCMA BiTE, but it has two binding sites on BCMA, which makes it unique from the other FDA-approved BCMA BiTEs. Also, the schedule is a little bit different, where we give two step-up dosing and then the target dose on day eight and then weekly dosing for three cycles and then every other week dosing for the next three cycles, and with cycle seven, you’re actually going to monthly treatment. So those are some of the key features that makes this a little bit different than the other BiTEs. Now at a median follow-up -let’s start with the efficacy- at a median follow-up of about a year, 11.7 months, there was an overall response rate in the 30-milligram target dose of 67%, which is very promising. And what is even nicer is that most of those responses are durable, so the majority of the patients are still having ongoing response to this state. The median progression-free survival for that 30 milligram target dose is 10.4 months. Those are the efficacy results.
Now, when we look at the safety profile, it’s also quite manageable actually. So the main things we’re looking at are CRS rates, so that was 55% at the 30-milligram target dose and the majority of those were manageable, so only grade one and two and no grade three toxicity and CRS. Infections, also something that might be a result of not [having] as long of a follow-up as with the other bispecifics, but we only saw 17% of severe infections, so grade three and above. So that was encouraging, but again more follow-up will be needed. Now, neurotoxicity was only seen in two patients, what we’d describe as ICANS, and it was all grade one and resolved. So this drug is very manageable, has a good safety profile, comparable if not slightly better in terms of infection risk (again, hard to compare, we need a longer follow-up), and the efficacy is very promising. And again the median duration of response has not been reached. So, I think we’re very excited to see a longer-term follow-up. There is a Phase III that is now currently in development in the earlier lines.
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