ASH 2023 | MRD clearance in response to HMA + sabatolimab in HR-MDS: insights from STIMULUS-MDS1
Uwe Platzbecker, MD, University of Leipzig, Leipzig, Germany, shares findings from the Phase II STIMULUS-MDS1 trial (NCT03946670), with a focus on measurable residual disease (MRD) responses to hypomethylating agent (HMA) plus sabatolimab or placebo in patients with higher-risk myelodysplastic syndromes (HR-MDS). Despite not meeting the primary endpoint, the HMA plus sabatolimab arm demonstrated a more substantial and prolonged reduction in MRD, indicating clinical activity of this combination approach. These findings will be investigated further in the ongoing Phase III STIMULUS-MDS2 study (NCT04266301). 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)
The next abstract deals with a combination therapy for high-risk MDS patients, namely HMA-based therapy plus a checkpoint inhibitor, which is actually a TIM-3 inhibitor, sabatolimab. There was a very encouraging Phase I/II study, which resulted in a Phase II trial, a randomized placebo-controlled trial: HMA versus HMA plus sabatolimab. And the results of this study have been presented at the last ASH meeting and are also in press at the Lancet Hematology currently, but this analysis now presented at the ASH is actually dealing with MRD, so looking for the decline of the allelic burden of mutations over time...
The next abstract deals with a combination therapy for high-risk MDS patients, namely HMA-based therapy plus a checkpoint inhibitor, which is actually a TIM-3 inhibitor, sabatolimab. There was a very encouraging Phase I/II study, which resulted in a Phase II trial, a randomized placebo-controlled trial: HMA versus HMA plus sabatolimab. And the results of this study have been presented at the last ASH meeting and are also in press at the Lancet Hematology currently, but this analysis now presented at the ASH is actually dealing with MRD, so looking for the decline of the allelic burden of mutations over time.
Just to remind you, there was a difference in favor of the CR rate with the aza/decitabine/sabatolimab arm in favor of the combination, but this was not statistically significant. And there was also a trend for a better disease-free survival, so for longer durability.
So there were more patients in the combination arm achieving an MRD response, so with regards to a decline of the allelic burden of disease-specific mutations, and also these patients had a longer durability of response. Suggesting, although the trial did not meet the primary endpoint, that there is a disease-modifying activity of the combination with HMA plus sabatolimab, and this may also explain the clinical observation that durability was improved.
There’s actually also a Phase III trial, let’s say ongoing or has not been reported, and we hope that the results of this STIMULUS program, the Phase III, will show encouraging results not only with regards to CR and response rate, but also other endpoints of the trial.
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Disclosures
Consultancy: AbbVie, Novartis, Jazz, Bristol Myers Squibb, Servier, Janssen Biotech, Syros, Amgen, Curis, Geron, Silence Therapeutics, Takeda
Honoraria: Novartis, Jazz, Bristol Myers Squibb, Servier, Syros, Celgene, Silence Therapeutics, Takeda
Research Funding: Novartis, Roche, BeiGene, Jazz, Bristol Myers Squibb, Servier, Janssen Biotech, Syros, Merck, Fibrogen, Amgen, Curis, Geron, BMS, Silence Therapeutics, Takeda
Board of Directors/Advisory Committee: MDS Foundation, Bristol Myers Squibb
Travel Support: Bristol Myers Squibb
Medical Writing Support: Bristol Myers Squibb
