2023
STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2
Zeidan A, Giagounidis A, Sekeres M, Xiao Z, Sanz G, Van Hoef M, Ma F, Hertle S, Santini V. STIMULUS-MDS2 design and rationale: a phase III trial with the anti-TIM-3 sabatolimab (MBG453) + azacitidine in higher risk MDS and CMML-2. Future Oncology 2023, 19: 631-642. PMID: 37083373, DOI: 10.2217/fon-2022-1237.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHigh-risk myelodysplastic syndromeChronic myelomonocytic leukemiaMyelodysplastic syndromeCMML-2Tim-3Hematopoietic stem cell transplantationT-cell immunoglobulin domainMucin domain 3Risk myelodysplastic syndromesPhase III trialsStem cell transplantationLeukemic stem cellsFavorable tolerabilityIII trialsNovel immunotherapiesPoor outcomeCell transplantationLeukemic blastsClinical trialsNovel therapiesMyelomonocytic leukemiaDurable benefitImmune systemMyeloid malignanciesMeaningful improvements
2022
AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML)
Zeidan A, Westermann J, Kovacsovics T, Assouline S, Schuh A, Kim H, Macias G, Sanford D, Luskin M, Stein E, Malek K, Lyu J, Stegert M, Esteve J. AML-484 First Results of a Phase II Study (STIMULUS-AML1) Investigating Sabatolimab + Azacitidine + Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia (ND AML). Clinical Lymphoma Myeloma & Leukemia 2022, 22: s255. DOI: 10.1016/s2152-2650(22)01303-9.Peer-Reviewed Original ResearchTreatment-related AEsDose-escalation partDose-limiting toxicityIntensive chemotherapyDosage reductionCohort 2Acute myeloid leukemiaDose interruptionFebrile neutropeniaSerious AEsExpansion cohortStudy patientsTreatment discontinuationAdult patientsDurable responsesNeutrophil countTim-3Agent therapyMyelodysplastic syndromePlatelet countSafety profilePatient outcomesMyeloid leukemiaPatientsDay 1MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Ma F, Iordan A, Sabo J, Garcia-Manero G. MDS-476 Sabatolimab (MBG453) Combination Treatment Regimens for Patients With Higher-Risk Myelodysplastic Syndromes (HR-MDS): The Myelodysplastic Syndromes Studies in the STIMULUS Immuno-Myeloid Clinical Trial Program. Clinical Lymphoma Myeloma & Leukemia 2022, 22: s317. DOI: 10.1016/s2152-2650(22)01420-3.Peer-Reviewed Original ResearchHematopoietic stem cell transplantLeukemia-free survivalPhase II trialHigh-risk myelodysplastic syndromeHR-MDS patientsClinical trial programII trialLeukemic stem cellsCombination therapyTim-3Trial programLeukemic cellsTransfusion-free intervalEvent-free survivalPhase III trialsStem cell transplantOverall response rateEarly phase trialsNovartis Pharmaceuticals CorporationImprovement of fatigueExpansion cohortIntensive chemotherapyPrimary endpointDurable responsesIII trialsAre We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia?
Shallis RM, Bewersdorf JP, Stahl MF, Halene S, Zeidan AM. Are We Moving the Needle for Patients with TP53-Mutated Acute Myeloid Leukemia? Cancers 2022, 14: 2434. PMID: 35626039, PMCID: PMC9140008, DOI: 10.3390/cancers14102434.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAcute myeloid leukemiaMyeloid leukemiaAllogeneic hematopoietic stem cell transplantationHematopoietic stem cell transplantationCD47/SIRPαIntensive induction therapyAvailable therapeutic optionsStem cell transplantationStandard of careAvailable clinical dataTesting of agentsInduction therapyMedian overallRefractory settingAggressive treatmentTim-3Immune checkpointsPreclinical rationaleTherapeutic optionsCell transplantationEfficacy dataClinical dataPatientsMolecular subgroupsTherapeutic agents
2021
Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program
Zeidan A, Al-Kali A, Borate U, Cluzeau T, DeZern A, Esteve J, Giagounidis A, Kobata K, Lyons R, Platzbecker U, Sallman D, Santini V, Sanz G, Sekeres M, Wei A, Xiao Z, Van Hoef M, Nourry-Boulot C, Sadek I, Bengoudifa B, Sachs C, Sabo J, Garcia-Manero G. Sabatolimab (MBG453) Combination Treatment Regimens for Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS): The MDS Studies in the Stimulus Immuno-Myeloid Clinical Trial Program. Blood 2021, 138: 4669. DOI: 10.1182/blood-2021-145626.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeClinical Trials CommitteeProgression-free survivalHematopoietic stem cell transplantLeukemia-free survivalClinical trial programLeukemic stem cellsComplete responsePrimary endpointOverall survivalTim-3Trials CommitteeHMA therapySecondary endpointsII trialAdverse eventsNovartis Pharma AGCombination therapyMyeloid malignanciesTrial programSpeakers bureauBristol-Myers SquibbIntensive chemotherapyPartial remissionTarget enrollment
2020
The STIMULUS Program: Clinical Trials Evaluating Sabatolimab (MBG453) Combination Therapy in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML)
Zeidan A, Esteve J, Giagounidis A, Kim H, Miyazaki Y, Platzbecker U, Schuh A, Sekeres M, Westermann J, Xiao Z, Malek K, Scott J, Niolat J, Peyrard S, Ma F, Kiertsman F, Stegert M, Hertle S, Fenaux P, Santini V. The STIMULUS Program: Clinical Trials Evaluating Sabatolimab (MBG453) Combination Therapy in Patients (Pts) with Higher-Risk Myelodysplastic Syndromes (HR-MDS) or Acute Myeloid Leukemia (AML). Blood 2020, 136: 45-46. DOI: 10.1182/blood-2020-134718.Peer-Reviewed Original ResearchHigh-risk myelodysplastic syndromeHematopoietic stem cell transplantationAcute myeloid leukemiaEvent-free survivalLeukemic stem cellsIntensive chemotherapyOverall survivalPrimary endpointSecondary endpointsCurrent equity holderEligible ptsTim-3Transfusion independenceCombination therapyEastern Cooperative Oncology Group performance statusCR/CRi rateEncouraging overall response rateAdvisory CommitteeDaiichi SankyoDuration of CRTransfusion-free intervalLeukemia-free survivalComplete remission rateHigh-risk MDSProgression-free survival
2019
A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of MBG453 Added to Hypomethylating Agents (HMAs) in Patients (pts) with Intermediate, High, or Very High Risk Myelodysplastic Syndrome (MDS): Stimulus-MDS1
Zeidan A, Miyazaki Y, Platzbecker U, Malek K, Niolat J, Kiertsman F, Fenaux P. A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of MBG453 Added to Hypomethylating Agents (HMAs) in Patients (pts) with Intermediate, High, or Very High Risk Myelodysplastic Syndrome (MDS): Stimulus-MDS1. Blood 2019, 134: 4259. DOI: 10.1182/blood-2019-127041.Peer-Reviewed Original ResearchLeukemia-free survivalProgression-free survivalAcute myeloid leukemiaHR-MDSMyelodysplastic syndromeOverall survivalHypomethylating agentTim-3Leukemic stem cellsClinical trialsHigh riskGood safety/tolerability profileInternational Working Group 2006 criteriaSolid tumorsDiagnosis of AMLAllogeneic hematopoietic stem cell transplantationMulticenter phase II clinical trialPrior treatmentAnti-Tim-3 antibodyIPSS-R risk categorySafety/tolerability profileCelgene CorporationTherapy-related myelodysplastic syndromeHigh-risk myelodysplastic syndromeInternational Prognostic Scoring System