S227928 / Servier, HitGen - LARVOL DELTA

S227928: A Novel Anti-CD74 ADC with MCL-1 Inhibitor Payload for the Treatment of Acute Myeloid Leukemia (AML) and Other Hematologic Malignancies (ASH 2024) - "Introduction Overexpression of MCL-1 is a well-known mechanism of resistance to venetoclax (ven), a BCL-2 inhibitor. Conclusion Given these promising data, S227928 should lead to an improved therapeutic index via more selective delivery of S64315 to CD74-expressing tumor cells. S227928 will be evaluated in a Phase 1/2 study as a single agent and in combination with ven for the treatment of patients with relapsed/refractory (R/R) AML or chronic myelomonocytic leukemia (CMML) who are no longer candidates for standard therapies."

IO biomarker • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Gastrointestinal Disorder • Hematological Malignancies • Leukemia • Mantle Cell Lymphoma • Oncology • CD34 • CD74 • MIF

CD74 Antibody Conjugated to an MCL1 Inhibitor (S227928) Combines Synergistically with Venetoclax to Enhance Killing of Acute Myeloid Leukemia (ASH 2024) - "Concordantly, viability of normal CD34+ cells was not significantly impacted by either S227928 alone or in combination with venetoclax, in contrast to the cytotoxic impact of cytarabine or daunorubicin on CD34+ cell viability. Importantly, this combination is active in TP53 mutated and monocytoid AML, sub-groups associated with venetoclax failure. These findings support the clinical development of S227928 alone and in combination in patients with AML."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • BCL2L1 • CD14 • CD20 • CD33 • CD34 • CD74 • KIT • TP53

A Study to Evaluate S227928 as a Single Agent and in Combination With Venetoclax in Patients With R/R AML, MDS/AML, or CMML (clinicaltrials.gov) - P1/2 | N=13 | Terminated | Sponsor: Servier Bio-Innovation LLC | N=132 ➔ 13 | Trial completion date: Aug 2030 ➔ Oct 2025 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2028 ➔ Oct 2025; Sponsor decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study to Evaluate S227928 as a Single Agent and in Combination With Venetoclax in Patients With R/R AML, MDS/AML, or CMML (clinicaltrials.gov) - P1/2 | N=132 | Recruiting | Sponsor: Servier Bio-Innovation LLC | Initiation date: Nov 2024 ➔ Feb 2025 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial initiation date • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

A Study to Evaluate S227928 as a Single Agent and in Combination With Venetoclax in Patients With R/R AML, MDS/AML, or CMML (clinicaltrials.gov) - P1/2 | N=132 | Not yet recruiting | Sponsor: Servier Bio-Innovation LLC

Combination therapy • New P1/2 trial • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology