Sanofi's CD38-Targeting Antibody Sarclisa + RVd Achieves High MRD Negativity Rate in Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients

December 24, 2021 /BioValleyBIOON/ -- Sanofi recently announced the results of the pivotal Phase 3 GMMG-HD7 trial. The trial involved newlyDiagnosisThe study was conducted in China, among patients with multiple myeloma (MM) who were eligible for transplantation. The results showed that the study met its primary endpoint: compared to patients receiving the standard care regimen of lenalidomide + bortezomib + dexamethasone (RVd), patients treated with the CD38-targeted antibody Sarclisa (isatuximab) + RVd regimen had a statistically significant improvement in minimal residual disease (MRD) negativity rate after induction therapy (18 weeks) and before transplantation.50.1% of patients reached undetectable disease levels, while the RVd control group was 35.6%. MRD negativity is an important clinical endpoint associated with better patient prognosis.

It is worth mentioning that,GMMG-HD7 trial is the first Phase 3 study to achieve MRD negativity in newly diagnosed MM patients eligible for transplantation.. At the same time, Sarclisa+RVd is the first in Phase 3Clinical TrialA regimen that shows superior efficacy to standard care (RVd) in China. MRD negativity is defined as the absence of myeloma cells in the bone marrow after treatment, as confirmed byDiagnosisTechnical measurement, with a sensitivity of at least 1/100,000. This assessment is the most sensitive tool for measuring the depth of treatment response in MM patients.

Hartmut Goldschmidt, Chief Investigator of the GMMG-HD7 trial, President of GMMG, and Professor of Medicine at Heidelberg University Hospital (UKHD), Germany, stated: "Achieving MRD negativity in half of the patients this early in the treatment regimen is unprecedented. We know that achieving deeper remission earlier in treatment may translate into longer progression-free survival (PFS), and we are excited about these results."

SanofiTumorGlobal Development Head Peter C. Adamson stated: "The results of this trial reinforce our belief in the potential of Sarclisa to become the preferred anti-CD38 drug. Observing such a high proportion of MRD-negative patients after a relatively short induction period is very encouraging. We look forward to continuing our collaboration with GMMG to advance new...Diagnosis"Patients with multiple myeloma have potential treatment options."

The GMMG-HD7 trial, initiated by the German Myeloma Multicenter Group (GMMG) and conducted in close collaboration with Sanofi, is a randomized, open-label, multicenter, two-part Phase 3 trial that enrolled 662 newly diagnosed patients across 67 clinical centers in Germany.DiagnosisThe, MM patients who meet the transplant criteria. In the first part of the study, all patients were evenly randomized into two treatment groups, both receiving three cycles (42 days per cycle) of RVd treatment, with one group also receiving Sarclisa. The Sarclisa dosing regimen was: 10mg/kg dose administered once weekly via intravenous infusion during the first four weeks of the first cycle, followed by once every two weeks for the remainder of the induction period. MRD negativity was assessed post-induction using next-generation flow cytometry (cut-off value of 1x10E-5), and odds ratios were used to measure this endpoint to determine the association between adding Sarclisa to standard of care and achieving MRD negativity in patients.

The primary endpoint is the MRD negativity rate after induction therapy in the first part of the study, and progression-free survival (PFS) after the second randomization post-transplant in the second part of the study, with Sarclisa added to lenalidomide maintenance therapy. Secondary endpoints include the complete response rate (CR) after induction, overall survival (OS) after maintenance therapy, and safety.

The results showed,After an 18-week induction period (3x42 days), the MRD negativity rate was 50.1% in the patient group receiving Sarclisa combination therapy (n=331), compared to 35.6% in the patient group receiving RVd (n=329).(Odds Ratio [OR]=1.83; 95% CI: 1.34-2.51; p<0.001). The safety and tolerability of Sarclisa observed in this study were consistent with otherClinical TrialThe safety profile of Sarclisa observed in China was consistent, with no new safety signals identified. The incidence of all adverse events observed was 63.6% in the Sarclisa combination therapy group and 61.3% in the RVd treatment group, with serious adverse events reported in both study groups.Adverse ReactionsSimilar discontinuation rates (34.8% vs 36.3%, respectively). However, during the induction period, there were more deaths in the RVd group (1.2% vs 2.4%). After the second randomization, the trial is ongoing to evaluate progression-free survival (PFS) with Sarclisa + lenalidomide as maintenance therapy.

The active pharmaceutical ingredient in Sarclisa, isatuximab, is an IgG1 chimeric monoclonal antibody,Targeting specific epitopes of CD38 receptors on plasma cells can trigger multiple unique mechanisms of action.Including the promotion of programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly expressed on multiple myeloma (MM) cells and serves as a cell surface receptor target for antibody therapy in MM and other malignancies. In the United States and the European Union, isatuximab has been granted orphan drug status for the treatment of relapsed or refractory multiple myeloma (R/R MM). Currently, Sanofi is also evaluating isatuximab for the treatment of other hematologic malignancies.TumorAnd the potential of solid tumors.

In March 2020, Sarclisa received U.S.FDAApproved in combination with pomalidomide and dexamethasone (pom-dex) for adult patients with relapsed and refractory multiple myeloma (RRMM) who have previously received at least two prior therapies, including lenalidomide and a proteasome inhibitor. In early June 2020, the Sarclisa in combination with pom-dex regimen also received approval from the European Commission (EC).

Sarclisa is the first direct competitor to Johnson & Johnson's重磅 CD38-targeted drug Darzalex.The latter was launched in 2015, with indications covering first- to fourth-line treatments, and has become a cornerstone therapy in clinical practice. In 2020, its global sales reached $4.19 billion, marking a 39.8% increase from the previous year. Analysts at Wall Street investment bank Jefferies projected that Sarclisa’s annual sales peak post-launch would exceed $1 billion.

Currently, Sanofi is advancing multiple Phase III clinical trials to evaluate isatuximab in combination with currently available standard therapies for the treatment of RRMM patients or newly diagnosed patients.DiagnosisMM patients. MM is the second most common hematological malignancyTumor, with more than 1.38 million new cases diagnosed globally each year. For the majority of patients, MM remains incurable, representing a significant unmet medical need in this field. (Bioon.com)

Source of the original text:Sarclisa (isatuximab) trial is first Phase 3 study to meet primary endpoint of minimal residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma