– Results showed an overall response rate (ORR) of 3% for all treated patients.
– Consistent responses across all risk groups, including patients who received prior “triple-class” and CAR-T therapies or having cytogenetic abnormalities.
– Selinexor is on track for a Q2:22 launch in China.
Shanghai and Hong Kong, PRC, April 6, 2022 — Antengene Corporation Limited (“Antengene” SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing, and commercializing first-in-class and/or best-in-class medicines for cancer, today announced that results of its pivotal MARCH bridging study to evaluate selinexor in patients with relapsed/refractory multiple myeloma (R/R MM) were published in BMC Medicine. (https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02305-4)
MARCH study was a single-arm, open-label study to evaluate selinexor combined with low dose dexamethasone, the “Sd regimen”, for treatment of heavily pre-treated patients in China with R/R MM who were refractory to prior therapies with an immunomodulatory agent (IMiD) and a proteasome inhibitor (PI). The study also evaluated several high risk patient subgroups, such as triple-class refractory [refractory to PI, IMiD and anti-CD38 monoclonal antibody (mAb)] patients.
The primary endpoint for the study was ORR per an independent review committee. The ORR was 29.3% [95% Confidence Interval (CI): 19.7, 40.4] for all treated patients in the study. Antengene also reported the ORR for several high-risk subgroups including patients who had:
– Triple-class refractory disease: ORR = 25.0% (95% CI: 8.7, 49.1)
– Received prior CAR-T: ORR = 50.0% (95% CI: 18.7, 81.3)
– High-risk cytogenetic abnormalities: ORR = 25.5%
MARCH study was designed as a confirmatory bridging study to validate the data from the global Phase II STORM study. It addresses the China regulatory need to further validate the data from the STORM trial in Chinese patients with R/R MM.
The approval of selinexor in the U.S. was based on the STORM study, which demonstrated a significant clinical benefit of the Sd regimen in patients with R/R MM who had disease refractory to at least two PI, at least two IMiD, and an anti-CD38 mAb.
“The MARCH study was the cornerstone of the accelerated approval for selinexor for R/R MM in China, confirming the results from the US STORM trial. As Antengene is ready to launch selinexor in the second quarter of this year, we are very pleased to publish and share a full summary of the results of this pivotal trial with the medical community,” said Kevin Lynch, M.D., Chief Medical Officer of Antengene. “Antengene is very excited to bring this new therapeutic option for R/R MM to improve the care of patients in China.”
The pivotal MARCH trial was conducted at 17 sites in China. Selinexor 80 mg combined with dexamethasone 20 mg were administered orally on Day 1 and Day 3 of each week in 4‑week cycles.
Other secondary outcome measures included assessment of duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and pharmacokinetic (PK) profile.
A total of 82 Chinese patients with R/R MM were enrolled, with a median age of 60 years. Of the 82 patients, 55 patients (67.1%) had high-risk cytogenetic abnormalities and 18 patients (22.0%) had abnormal renal function. Enrolled patients were heavily pre-treated, having received a median prior regimen number of 5. All 82 patients (100%) were refractory to both PI and IMiD, including 20 patients (24.4%) categorized as triple-class refractory population. Ten patients (12.2%) had undergone CAR-T therapy.
Result showed that ORR was 29.3% (95% CI: 19.7, 40.4) with a median DOR of 4.7 months. The median PFS and OS were 3.7 months and 13.2 months, respectively. ORR was 25.0% in the triple-class refractory population. Efficacy was consistent across various subgroups. The PK profile was characterized by parameter and ethnicity sensitivity analyses. No significant drug accumulation was shown following multiple administrations. No human PK ethnicity difference was identified between Chinese and western patients.
Adverse events (AEs) found in the study were expected and manageable with supportive care and dose modification. The most frequent Grade 3/4 AEs included anemia (57.3%), thrombocytopenia (51.2%), lymphopenia (42.7%), neutropenia (40.2%), hyponatremia (29.3%) and lung infection (26.8%). Serious AEs were reported in 54.9% of patients.
About Multiple Myeloma
Multiple Myeloma (MM) is the second most common hematological malignancy, estimated about 15,000-20,000 new MM patients and 10,300 deaths in China per year.
Selinexor is the first and only oral XPO1 inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory multiple myeloma (R/R MM) and relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). By blocking the nuclear export protein XPO1, selinexor can promote the intranucl accumulation and activation of tumor suppressor proteins and growth regulating proteins, and down-regulate the levels of multiple oncogenic proteins. Due to its novel mechanism of action, selinexor is being evaluated for use in multiple combination regimens to improve treatment efficacy.
Antengene secured approval of selinexor in China in December 2021 for R/R MM and plans to launch the product in the second quarter of 2022. Antengene also secured approval for selinexor in South Korea for use in R/R MM and R/R DLBCL in July 2021, in Singapore for use in R/R MM and R/R DLBCL and in Australia for use in R/R MM in March 2022. Antengene is conducting 10 clinical studies in mainland China (3 in collaboration with Karyopharm) for relapsed/refractory hematological malignancies and advanced solid tumors.
Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on innovative first-in-class/best-in-class therapeutic medicines for cancer and other life-threatening diseases. Driven by its vision of “Treating Patients Beyond Borders”, Antengene aims to provide the most advanced anti-cancer drugs to patients in the Asia Pacific Region and around the world. Since initiating operations in 2017, Antengene has obtained 23 investigational new drug (IND) approvals in the US and in Asia, submitted 6 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for selinexor/ATG-010/XPOVIO® in China, South Korea, Singapore and Australia approved. Leveraging partnerships as well as in-house drug discovery, Antengene has built a broad and expanding pipeline of 15 clinical and pre-clinical assets. Antengene has global rights on 10 programs and Asia Pacific rights, including the Greater China region, on 5 programs.
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. Statistics released by the International Myeloma Foundation at https://www.myeloma.org/