Karyopharm Therapeutics, a clinical-stage pharmaceutical company, has announced the results of a planned interim analysis of the phase II SOPRA study evaluating single agent selinexor in relapsed/refractory acute myeloid leukemia (AML). The company determined in concert with the study’s independent Data Safety Monitoring Board (DSMB) that SOPRA will not reach statistical significance for overall survival (OS), the study’s primary endpoint.
However, since selinexor-treated patients that achieved a complete response (CR) showed a substantial OS benefit as compared with the physician’s choice (PC) arm, Karyopharm and the DSMB agreed that patients would be permitted to continue on the selinexor arm or the PC arm, as applicable, following discussion between the patient and their treating physician. The Company plans to continue clinical development of selinexor in AML through investigator sponsored trials in multiple combination regimens, including with chemotherapy, given encouraging data to date across these settings.
SOPRA is a phase II randomized study of patients 60 years of age or older with relapsed or refractory AML who were ineligible for intensive chemotherapy and/or transplantation. Patients were randomized to either receive single-agent oral selinexor 60mg twice weekly or PC. PC included best supportive care (BSC) alone, or BSC plus either azacitidine (Vidaza), decitabine (Dacogen), or low dose cytosine arabinoside (LD-AraC). Based on unaudited site data, SOPRA enrolled 176 patients (median of two prior regimens) in the U.S., Canada, Europe and Israel.
Among patients on the selinexor arm, 13% demonstrated a CR with or without full hematologic recovery (CRi) compared to 3% of patients on the PC control arm. Some patients remained on selinexor for over one year, but this did not result in a statistically superior OS compared to the PC arm. The DSMB found no new clinically significant adverse events in the patients receiving selinexor. Importantly, rates of sepsis and febrile neutropenia (FN) were lower on the selinexor arm (sepsis 4.9%, FN 14.7%) compared to the PC arm (sepsis 6.1%, FN 36.4%). As expected, the most common selinexor-related adverse events were nausea, anorexia, fatigue, vomiting, and thrombocytopenia. Patients who have benefited from selinexor treatment on the SOPRA study have the option to continue therapy.
“SOPRA is a robust, well-conducted trial and the response rates achieved with single-agent selinexor in this heavily pretreated older population have been encouraging,” said Hagop Kantarjian, M.D., chair of the Department of Leukemia, The University of Texas MD Anderson Cancer Center. “Importantly, the safety profile was as expected and the recommended Phase 2 dose was generally well-tolerated. Unfortunately, as is common in AML, the higher response rates observed with single-agent selinexor versus physician’s choice did not translate into extended survival in the overall population of these frail and heavily pretreated patients.”
“After performing an in-depth analysis, we and the DSMB agree that, despite the higher complete response rates observed with selinexor, the phase 2 SOPRA study evaluating single-agent selinexor in relapsed or refractory AML has not reached statistical significance for overall survival, the primary endpoint of the study,” said Michael G. Kauffman, M.D., Ph.D., chief executive officer of Karyopharm. “While we are disappointed with the overall outcome, we are pleased that 60mg of single-agent selinexor dosed twice per week was well-tolerated and carried no increased risk of sepsis or febrile neutropenia. At Karyopharm, our primary focus remains the advancement of selinexor in relapsed or refractory multiple myeloma, where we believe we have a clear path to regulatory approval.”
Dr. Kauffman continued, “Beyond myeloma, we see diffuse large B-cell lymphoma (DLBCL) and liposarcoma as high unmet need indications where selinexor has a meaningful opportunity for clinical success and where we are expecting key data readouts during 2017. We look forward to reporting top-line data from our randomized Phase 2b SADAL study evaluating single-agent selinexor in patients with relapsed or refractory DLBCL in early 2017 and top-line data from the phase II portion of the randomized phase II/III SEAL study evaluating single-agent selinexor in patients with advanced liposarcoma in mid-2017.”
Sharon Shacham, Ph.D., MBA, president and chief scientific officer of Karyopharm, commented, “We continue to believe selinexor has potential in AML, most likely in combination with other agents in front line and later settings. We continue to explore the use of selinexor in combination with novel and standard agents through investigator-sponsored AML studies. Clinical data recently reported at the 2016 American Society of Hematology annual meeting demonstrated that selinexor in combination with certain standard therapies, including intensive chemotherapy as well as hypomethylating agents, demonstrated encouraging activity in AML in adults, both as an initial therapy and in the relapsed setting. The benefit of selinexor in combination with intensive chemotherapy will be assessed in randomized investigator sponsored trials that we expect will begin in 2017. Furthermore, selinexor in combination with intensive chemotherapy has shown very promising responses in pediatric patients with heavily pretreated AML.”
“We are deeply grateful for the support and commitment of the AML investigators and the patients and families who have taken part in or contributed to the SOPRA study,” Dr. Shacham concluded.
The phase II SOPRA (Selinexor in Older Patients with Relapsed/Refractory AML) study is a randomized trial evaluating single-agent selinexor (KPT-330), Karyopharm's lead, novel, oral Selective Inhibitor of Nuclear Export / SINE compound, versus physician's choice in patients 60 years of age or older with relapsed or refractory AML who were ineligible for intensive chemotherapy and/or transplantation. In the SOPRA study, 176 patients with AML whose disease had relapsed after, or was refractory to, first line therapy were randomized 2:1 to receive either oral selinexor (60mg twice per week) or one of four physician’s choice (PC) therapies. Physician’s choice included best supportive care (BSC) alone, or BSC plus either azacytidine (Vidaza), decitabine (Dacogen), or low dose cytosine arabinoside (LD-AraC). The primary endpoint of the SOPRA study was overall survival (OS), with a target of a 75% improvement in OS from 3.0 months in the PC arm to 5.2 months in the selinexor arm. SOPRA was conducted at approximately 94 sites worldwide, including sites in the U.S., Canada, Europe and Israel.