Drug may be new option for difficult-to-treat DLBCL, doc says

Micrograph showing DLBCL

WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.

Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.

Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.

The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.

Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*

The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.

Patients and treatment

The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.

The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.

60 mg arm

There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.

Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.

100 mg arm

There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.

Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.

Safety

All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).

These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.

The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.

Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).

Efficacy

Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).

The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).

The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:

The median duration of response was greater than 7 months. The median time to response was 2 months.

Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.

The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.

“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.

Trial update

As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.

SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.

The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.

Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.

The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.

The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

*Data in the abstract differ from the presentation.

Micrograph showing DLBCL

WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.

Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.

Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.

The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.

Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*

The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.

Patients and treatment

The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.

The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.

60 mg arm

There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.

Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.

100 mg arm

There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.

Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.

Safety

All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).

These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.

The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.

Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).

Efficacy

Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).

The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).

The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:

The median duration of response was greater than 7 months. The median time to response was 2 months.

Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.

The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.

“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.

Trial update

As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.

SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.

The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.

Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.

The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.

The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

*Data in the abstract differ from the presentation.

Micrograph showing DLBCL

WASHINGTON, DC—Selinexor has demonstrated the potential to become a new oral treatment option for patients with difficult-to-treat diffuse large B-cell lymphoma (DLBCL), according to a presenter at the AACR Annual Meeting 2017.

Interim results from the phase 2b SADAL study showed that selinexor produced a 28.6% overall response rate (ORR), with an 11.1% complete response (CR) rate, in a heavily pretreated, older DLBCL population.

Responses were observed in GCB and non-GCB subtypes, and the median duration of response exceeded 7 months.

The most common adverse events (AEs) were fatigue, thrombocytopenia, nausea, anorexia, and vomiting.

Marie Maerevoet, MD, of the Institute Jules Bordet in Brussels, Belgium, presented data from the SADAL study as abstract CT132/13.*

The trial is sponsored by Karyopharm Therapeutics, the company developing selinexor.

Patients and treatment

The study enrolled 72 patients with relapsed or refractory DLBCL. At least 14 weeks had elapsed since their most recent systemic anti-DLBCL therapy.

The patients received selinexor—an oral selective inhibitor of nuclear export (SINE™) compound—at 60 mg or 100 mg twice weekly (days 1 and 3 each week) of each 28-day cycle.

60 mg arm

There were 37 patients in the 60 mg arm. Their median age was 71 (range, 38-87), and most (n=24) were male. Forty-nine percent of these patients (n=18) had GCB DLBCL.

Fourteen percent of patients had high-risk disease (according to the revised international prognostic index). Forty-three percent had high-intermediate-risk, 30% had low-intermediate-risk, and 14% had low-risk disease.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Twenty-seven percent had received a prior transplant.

100 mg arm

There were 35 patients in the 100 mg arm. Their median age was 68 (range, 32-82), and most (n=23) were male. Fifty-one percent of patients (n=18) had GCB DLBCL.

Eleven percent of patients had high-risk, 40% had high-intermediate-risk, 37% had low-intermediate-risk, and 6% had low-risk disease. For 6% of patients, their risk group was unknown.

The patients had received a median of 3 prior treatment regimens (range, 2-5). Forty-six percent had received a prior transplant.

Safety

All 72 patients were evaluable for safety. The most common AEs across both dosing groups were fatigue (65%), thrombocytopenia (54%), nausea (51%), anorexia (49%), vomiting (35%), and anemia (32%).

These events were primarily grades 1 and 2 and were managed with dose modifications and/or standard supportive care.

The 60 mg dose was better tolerated than the 100 mg dose, with fewer dose interruptions and modifications required in the 60 mg arm.

Grade 3/4 AEs that were more common in the 100 mg arm than the 60 mg arm were fatigue (26% vs 11%), thrombocytopenia (46% vs 32%), and anorexia (11% vs 3%).

Efficacy

Sixty-three patients were analyzed for response. The ORR was 28.6% (18/63), with a CR rate of 11.1% (n=7) and a partial response (PR) rate of 17.5% (n=11).

The rate of stable disease (SD) was 14.3% (n=9), and the rate of progressive disease (PD) was 46% (n=29). Seven patients (11.1%) were not evaluable (NE).

The best responses as of March 1, 2017, according to subtype and selinexor dose, were as follows:

The median duration of response was greater than 7 months. The median time to response was 2 months.

Among responders, the median time on treatment was 9 months, with a median follow-up of 13 months. As of the data cutoff date, 9 responders remained on treatment, including 6 patients with a CR.

The median overall survival was 8 months for all patients. As of the cutoff date, the median survival for the responders had not been reached.

“With the impressive and durable responses observed to date, including in both the GCB and non-GCB subtypes of DLBCL, single-agent selinexor is demonstrating the potential to become a new oral option for this difficult-to-treat patient population who are not candidates for transplantation and whose disease is unlikely to respond to further chemotherapy or targeted agents,” Dr Maerevoet said.

Trial update

As a result of the interim data from SADAL, and in consultation with the US Food and Drug Administration (FDA), Karyopharm is amending the study protocol.

SADAL will become a single-arm study focusing solely on single-agent selinexor dosed at 60 mg twice weekly.

The study is also being amended to reduce the 14-week treatment-free period to 8 weeks in patients who achieved at least a PR on their most recent therapy. Patients who were refractory to or did not achieve at least a PR on their prior therapy will continue with the 14-week treatment-free period.

Karyopharm plans to enroll up to an additional 90 patients to the new 60 mg single-arm cohort and expects to report top-line results from the SADAL study in mid-2018.

The FDA recently lifted a partial clinical hold placed on the SADAL trial and other trials of selinexor.

The FDA had placed the hold due to a lack of information in the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.

*Data in the abstract differ from the presentation.