PHASE 2 STUDY OF DARATUMUMAB MONOTHERAPY IN PATIENTS WITH ?3 LINES OF PRIOR THERAPY OR DOUBLE REFRACTORY MULTIPLE MYELOMA: 54767414MMY2002 (SIRIUS)
(Abstract release date: 05/31/15)
EHA Library. Lonial S. 06/13/15; 103136; S430
Disclosure(s): Winship Cancer Institute, Emory UniversityDepartment of Hematology and Medical Oncology
Prof. Sagar Lonial
Contributions
Contributions
Abstract
Abstract: S430
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:30 to 13.06.2015 12:45
Location: Room A2+3
Background
Novel agents including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs) have provided improved treatment outcomes for patients with multiple myeloma (MM). The majority of patients with MM still unfortunately relapse, with very limited options after PI and IMiD-based treatment. Daratumumab (DARA) is a human anti-CD38 IgG1κ mAb and has previously shown single agent activity and good tolerability in relapsed/refractory MM (Lokhorst HM et al. ASCO 2014).
Aims
This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and IMiD. Preliminary results are reported.
Methods
MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw for 8 weeks, q2w for 16 weeks, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC).
Results
Data for the 16 mg/kg DARA group are presented (n = 106). The median time from diagnosis was 4.8 years and patients received a median of 5 prior treatment lines. A total of 80% of patients received prior autologous stem cell transplants. Seventy five percent of patients were ISS stage 2 or higher. Ninety-six percent of patients were refractory to their last line of therapy and 95% were refractory to their last PI and IMiD. The proportions of patients refractory to other to agents included pomalidomide (63%), carfilzomib (48%) and alkylating agents (78%). Adverse events (AE; ≥20%) included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during the first infusion with 4.7% of patients with grade 3 IRRs. No grade 4 IRRs were reported and no patients discontinued the study due to IRRs. Five patients (4.7%) discontinued treatment due to AEs and none of these AEs were assessed by the investigator to be DARA-related. The ORR (IRC assessed) was 29.2%, with 3 stringent complete responses, 10 very good partial responses, and 18 partial responses. The ORR was consistent across clinically relevant subgroups. The median duration of response was 7.4 months. The median time to progression was 3.7 months. Median overall survival (OS) has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy.
Summary
In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile.
Keyword(s): Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 2
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:30 to 13.06.2015 12:45
Location: Room A2+3
Background
Novel agents including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs) have provided improved treatment outcomes for patients with multiple myeloma (MM). The majority of patients with MM still unfortunately relapse, with very limited options after PI and IMiD-based treatment. Daratumumab (DARA) is a human anti-CD38 IgG1κ mAb and has previously shown single agent activity and good tolerability in relapsed/refractory MM (Lokhorst HM et al. ASCO 2014).
Aims
This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and IMiD. Preliminary results are reported.
Methods
MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw for 8 weeks, q2w for 16 weeks, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC).
Results
Data for the 16 mg/kg DARA group are presented (n = 106). The median time from diagnosis was 4.8 years and patients received a median of 5 prior treatment lines. A total of 80% of patients received prior autologous stem cell transplants. Seventy five percent of patients were ISS stage 2 or higher. Ninety-six percent of patients were refractory to their last line of therapy and 95% were refractory to their last PI and IMiD. The proportions of patients refractory to other to agents included pomalidomide (63%), carfilzomib (48%) and alkylating agents (78%). Adverse events (AE; ≥20%) included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during the first infusion with 4.7% of patients with grade 3 IRRs. No grade 4 IRRs were reported and no patients discontinued the study due to IRRs. Five patients (4.7%) discontinued treatment due to AEs and none of these AEs were assessed by the investigator to be DARA-related. The ORR (IRC assessed) was 29.2%, with 3 stringent complete responses, 10 very good partial responses, and 18 partial responses. The ORR was consistent across clinically relevant subgroups. The median duration of response was 7.4 months. The median time to progression was 3.7 months. Median overall survival (OS) has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy.
Summary
In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile.
Keyword(s): Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 2
Abstract: S430
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:30 to 13.06.2015 12:45
Location: Room A2+3
Background
Novel agents including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs) have provided improved treatment outcomes for patients with multiple myeloma (MM). The majority of patients with MM still unfortunately relapse, with very limited options after PI and IMiD-based treatment. Daratumumab (DARA) is a human anti-CD38 IgG1κ mAb and has previously shown single agent activity and good tolerability in relapsed/refractory MM (Lokhorst HM et al. ASCO 2014).
Aims
This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and IMiD. Preliminary results are reported.
Methods
MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw for 8 weeks, q2w for 16 weeks, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC).
Results
Data for the 16 mg/kg DARA group are presented (n = 106). The median time from diagnosis was 4.8 years and patients received a median of 5 prior treatment lines. A total of 80% of patients received prior autologous stem cell transplants. Seventy five percent of patients were ISS stage 2 or higher. Ninety-six percent of patients were refractory to their last line of therapy and 95% were refractory to their last PI and IMiD. The proportions of patients refractory to other to agents included pomalidomide (63%), carfilzomib (48%) and alkylating agents (78%). Adverse events (AE; ≥20%) included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during the first infusion with 4.7% of patients with grade 3 IRRs. No grade 4 IRRs were reported and no patients discontinued the study due to IRRs. Five patients (4.7%) discontinued treatment due to AEs and none of these AEs were assessed by the investigator to be DARA-related. The ORR (IRC assessed) was 29.2%, with 3 stringent complete responses, 10 very good partial responses, and 18 partial responses. The ORR was consistent across clinically relevant subgroups. The median duration of response was 7.4 months. The median time to progression was 3.7 months. Median overall survival (OS) has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy.
Summary
In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile.
Keyword(s): Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 2
Type: Oral Presentation
Presentation during EHA20: From 13.06.2015 12:30 to 13.06.2015 12:45
Location: Room A2+3
Background
Novel agents including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs) have provided improved treatment outcomes for patients with multiple myeloma (MM). The majority of patients with MM still unfortunately relapse, with very limited options after PI and IMiD-based treatment. Daratumumab (DARA) is a human anti-CD38 IgG1κ mAb and has previously shown single agent activity and good tolerability in relapsed/refractory MM (Lokhorst HM et al. ASCO 2014).
Aims
This ongoing phase 2 study (NCT01985126) evaluated DARA monotherapy in the FDA breakthrough therapy designation population: MM patients with ≥3 prior lines of therapy including a PI and an IMiD, or double refractory to a PI and IMiD. Preliminary results are reported.
Methods
MMY2002 is a 2-part, open-label, international, multicenter study. In part 1 stage 1, 34 patients were randomized to DARA 8 mg/kg (n = 18) q4w or 16 mg/kg (n = 16) qw for 8 weeks, q2w for 16 weeks, then q4w in a Simon-2-stage design to determine the most effective dose. Subsequently, 90 additional patients were enrolled in the 16 mg/kg DARA group. The primary endpoint was overall response rate (ORR) by independent review (IRC).
Results
Data for the 16 mg/kg DARA group are presented (n = 106). The median time from diagnosis was 4.8 years and patients received a median of 5 prior treatment lines. A total of 80% of patients received prior autologous stem cell transplants. Seventy five percent of patients were ISS stage 2 or higher. Ninety-six percent of patients were refractory to their last line of therapy and 95% were refractory to their last PI and IMiD. The proportions of patients refractory to other to agents included pomalidomide (63%), carfilzomib (48%) and alkylating agents (78%). Adverse events (AE; ≥20%) included fatigue (39.6%), anemia (33.0%), nausea (29.2%), thrombocytopenia (25.5%), back pain (22.6%), neutropenia (22.6%), cough (20.8%). Infusion-related reactions (IRR, 42.5%) were mainly grade 1/2 during the first infusion with 4.7% of patients with grade 3 IRRs. No grade 4 IRRs were reported and no patients discontinued the study due to IRRs. Five patients (4.7%) discontinued treatment due to AEs and none of these AEs were assessed by the investigator to be DARA-related. The ORR (IRC assessed) was 29.2%, with 3 stringent complete responses, 10 very good partial responses, and 18 partial responses. The ORR was consistent across clinically relevant subgroups. The median duration of response was 7.4 months. The median time to progression was 3.7 months. Median overall survival (OS) has not been reached and the estimated 1-year OS rate is 65%. After a median follow up of 9.4 months 14/31 (45.2%) of responders remain on therapy.
Summary
In a heavily pre-treated MM population (95% refractory to last PI and IMiD), DARA at 16 mg/kg showed meaningful durable single agent activity, with deep responses and a favorable safety profile.
Keyword(s): Multiple myeloma
Session topic: Multiple myeloma: Clinical studies 2
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