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with 3.6 months in those receiving best supportive care ( p values not reported ). In the second monotherapy trial , which was a single-arm study of 57 patients with relapsed CD33-positive AML , 26 percent of patients achieved a complete remission that lasted a median of 11.6 months ( range not provided ) after receiving a single course of GO .
The most common AEs associated with GO included pyrexia , nausea , infection , vomiting , bleeding , thrombocytopenia , stomatitis , constipation , rash , headache , elevated liver function tests , and neutropenia . Severe AEs included leukopenia , infection , liver damage , hepatic veno-occlusive disease , infusion-related reactions ( IRRs ), and hemorrhage .
GO previously received orphan-drug designation and carries a boxed warning that severe or fatal hepatotoxicity , including veno-occlusive disease and sinusoidal obstruction syndrome , has occurred in some patients .
Source : U . S . Food and Drug Administration press release , September 1 , 2017 .
Obinutuzumab Receives Priority Review for Follicular Lymphoma The FDA granted priority review to the anti-CD20 monoclonal antibody obinutuzumab in combination with chemotherapy , followed by obinutuzumab alone , for the treatment of follicular lymphoma ( FL ).
The decision was based on results from the international , phase III GALLIUM study , which included 1,401 treatmentnaïve patients with indolent non-Hodgkin lymphoma ( NHL ; 1,202 of whom had FL ) who were randomized to receive frontline obinutuzumab ( 1,000 mg on days 1 , 8 , and 15 of cycle 1 and day 1 of subsequent cycles ) plus chemotherapy ( n = 601 ) or rituximab ( 375 mg / m 2 on day 1 of each cycle ) plus chemotherapy ( n = 601 ). The chemotherapy regimen was either CHOP , CVP ( cyclophosphamide , vincristine , prednisone ), or bendamustine , depending on physician ’ s choice .
At median follow-up of 41.1 months ( range not provided ), the median PFS ( primary endpoint ) had not been reached in either treatment cohort . The risk of disease progression or death was reduced by 32 percent in patients treated with obinutuzumab , compared with rituximab ( HR = 0.68 ; 95 % CI 0.54-0.837 ; p = 0.0016 ). The HR for OS was 0.75 ( 95 % CI 0.49-1.17 ; p = 0.21 ).
At 34.5 months of follow-up ( range not provided ), the three-year PFS rate was 80 percent in the obinutuzumab cohort and 73.3 percent in the rituximab group , and the three-year OS rate was 94 percent and 92.1 percent , respectively . The ORR was
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88.5 percent in the obinutuzumab group and 86.9 percent in the rituximab group . Rates of complete and partial remissions were similar between the obinutuzumab and rituximab groups ( 19.5 % and 23.8 %; 69.1 % and 63.1 %, respectively ; p values not reported ).
More patients in the obinutuzumab group achieved minimal residual disease negativity ( 92 % vs . 84.9 %; p = 0.0041 ).
The most common grade 3-5 AEs that occurred more often in the obinutuzumab cohort were neutropenia ( 46.7 % vs . 39.5 %), infections ( 20.3 % vs . 16.4 %), IRRs ( 12.4 % vs . 6.7 %), thrombocytopenia ( 6.1 % vs . 2.7 %), second malignancies ( 4.7 % vs . 2.7 %), and cardiac events ( 3.9 % vs . 2.8 %).
The FDA ’ s decision is expected on or before December 23 , 2017 . Obinutuzumab was previously approved for use in combination with bendamustine for patients with previously treated FL .
Source : Genentech press release , August 27 , 2017 .
FDA Accepts Application for Rituximab Biosimilar for Several Indications The FDA accepted a biologics license application for the rituximab biosimilar GP2013 for the treatment of FL , DLBCL , and CLL . The decision was based on results from the ASSIST-FL trial , which compared the safety , efficacy , and pharmacokinetics of GP2013 and rituximab .
The multinational , double-blind , randomized , controlled , confirmatory , phase III study enrolled 629 patients with untreated , advanced FL who were randomized 1:1 to receive eight cycles of GP2013 ( n = 314 ) or rituximab ( n = 315 ) in combination with CVP over 24 weeks .
GP2013 demonstrated similar efficacy to rituximab , with ORRs ( primary endpoint ) of 87 percent and 88 percent , respectively , for a between-group difference of -0.4 percent ( 95 % CI -5.94-5.14 ; p value not provided ). At the end of the combination phase , 55 patients in the GP2013 group and 59 patients in the rituximab group achieved CR , for a between-group difference of -1.1 percent ( 90 % CI -7.46-5.25 ; p value not provided ). The difference in CR between groups was 2.3 percent ( 90 % CI -8-3.29 ) at 15 months , 0.6 percent ( 90 % CI -5.59-6.75 ) at 27 months , and 0.4 percent ( 90 % CI -6.61-5.88 ) at 33 months ( p values not provided ).
At data cutoff ( median follow-up = 23.8 months ; range not provided ), the median PFS and OS had not been reached in either cohort ; 30 percent of patients in the GP2013 cohort and 24 percent in the rituximab cohort had experienced a PFS event ( HR = 1.31 ; 95 % CI 0.97-1.78 ). However , the study was not powered to show similarity in
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PFS and OS , the researchers cautioned .
Treatment was discontinued early in both groups ( n = 10 in each ) because of disease progression . Rates of dose modifications ( 5 % in each group ) and dose delays or interruptions ( 41 % in each group ) were similar ( p values not provided ). Twentythree patients ( 7 %) in the GP2013 group and 29 patients ( 9 %) in the rituximab group died ( HR = 0.77 ; 95 % CI 0.45-1.33 ; p value not provided ).
AEs occurring in the GP2013 and rituximab groups were similar : 93 percent and 91 percent , respectively , experienced any-grade AEs ; 23 percent and 20 percent , respectively , experienced serious AEs ( p values not provided ). The most common AEs were neutropenia ( 26 % and 30 %), constipation ( 22 % and 20 %), and nausea ( 16 % and 13 %), and the most common grade 3 / 4 event was neutropenia ( 18 % and 21 %).
Five patients in the GP2013 group and three in the rituximab group developed anti-drug antibodies .
GP2013 has demonstrated an identical amino acid sequence , matched protein structures and modifications , and indistinguishable biological and functional properties . The clinical pharmacokinetic profile of GP2013 appears similar to rituximab .
Sources : Sandoz press release , September 12 , 2017 ; Jurczak W , Illidia M , Govindbaby KS , et al . A phase III efficacy and safety study of the proposed rituximab biosimilar GP2013 versus rituximab in patients with previously untreated advanced follicular lymphoma . Abstract # 128 . Presented at the 2016 ASH Annual Meeting , December 3 , 2016 ; San Diego , CA .
FDA Grants Accelerated Approval to Copanlisib for Relapsed FL The FDA granted accelerated approval for copanlisib for adults with relapsed FL who have received at least two prior systemic therapies . This is the first approval of an intravenous phosphatidylinositol 3-kinase inhibitor .
The approval was based on results from the single-arm , phase II CHRONOS-1 study , which included 104 patients with follicular B-cell NHL who had relapsed after at least two prior treatments . Patients received copanlisib 60 mg intravenously on days one , eight , and 15 of a 28-day cycle .
Sixty-one patients responded to copanlisib treatment , for an ORR of 59 percent ( primary endpoint ; 95 % CI 49- 68 ), with 15 patients ( 14 %) achieving a CR for a median duration of 12.2 months ( range = 0-22.6 months ).
The most common AEs included hyperglycemia ( 54 %), leukopenia ( 36 %), diarrhea ( 36 %), decreased general strength and energy ( 36 %), hypertension ( 35 %), neutropenia ( 32 %), nausea ( 26 %), thrombocytopenia ( 22 %), and lower respiratory tract infections ( 21 %). Serious AEs occurred in 44 patients ( 26 %) and included infections , hyperglycemia , hypertension , non-infectious pneumonitis , neutropenia , and severe skin reactions . AEs led to dose
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reductions in 36 patients ( 21 %) and discontinuations in 27 patients ( 16 %).
Copanlisib was previously granted priority review and orphan-drug designation .
Sources : U . S . Food and Drug Administration press release , September 14 , 2017 ; Bayer press release , September 14 , 2017 .
First CAR T-Cell Therapy for B-Cell Lymphoma Receives FDA Approval The FDA approved the chimeric antigen receptor ( CAR ) T-cell therapy axicabtagene ciloleucel ( or KTE-C19 ) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of therapy , including DLBCL not otherwise specified , primary mediastinal large B-cell lymphoma ( PMBCL ), highgrade B-cell lymphoma , and DLBCL arising from FL .
The safety and efficacy of axicabtagene ciloleucel were demonstrated in the ZUMA-1 trial , which included 111 patients ( median age = 58 years ; range = 23-76 years ) with previously treated DLBCL , PMBCL , or transformed FL from 22 institutions . As of the data cutoff date ( January 27 , 2017 ), 101 patients ( 91 %) had received axicabtagene ciloleucel 2 × 10 6 cells / kg , following conditioning with low-dose cytarabine and fludarabine . The ORR as assessed by independent central review was 72 percent , with a CR rate of 51 percent ( 95 % CI 41-62 ). The median duration of response was 8.1 months ( range not provided ) and was not reached for patients who achieved CR . The median OS also was not reached during study follow-up , and the sixmonth OS rate was 80 percent .
The most common grade ≥3 treatmentrelated AEs included neutropenia ( 66 %), leukopenia ( 44 %), anemia ( 43 %), febrile neutropenia ( 31 %), thrombocytopenia , ( 24 %), and encephalopathy ( 21 %).
The drug carries a boxed warning for cytokine release syndrome ( CRS ) and neurologic events and was approved with a Risk Evaluation and Mitigation Strategy . In the study , 13 percent and 28 percent of patients experienced severe , grade ≥3 CRS and neurologic events , respectively . Fatal cases of CRS and neurologic toxicity occurred .
In the subset of 70 patients who experienced CRS or neurologic events , 43 required treatment with tocilizumab and 27 required treatment with tocilizumab and steroids , but these treatments did not decrease the efficacy of axicabtagene ciloleucel ( ORR = 84 % and 78 %, respectively ). ●
Sources : U . S . Food and Drug Administration news release , October 18 , 2017 ; Kite Pharma news release , October 18 , 2017 .
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