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The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).
BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.
In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.
The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Phase 3 trial
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
Phase 2 trials
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.
The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.
Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.
Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.
The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).
The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.
Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.
Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).
The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).
Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1). 
The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).
BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.
In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.
The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Phase 3 trial
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
Phase 2 trials
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.
The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.
Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.
Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.
The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).
The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.
Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.
Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).
The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).
Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).
The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).
BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.
In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.
The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.
Phase 3 trial
Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.
There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.
The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.
The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).
For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.
Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).
For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.
Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).
For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.
The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).
Phase 2 trials
Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.
The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.
Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.
Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.
The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).
The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.
Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.
Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).
The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).
Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).