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SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).
The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.
“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.
The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.
“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.
Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.
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Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.
Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.
IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.
Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.
Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.
Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.
Treatment with each agent was given at intravenous doses of 375 mg/m2 weekly for 4 weeks at days 1, 8, 15, and 22.
PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.
“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.
Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.
The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.
SOURCE: Sharman J et al. ASH 2018: Abstract 394.
SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).
The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.
“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.
The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.
“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.
Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.
[embed:render:related:node:189761]
Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.
Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.
IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.
Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.
Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.
Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.
Treatment with each agent was given at intravenous doses of 375 mg/m2 weekly for 4 weeks at days 1, 8, 15, and 22.
PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.
“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.
Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.
The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.
SOURCE: Sharman J et al. ASH 2018: Abstract 394.
SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).
The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.
“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.
The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.
“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.
Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.
[embed:render:related:node:189761]
Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.
Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.
IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.
Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.
Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.
Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.
Treatment with each agent was given at intravenous doses of 375 mg/m2 weekly for 4 weeks at days 1, 8, 15, and 22.
PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.
“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.
Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.
The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.
SOURCE: Sharman J et al. ASH 2018: Abstract 394.
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All rights reserved. This material may not be published, broadcast, copied, or otherwise reproduced or distributed without the prior written permission of Frontline Medical Communications Inc.</copyrightNotice> </rightsInfo> </provider> <abstract/> <metaDescription>SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those</metaDescription> <articlePDF/> <teaserImage>236700</teaserImage> <teaser>PF-05280586 showed biosimilarity to rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive LTB-FL.</teaser> <title>Phase 3 study confirms biosimilarity of PF-05280586 with rituximab</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear/> <pubPubdateMonth/> <pubPubdateDay/> <pubVolume/> <pubNumber/> <wireChannels/> <primaryCMSID/> <CMSIDs/> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>HemN</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle/> <journalFullTitle/> <copyrightStatement/> </publicationData> <publicationData> <publicationCode>oncr</publicationCode> <pubIssueName/> <pubArticleType/> <pubTopics/> <pubCategories/> <pubSections/> </publicationData> </publications_g> <publications> <term>18</term> <term canonical="true">31</term> </publications> <sections> <term canonical="true">53</term> <term>39313</term> </sections> <topics> <term canonical="true">242</term> <term>278</term> <term>178</term> </topics> <links> <link> <itemClass qcode="ninat:picture"/> <altRep contenttype="image/jpeg">images/2400b1db.jpg</altRep> <description role="drol:caption">Dr. Jeff Sharman</description> <description role="drol:credit">Sharon Worcester/MDedge News</description> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Phase 3 study confirms biosimilarity of PF-05280586 with rituximab</title> <deck/> </itemMeta> <itemContent> <p><span class="dateline">SAN DIEGO </span>– The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).[[{"fid":"236700","view_mode":"medstat_image_flush_left","fields":{"format":"medstat_image_flush_left","field_file_image_alt_text[und][0][value]":"Dr. Jeff Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.","field_file_image_credit[und][0][value]":"Sharon Worcester/MDedge News","field_file_image_caption[und][0][value]":"Dr. Jeff Sharman"},"type":"media","attributes":{"class":"media-element file-medstat_image_flush_left"}}]]</p> <p>The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the <span class="Hyperlink"><a href="http://www.hematology.org/Annual-Meeting/">annual meeting</a></span> of the American Society of Hematology.<br/><br/>“This resulted in a difference between the two arms of 4.66%,” said <span class="Hyperlink"><a href="https://oregoncancer.com/providers/jeff-sharman-md/">Dr. Sharman</a></span> of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.<br/><br/>The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.<br/><br/>“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.<br/><br/>Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.<br/><br/>Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.<br/><br/>Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.<br/><br/>IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.<br/><br/>Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.<br/><br/>Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging. <br/><br/>Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.<br/><br/>Treatment with each agent was given at intravenous doses of 375 mg/m<sup>2</sup> weekly for 4 weeks at days 1, 8, 15, and 22.<br/><br/>PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.<br/><br/>“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.<br/><br/>Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration <span class="Hyperlink"><a href="https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm627009.htm">approval</a></span> of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.<br/><br/>The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.<br/><br/><b/></p> <p><span class="Primary">SOURCE:</span> Sharman J et al. ASH 2018: <span class="Hyperlink"><a href="https://ash.confex.com/ash/2018/webprogram/Paper111248.html">Abstract 394</a></span>.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>teaser</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>vitals</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p><strong>Key clinical point: </strong>PF-05280586 shows biosimilarity to rituximab at up to 26 weeks.<br/><br/><strong>Major finding: </strong>ORR at 26 weeks was 75.5% vs. 70.7% with PF-05280586 vs. rituximab, respectively.<br/><br/><strong>Study details:</strong> A phase 3 study of 394 patients. <br/><br/><strong>Disclosures:</strong> This study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech. <br/><br/><strong>Source: </strong>Sharman J et al. ASH 2018: Abstract 394.</p> </itemContent> </newsItem> </itemSet></root>
REPORTING FROM ASH 2018
Key clinical point: PF-05280586 shows biosimilarity to rituximab at up to 26 weeks.
Major finding: ORR at 26 weeks was 75.5% vs. 70.7% with PF-05280586 vs. rituximab, respectively.
Study details: A phase 3 study of 394 patients.
Disclosures: This study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.
Source: Sharman J et al. ASH 2018: Abstract 394.
