The Experts below are selected from a list of 57 Experts worldwide ranked by ideXlab platform
George Peoples - One of the best experts on this subject based on the ideXlab platform.
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efficacy and Safety analySiS of Nelipepimut S vaccine to prevent breaSt cancer recurrence a randomized multicenter phaSe iii clinical trial
Clinical Cancer Research, 2019Co-Authors: Elizabeth A Mittendorf, Michelle E Melisko, Katarina Petrakova, Biao Lu, Julie Price A Hiller, Igor Bondarenko, A M Brunt, Grybach Sergii, George PeoplesAbstract:PurpoSe: In phaSe I/II StudieS, Nelipepimut-S (NP-S) pluS GM-CSF vaccine waS well tolerated and effectively raiSed HER2-Specific immunity in patientS with breaSt cancer. ReSultS from a preSpecified interim analySiS of a phaSe III trial aSSeSSing NP-S + GM-CSF are reported. PatientS and MethodS: ThiS multicenter, randomized, double-blind phaSe III Study enrolled femaleS ≥18 yearS with T1–T3, HER2 low–expreSSing (IHC 1+/2+), node-poSitive breaSt cancer in the adjuvant Setting. PatientS received 1,000 μg NP-S + 250 μg GM-CSF or placebo + GM-CSF monthly for 6 monthS, then every 6 monthS through 36 monthS. The primary objective waS diSeaSe-free Survival (DFS). Protocol-Specified imaging occurred annually. New abnormalitieS were categorized aS recurrence eventS; biopSy confirmation waS not mandated. The interim analySiS waS conducted aS Specified in the protocol after 73 DFS eventS. ReSultS: A total of 758 patientS (mean age 51.8 yearS) were randomized. AdverSe eventS were Similar between groupS; moSt common were injection-aSSociated: erythema (84.3%), induration (55.8%), and prurituS (54.9%). There waS no Significant between-armS difference in DFS eventS at interim analySiS at median follow-up (16.8 monthS). In the NP-S arm, imaging detected 54.1% of recurrence eventS in aSymptomatic patientS verSuS 29.2% in the placebo arm (P = 0.069). ConcluSionS: NP-S waS well tolerated. There waS no Significant difference in DFS eventS between NP-S and placebo. USe of mandated annual ScanS and image-detected recurrence eventS haStened the interim analySiS contributing to early trial termination.
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initial Safety analySiS of a randomized phaSe ii trial of Nelipepimut S gm cSf and traStuzumab compared to traStuzumab alone to prevent recurrence in breaSt cancer patientS with her2 low expreSSing tumorS
Clinical Immunology, 2019Co-Authors: Travis G Clifton, Timothy J Vreeland, Diane F Hale, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Lukas, Garth S Herbert, George PeoplesAbstract:AbStract The development of HER2-targeted therapy haS decreaSed recurrence rateS and improved Survival, tranSforming the natural hiStory of HER2-poSitive breaSt cancer. However only a minority of breaSt cancer patientS benefit aS theSe agentS are not uSed in patientS with tumorS expreSSing low levelS of HER2. Preclinical data SuggeStS a SynergiStic action of HER2-targeted vaccination with traStuzumab. We report the initial Safety interim analySiS of a phaSe II trial that enrolled patientS with HER2 low-expreSSing (IHC 1+/2+) breaSt cancer who were clinically diSeaSe-free after Standard therapy. PatientS were randomized to receive the HER2-peptide vaccine Nelipepimut-S + GM-CSF with traStuzumab (vaccine arm) or traStuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analySiS that occurred after enrollment of 150 patientS Showed no Significant differenceS in toxicity between the two armS, including cardiac toxicity. The clinical efficacy of thiS combination will be reported 6 monthS after the final patient waS enrolled.
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Initial Safety analySiS of a randomized phaSe II trial of Nelipepimut-S + GM-CSF and traStuzumab compared to traStuzumab alone to prevent recurrence in breaSt cancer patientS with HER2 low-expreSSing tumorS
Clinical Immunology, 2019Co-Authors: G. Travis Clifton, Timothy J Vreeland, Diane F Hale, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Lukas, Garth S Herbert, George PeoplesAbstract:AbStract The development of HER2-targeted therapy haS decreaSed recurrence rateS and improved Survival, tranSforming the natural hiStory of HER2-poSitive breaSt cancer. However only a minority of breaSt cancer patientS benefit aS theSe agentS are not uSed in patientS with tumorS expreSSing low levelS of HER2. Preclinical data SuggeStS a SynergiStic action of HER2-targeted vaccination with traStuzumab. We report the initial Safety interim analySiS of a phaSe II trial that enrolled patientS with HER2 low-expreSSing (IHC 1+/2+) breaSt cancer who were clinically diSeaSe-free after Standard therapy. PatientS were randomized to receive the HER2-peptide vaccine Nelipepimut-S + GM-CSF with traStuzumab (vaccine arm) or traStuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analySiS that occurred after enrollment of 150 patientS Showed no Significant differenceS in toxicity between the two armS, including cardiac toxicity. The clinical efficacy of thiS combination will be reported 6 monthS after the final patient waS enrolled.
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The development and uSe of the E75 (HER2 369–377) peptide vaccine
Future Oncology, 2016Co-Authors: Guy T Clifton, George Peoples, Elizabeth A MittendorfAbstract:E75 (Nelipepimut-S) iS an immunogenic peptide derived from the HER2 protein. When combined with the immunoadjuvant granulocyte–macrophage colony-Stimulating factor (GM-CSF), Nelipepimut-S haS been uSed aS a vaccine that iS capable of eliciting a robuSt anti-HER2 immune reSponSe. Early-phaSe clinical trialS that enrolled women with node-poSitive or high-riSk node-negative breaSt cancer who had been rendered diSeaSe free with Standard of care therapy but were at riSk for recurrence, demonStrated the vaccine to be Safe with a SuggeStion of clinical benefit. Nelipepimut-S iS currently being evaluated in a PhaSe III clinical trial. ThiS article coverS the preclinical and clinical development of Nelipepimut-S.
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abStract ot3 1 09 combination immunotherapy with traStuzumab and the her2 vaccine e75 Nelipepimut S in high riSk her2 breaSt cancer patientS to prevent recurrence
Cancer Research, 2015Co-Authors: Beth Mittendorf, John S Berry, Alfred F Trappey, Guy T Clifton, Sathibalan Ponniah, Erika J Schneble, Jarrod P Holmes, Nuhad K Ibrahim, Julia M Greene, George PeoplesAbstract:Background: In an adjuvant phaSe II trial, the HER2-derived Nelipepimut-S (E75) + GM-CSF vaccine (Neuvax) haS been Shown to reduce breaSt cancer recurrence. Preclinical teSting of the combination of traStuzumab (Tz) and Nelipepimut-S haS Shown SynergiStic cytolySiS againSt HER2 expreSSing cancer cellS. In pilot phaSe II data in HER2+ patientS (ptS), 55 ptS doSed with CD8-eliciting HER2 derived peptide vaccineS Sequentially after treatment with Tz reSulted in no recurrenceS at 36 monthS median follow-up compared with a 16% recurrence rate in 34 randomized controlS treated with Tz without vaccine (p=.012). BaSed on theSe data, we have deSigned a trial to evaluate the ability of the combination of Tz and the E75 vaccine concurrently to prevent recurrence in ptS with high-riSk, HER2+ breaSt cancer. Trial DeSign: ThiS Study will be a multicenter, proSpective, randomized, Single-blinded, phaSe II trial evaluating adjuvant Tz + NeuVax (E75+GM-CSF) vS. Tz + GM-CSF alone in high-riSk HER2+ (IHC 3+ and/or FISH >2.2) breaSt cancer ptS. High-riSk ptS include: 1) thoSe that did not achieve a pathologic complete reSponSe (pCR) after neoadjuvant chemotherapy and HER2- targeted therapy or 2) thoSe treated with upfront Surgery that are node poSitive (> 4+ LN or 1-3+ LN if hormone receptor negative). PtS muSt be HLA-A2 /A3+ to be eligible (E75 iS HLA-A2/A3-reStricted) with ECOG performance StatuS 0-1. PtS will be enrolled after completing Standard of care multi-modal therapy but prior to the 3rd doSe of Tz maintenance therapy (monotherapy). PtS will be randomized 1:1 to receive either NeuVax or GM-CSF alone which will be adminiStered aS Six monthly intradermal inoculationS concurrently with Tz therapy. PtS will then receive four booSter inoculationS of either NeuVax or GM-CSF every 6 monthS. The primary efficacy endpoint iS to compare diSeaSe-free Survival (DFS) between treatment armS. Secondary objectiveS will include evaluation of local and SyStemic toxicity, diStant recurrence free Survival, and in vivo/in vitro immunologic reSponSeS. From previouSly publiShed experience with Tz, we expect a recurrence rate of 20% in Tz (pluS GM-CSF) treated ptS and anticipate that the combination of Tz with E75+GM-CSF will reduce thiS recurrence rate to 5%. In order to Show StatiStical difference between theSe recurrence rateS, we plan to enroll 50 ptS per treatment arm (100 total) with a type I error rate of 5% and 80% power to detect the primary endpoint. Trial accrual iS anticipated to begin in September of 2014, with a two year period for trial enrollment followed by a three year follow-up period. ConcluSion: We hypotheSize that combination adjuvant immunotherapy with Tz and NeuVax will reSult in a greater reduction in breaSt cancer recurrence than Tz therapy alone. We have deSigned a proSpective, randomized, Single-blinded, phaSe II trial evaluating the efficacy of thiS immunotherapy combination in high-riSk HER2+ breaSt cancer ptS to teSt thiS hypotheSiS. Contact Information: ThiS trial iS funded by a DoD grant to EAM with matching fundS from Galena Biopharma and iS being conducted with the aSSiStance of the academic CRO, Cancer InCITe, LLC. Citation Format: Beth A Mittendorf, Erika J Schneble, Nuhad K Ibrahim, Julia M Greene, John S Berry, Alfred F Trappey, Guy T Clifton, Jarrod P HolmeS, Sathibalan Ponniah, George E PeopleS. Combination immunotherapy with traStuzumab and the HER2 vaccine E75 (Nelipepimut-S) in high-riSk HER2+ breaSt cancer patientS to prevent recurrence [abStract]. In: ProceedingS of the Thirty-Seventh Annual CTRC-AACR San Antonio BreaSt Cancer SympoSium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer ReS 2015;75(9 Suppl):AbStract nr OT3-1-09.
Elizabeth A Mittendorf - One of the best experts on this subject based on the ideXlab platform.
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efficacy and Safety analySiS of Nelipepimut S vaccine to prevent breaSt cancer recurrence a randomized multicenter phaSe iii clinical trial
Clinical Cancer Research, 2019Co-Authors: Elizabeth A Mittendorf, Michelle E Melisko, Katarina Petrakova, Biao Lu, Julie Price A Hiller, Igor Bondarenko, A M Brunt, Grybach Sergii, George PeoplesAbstract:PurpoSe: In phaSe I/II StudieS, Nelipepimut-S (NP-S) pluS GM-CSF vaccine waS well tolerated and effectively raiSed HER2-Specific immunity in patientS with breaSt cancer. ReSultS from a preSpecified interim analySiS of a phaSe III trial aSSeSSing NP-S + GM-CSF are reported. PatientS and MethodS: ThiS multicenter, randomized, double-blind phaSe III Study enrolled femaleS ≥18 yearS with T1–T3, HER2 low–expreSSing (IHC 1+/2+), node-poSitive breaSt cancer in the adjuvant Setting. PatientS received 1,000 μg NP-S + 250 μg GM-CSF or placebo + GM-CSF monthly for 6 monthS, then every 6 monthS through 36 monthS. The primary objective waS diSeaSe-free Survival (DFS). Protocol-Specified imaging occurred annually. New abnormalitieS were categorized aS recurrence eventS; biopSy confirmation waS not mandated. The interim analySiS waS conducted aS Specified in the protocol after 73 DFS eventS. ReSultS: A total of 758 patientS (mean age 51.8 yearS) were randomized. AdverSe eventS were Similar between groupS; moSt common were injection-aSSociated: erythema (84.3%), induration (55.8%), and prurituS (54.9%). There waS no Significant between-armS difference in DFS eventS at interim analySiS at median follow-up (16.8 monthS). In the NP-S arm, imaging detected 54.1% of recurrence eventS in aSymptomatic patientS verSuS 29.2% in the placebo arm (P = 0.069). ConcluSionS: NP-S waS well tolerated. There waS no Significant difference in DFS eventS between NP-S and placebo. USe of mandated annual ScanS and image-detected recurrence eventS haStened the interim analySiS contributing to early trial termination.
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final analySiS of Nelipepimut S pluS gm cSf with traStuzumab verSuS traStuzumab alone to prevent recurrenceS in high riSk her2 low expreSSing breaSt cancer a proSpective randomized blinded multicenter phaSe iib trial
Journal of Clinical Oncology, 2019Co-Authors: Annelies Hickerson, Timothy J Vreeland, Diane F Hale, Travis G Clifton, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:1Background: Preclinical data ShowS SynergiSm between traStuzumab (Tz) and HER2-targeted vaccineS. We evaluated adjvuant Nelipepimut-S (NPS) + GM-CSF with Tz compared to Tz with GM-CSF alone in HER...
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immunologic reSponSeS in triple negative breaSt cancer patientS in a randomized phaSe iib trial of Nelipepimut S pluS traStuzumab verSuS traStuzumab alone to prevent recurrence
Journal of Clinical Oncology, 2019Co-Authors: Jessica Campf, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Annelies Hickerson, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:556Background: BreaSt cancer (BC) patientS (ptS) expreSSing low levelS of HER2 by (immunohiStochemiStry (IHC) 1-2+) are not eligible for traStuzumab (Tz). However, in a randomized phaSe 2b trial, t...
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abStract ot3 01 04 vadiS trial phaSe ii trial of the Nelipepimut S peptide vaccine in women with dciS of the breaSt
Cancer Research, 2017Co-Authors: Elizabeth A Mittendorf, G Plitas, Judy Garber, Katherine D Crew, Brandy M Heckmanstoddard, M Wojtowicz, Lana Vornik, G E Peoples, P H BrownAbstract:Background: Our group haS been inveStigating vaccination StrategieS in breaSt cancer. Specifically, we have been evaluating HER2-derived peptide vaccineS including Nelipepimut-S+GM-CSF adminiStered adjuvantly to breaSt cancer patientS who have been rendered diSeaSe-free with Standard of care therapy but are at high riSk for recurrence. Early phaSe clinical trialS Showed an approximately 50% reduction in relative recurrence riSk in vaccinated patientS. BaSed on theSe data, Nelipepimut-S+GM-CSF iS being evaluated in a phaSe III regiStration trial. Having Shown the vaccine to be Safe, effective in Stimulating an antigen-Specific immune reSponSe and potentially having clinical efficacy in the Setting of Secondary prevention, the current Study waS initiated to evaluate vaccination in DCIS patientS. ThiS trial repreSentS an initial Step to move the vaccine into the primary prevention Setting. Trial DeSign: PhaSe II, randomized, Single-blind Study. PatientS will be randomized 2:1 to receive vaccine or GM-CSF alone. After enrollment, patientS will receive 3 inoculationS adminiStered every other week preoperatively followed by Surgery then completion of the vaccination SerieS (3 additional inoculationS) in the adjuvant Setting. Eligibility: The trial will enroll pre- or poSt-menopauSal women with a diagnoSiS of DCIS made by core biopSy. The area of radiographic abnormality muSt meaSure at leaSt 1 cm. BecauSe the vaccine iS a MHC claSS I, CD8+ T cell-eliciting vaccine, it iS HLA reStricted, and patientS muSt be HLA-A2+ to enroll. ParticipantS muSt alSo have an ECOG performance StatuS Specific AimS: The trial9S primary endpoint iS to evaluate for Nelipepimut-Specific CD8+ T cellS in the peripheral blood of vaccinated patientS compared to patientS receiving GM-CSF alone. Secondary endpointS include evaluating toxicity; determining the immune reSponSe in vivo by DTH, in vitro by evaluating for epitope Spreading to other tumor antigenS, and importantly in the tumor by aSSeSSing the degree of lymphocytic infiltration in Surgically reSected SpecimenS. The extent of HER2 expreSSion, Ki67 and cleaved caSpaSe 3 in the reSected Specimen will alSo be aSSeSSed. StatiStical MethodS: A total of 108 DCIS patientS will be conSented and Screened for eligibility. 48 (45%) are expected to be HLA-A2 poSitive. TheSe 48 patienSt will be randomized 2:1 to vaccine or GM-CSF alone groupS. Accounting for 10% attrition rate and for an approximately 5% non-evaluable Sample rate, we expect to have 40 evaluable patientS, 27 in the vaccine group and 13 in the GM-CSF alone group, that have baSeline, pre-Surgery, and poSt-Surgery meaSureS of Nelipepimut-S-Specific CD8+ T cellS. We will have 82% power to detect a Significant increaSe in Nelipepimut-S-Specific CD8+ T cellS in the vaccine group verSuS the GM-CSF alone group. Contact Info: The Study iS accruing at four SiteS to include Columbia UniverSity, Dana Farber Cancer InStitute, MD AnderSon Cancer Center and Memorial Sloan Kettering Cancer Center. Additional information can be obtained from the overall Study PI, Dr. Elizabeth Mittendorf (eamitten@mdanderSon.org). NCT0236582. Citation Format: Mittendorf EA, PlitaS G, Garber J, Crew K, Heckman-Stoddard B, Wojtowicz M, Vornik L, PeopleS GE, Brown PH. VADIS trial: PhaSe II trial of the Nelipepimut-S peptide vaccine in women with DCIS of the breaSt [abStract]. In: ProceedingS of the 2016 San Antonio BreaSt Cancer SympoSium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer ReS 2017;77(4 Suppl):AbStract nr OT3-01-04.
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The development and uSe of the E75 (HER2 369–377) peptide vaccine
Future Oncology, 2016Co-Authors: Guy T Clifton, George Peoples, Elizabeth A MittendorfAbstract:E75 (Nelipepimut-S) iS an immunogenic peptide derived from the HER2 protein. When combined with the immunoadjuvant granulocyte–macrophage colony-Stimulating factor (GM-CSF), Nelipepimut-S haS been uSed aS a vaccine that iS capable of eliciting a robuSt anti-HER2 immune reSponSe. Early-phaSe clinical trialS that enrolled women with node-poSitive or high-riSk node-negative breaSt cancer who had been rendered diSeaSe free with Standard of care therapy but were at riSk for recurrence, demonStrated the vaccine to be Safe with a SuggeStion of clinical benefit. Nelipepimut-S iS currently being evaluated in a PhaSe III clinical trial. ThiS article coverS the preclinical and clinical development of Nelipepimut-S.
Guy T Clifton - One of the best experts on this subject based on the ideXlab platform.
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immunologic reSponSeS in triple negative breaSt cancer patientS in a randomized phaSe iib trial of Nelipepimut S pluS traStuzumab verSuS traStuzumab alone to prevent recurrence
Journal of Clinical Oncology, 2019Co-Authors: Jessica Campf, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Annelies Hickerson, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:556Background: BreaSt cancer (BC) patientS (ptS) expreSSing low levelS of HER2 by (immunohiStochemiStry (IHC) 1-2+) are not eligible for traStuzumab (Tz). However, in a randomized phaSe 2b trial, t...
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The development and uSe of the E75 (HER2 369–377) peptide vaccine
Future Oncology, 2016Co-Authors: Guy T Clifton, George Peoples, Elizabeth A MittendorfAbstract:E75 (Nelipepimut-S) iS an immunogenic peptide derived from the HER2 protein. When combined with the immunoadjuvant granulocyte–macrophage colony-Stimulating factor (GM-CSF), Nelipepimut-S haS been uSed aS a vaccine that iS capable of eliciting a robuSt anti-HER2 immune reSponSe. Early-phaSe clinical trialS that enrolled women with node-poSitive or high-riSk node-negative breaSt cancer who had been rendered diSeaSe free with Standard of care therapy but were at riSk for recurrence, demonStrated the vaccine to be Safe with a SuggeStion of clinical benefit. Nelipepimut-S iS currently being evaluated in a PhaSe III clinical trial. ThiS article coverS the preclinical and clinical development of Nelipepimut-S.
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abStract ot3 1 09 combination immunotherapy with traStuzumab and the her2 vaccine e75 Nelipepimut S in high riSk her2 breaSt cancer patientS to prevent recurrence
Cancer Research, 2015Co-Authors: Beth Mittendorf, John S Berry, Alfred F Trappey, Guy T Clifton, Sathibalan Ponniah, Erika J Schneble, Jarrod P Holmes, Nuhad K Ibrahim, Julia M Greene, George PeoplesAbstract:Background: In an adjuvant phaSe II trial, the HER2-derived Nelipepimut-S (E75) + GM-CSF vaccine (Neuvax) haS been Shown to reduce breaSt cancer recurrence. Preclinical teSting of the combination of traStuzumab (Tz) and Nelipepimut-S haS Shown SynergiStic cytolySiS againSt HER2 expreSSing cancer cellS. In pilot phaSe II data in HER2+ patientS (ptS), 55 ptS doSed with CD8-eliciting HER2 derived peptide vaccineS Sequentially after treatment with Tz reSulted in no recurrenceS at 36 monthS median follow-up compared with a 16% recurrence rate in 34 randomized controlS treated with Tz without vaccine (p=.012). BaSed on theSe data, we have deSigned a trial to evaluate the ability of the combination of Tz and the E75 vaccine concurrently to prevent recurrence in ptS with high-riSk, HER2+ breaSt cancer. Trial DeSign: ThiS Study will be a multicenter, proSpective, randomized, Single-blinded, phaSe II trial evaluating adjuvant Tz + NeuVax (E75+GM-CSF) vS. Tz + GM-CSF alone in high-riSk HER2+ (IHC 3+ and/or FISH >2.2) breaSt cancer ptS. High-riSk ptS include: 1) thoSe that did not achieve a pathologic complete reSponSe (pCR) after neoadjuvant chemotherapy and HER2- targeted therapy or 2) thoSe treated with upfront Surgery that are node poSitive (> 4+ LN or 1-3+ LN if hormone receptor negative). PtS muSt be HLA-A2 /A3+ to be eligible (E75 iS HLA-A2/A3-reStricted) with ECOG performance StatuS 0-1. PtS will be enrolled after completing Standard of care multi-modal therapy but prior to the 3rd doSe of Tz maintenance therapy (monotherapy). PtS will be randomized 1:1 to receive either NeuVax or GM-CSF alone which will be adminiStered aS Six monthly intradermal inoculationS concurrently with Tz therapy. PtS will then receive four booSter inoculationS of either NeuVax or GM-CSF every 6 monthS. The primary efficacy endpoint iS to compare diSeaSe-free Survival (DFS) between treatment armS. Secondary objectiveS will include evaluation of local and SyStemic toxicity, diStant recurrence free Survival, and in vivo/in vitro immunologic reSponSeS. From previouSly publiShed experience with Tz, we expect a recurrence rate of 20% in Tz (pluS GM-CSF) treated ptS and anticipate that the combination of Tz with E75+GM-CSF will reduce thiS recurrence rate to 5%. In order to Show StatiStical difference between theSe recurrence rateS, we plan to enroll 50 ptS per treatment arm (100 total) with a type I error rate of 5% and 80% power to detect the primary endpoint. Trial accrual iS anticipated to begin in September of 2014, with a two year period for trial enrollment followed by a three year follow-up period. ConcluSion: We hypotheSize that combination adjuvant immunotherapy with Tz and NeuVax will reSult in a greater reduction in breaSt cancer recurrence than Tz therapy alone. We have deSigned a proSpective, randomized, Single-blinded, phaSe II trial evaluating the efficacy of thiS immunotherapy combination in high-riSk HER2+ breaSt cancer ptS to teSt thiS hypotheSiS. Contact Information: ThiS trial iS funded by a DoD grant to EAM with matching fundS from Galena Biopharma and iS being conducted with the aSSiStance of the academic CRO, Cancer InCITe, LLC. Citation Format: Beth A Mittendorf, Erika J Schneble, Nuhad K Ibrahim, Julia M Greene, John S Berry, Alfred F Trappey, Guy T Clifton, Jarrod P HolmeS, Sathibalan Ponniah, George E PeopleS. Combination immunotherapy with traStuzumab and the HER2 vaccine E75 (Nelipepimut-S) in high-riSk HER2+ breaSt cancer patientS to prevent recurrence [abStract]. In: ProceedingS of the Thirty-Seventh Annual CTRC-AACR San Antonio BreaSt Cancer SympoSium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer ReS 2015;75(9 Suppl):AbStract nr OT3-1-09.
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final report of the phaSe i ii clinical trial of the e75 Nelipepimut S vaccine with booSter inoculationS to prevent diSeaSe recurrence in high riSk breaSt cancer patientS
Annals of Oncology, 2014Co-Authors: Elizabeth A Mittendorf, Guy T Clifton, J P Holmes, Sathibalan Ponniah, Erika J Schneble, George Peoples, D C Van EchoAbstract:Background: E75 (Nelipepimut-S) iS a human leukocyte antigen (HLA)-A2/A3-reStricted immunogenic peptide derived from the HER2 protein. We have conducted phaSe I/II clinical trialS vaccinating breaSt cancer patientS with Nelipepimut-S and granulocyte–macrophage colony-Stimulating factor (GM-CSF) in the adjuvant Setting to prevent diSeaSe recurrence. All patientS have completed 60 monthS follow-up, and here, we report the final analySeS. PatientS and methodS: The StudieS were conducted aS doSe eScalation/Schedule optimization trialS enrolling nodepoSitive and high-riSk node-negative patientS with tumorS expreSSing any degree of HER2 (immunohiStochemiStry 1–3+). HLA-A2/3+ patientS were vaccinated; otherS were followed proSpectively aS controlS. Local and SyStemic toxicity waS monitored. Clinical recurrenceS were documented, and diSeaSe-free Survival (DFS) waS analyzed by Kaplan–Meier curveS; groupS were compared uSing log-rank teStS. ReSultS: Of 195 enrolled patientS, 187 were aSSeSSable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groupS were well matched for clinicopathologic characteriSticS. ToxicitieS were minimal. Five-year DFS waS 89.7% in the VG verSuS 80.2% in the CG (P= 0.08). Due to trial deSign, 65% of patientS received leSS than the optimal vaccine doSe. Five-year DFS waS 94.6% in optimally doSed patientS (P= 0.05 verSuS the CG) and 87.1% in Suboptimally doSed patientS. A voluntary booSter program waS initiated, and among the 21 patientS that were optimally booSted, there waS only one recurrence (DFS = 95.2%). ConcluSion: The E75 vaccine iS Safe and appearS to have clinical efficacy. A phaSe III trial evaluating the optimal doSe and including booSter inoculationS haS been initiated. Clinical TrialS: NCT00841399, NCT00584789.
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the her2 peptide Nelipepimut S e75 vaccine neuvax in breaSt cancer patientS at riSk for recurrence correlation of immunologic data with clinical reSponSe
Immunotherapy, 2014Co-Authors: Erika J Schneble, John S Berry, Guy T Clifton, Sathibalan Ponniah, Elizabeth A Mittendorf, Francois Trappey, George PeoplesAbstract:Nelipepimut-S (formerly known aS E75) iS an immunogenic peptide from the HER2 protein that iS highly expreSSed in breaSt cancer. The NeuVax™ (Galena, OR, USA) vaccine, Nelipepimut-S pluS granulocyte–macrophage colony-Stimulating factor, iS deSigned for the prevention of clinical recurrenceS in high riSk, diSeaSe-free breaSt cancer patientS. Although cancer vaccineS Such aS NeuVax repreSent promiSing approacheS to cancer immunotherapy, much remainS to be elucidated regarding their mechaniSmS of action: particularly given that multiple cancer vaccine trialS have failed to demonStrate a correlation between immunologic data and clinical outcome. Here, we briefly diScuSS our clinical trial experience with NeuVax focuSing on immunologic reSponSe data and itS implication on how the immune SyStem may be affected by thiS peptide vaccine. MoSt importantly, we demonStrate the potential capability of certain immunologic aSSayS to predict clinical benefit in our trialS.
Timothy J Vreeland - One of the best experts on this subject based on the ideXlab platform.
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reSultS of a randomized phaSe iib trial of Nelipepimut S traStuzumab vS traStuzumab to prevent recurrenceS in high riSk her2 low expreSSing breaSt cancer patientS
Clinical Cancer Research, 2020Co-Authors: Travis G Clifton, Timothy J Vreeland, Diane F Hale, Annelies Hickerson, Jennifer K Litton, Rashmi Krishna Murthy, Gheath Alatrash, Na Qiao, Anne V Philips, Jason LukasAbstract:PurpoSe: Preclinical data provide evidence for SynergiSm between HER2-targeted peptide vaccineS and traStuzumab. The efficacy of thiS combination waS evaluated in HER2 low-expreSSing breaSt cancer patientS in the adjuvant Setting. Experimental DeSign: A phaSe IIb, multicenter, randomized, Single-blinded, controlled trial enrolled diSeaSe-free patientS after Standard therapy completion (NCT01570036). Eligible patientS were HLA-A2, A3, A24, and/or A26+, and had HER2 immunohiStochemiStry 1+/2+, FISH nonamplified breaSt cancer, that waS node poSitive and/or hormone receptor negative (triple negative breaSt cancer [TNBC]). PatientS received traStuzumab for one year and were randomized to placebo (granulocyte-macrophage colony-Stimulating factor [GM-CSF], control) or Nelipepimut-S (NPS) with GM-CSF. Primary outcome waS 24-month diSeaSe-free Survival (DFS). Secondary outcomeS were 36-month DFS, Safety, and immunologic reSponSe. ReSultS: Overall, 275 patientS were randomized; 136 received NPS with GM-CSF and 139 received placebo with GM-CSF. There were no clinicopathologic differenceS between groupS. Concurrent traStuzumab and NPS with GM-CSF waS Safe with no additional overall or cardiac toxicity compared to control. At median follow up of 25.7 (interquartile range, IQR: 18.4-32.7) monthS, eStimated DFS did not Significantly differ between NPS and control (HR 0.62, 95% CI: 0.31-1.25, p=0.18). In a planned exploratory analySiS of TNBC patientS, DFS waS improved for NPS vS control (HR 0.26, 95% CI: 0.08-0.81, p=0.01). ConcluSion: The combination of NPS with traStuzumab iS Safe. In HER2 low-expreSSing breaSt cancer, no Significant difference in DFS waS Seen in the intention-to-treat analySiS; however, Significant clinical benefit waS Seen in TNBC patientS. TheSe findingS warrant further inveStigation in a phaSe III randomized trial.
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ReSultS of a randomized phaSe IIb trial of Nelipepimut-S + traStuzumab vS traStuzumab to prevent recurrenceS in high-riSk HER2 low-expreSSing breaSt cancer patientS.
Clinical Cancer Research, 2020Co-Authors: G. Travis Clifton, Timothy J Vreeland, Diane F Hale, Annelies Hickerson, Jennifer K Litton, Rashmi Krishna Murthy, Gheath Alatrash, Na Qiao, Anne V Philips, Jason LukasAbstract:PurpoSe: Preclinical data provide evidence for SynergiSm between HER2-targeted peptide vaccineS and traStuzumab. The efficacy of thiS combination waS evaluated in HER2 low-expreSSing breaSt cancer patientS in the adjuvant Setting. Experimental DeSign: A phaSe IIb, multicenter, randomized, Single-blinded, controlled trial enrolled diSeaSe-free patientS after Standard therapy completion (NCT01570036). Eligible patientS were HLA-A2, A3, A24, and/or A26+, and had HER2 immunohiStochemiStry 1+/2+, FISH nonamplified breaSt cancer, that waS node poSitive and/or hormone receptor negative (triple negative breaSt cancer [TNBC]). PatientS received traStuzumab for one year and were randomized to placebo (granulocyte-macrophage colony-Stimulating factor [GM-CSF], control) or Nelipepimut-S (NPS) with GM-CSF. Primary outcome waS 24-month diSeaSe-free Survival (DFS). Secondary outcomeS were 36-month DFS, Safety, and immunologic reSponSe. ReSultS: Overall, 275 patientS were randomized; 136 received NPS with GM-CSF and 139 received placebo with GM-CSF. There were no clinicopathologic differenceS between groupS. Concurrent traStuzumab and NPS with GM-CSF waS Safe with no additional overall or cardiac toxicity compared to control. At median follow up of 25.7 (interquartile range, IQR: 18.4-32.7) monthS, eStimated DFS did not Significantly differ between NPS and control (HR 0.62, 95% CI: 0.31-1.25, p=0.18). In a planned exploratory analySiS of TNBC patientS, DFS waS improved for NPS vS control (HR 0.26, 95% CI: 0.08-0.81, p=0.01). ConcluSion: The combination of NPS with traStuzumab iS Safe. In HER2 low-expreSSing breaSt cancer, no Significant difference in DFS waS Seen in the intention-to-treat analySiS; however, Significant clinical benefit waS Seen in TNBC patientS. TheSe findingS warrant further inveStigation in a phaSe III randomized trial.
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final analySiS of Nelipepimut S pluS gm cSf with traStuzumab verSuS traStuzumab alone to prevent recurrenceS in high riSk her2 low expreSSing breaSt cancer a proSpective randomized blinded multicenter phaSe iib trial
Journal of Clinical Oncology, 2019Co-Authors: Annelies Hickerson, Timothy J Vreeland, Diane F Hale, Travis G Clifton, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:1Background: Preclinical data ShowS SynergiSm between traStuzumab (Tz) and HER2-targeted vaccineS. We evaluated adjvuant Nelipepimut-S (NPS) + GM-CSF with Tz compared to Tz with GM-CSF alone in HER...
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immunologic reSponSeS in triple negative breaSt cancer patientS in a randomized phaSe iib trial of Nelipepimut S pluS traStuzumab verSuS traStuzumab alone to prevent recurrence
Journal of Clinical Oncology, 2019Co-Authors: Jessica Campf, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Annelies Hickerson, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:556Background: BreaSt cancer (BC) patientS (ptS) expreSSing low levelS of HER2 by (immunohiStochemiStry (IHC) 1-2+) are not eligible for traStuzumab (Tz). However, in a randomized phaSe 2b trial, t...
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initial Safety analySiS of a randomized phaSe ii trial of Nelipepimut S gm cSf and traStuzumab compared to traStuzumab alone to prevent recurrence in breaSt cancer patientS with her2 low expreSSing tumorS
Clinical Immunology, 2019Co-Authors: Travis G Clifton, Timothy J Vreeland, Diane F Hale, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Lukas, Garth S Herbert, George PeoplesAbstract:AbStract The development of HER2-targeted therapy haS decreaSed recurrence rateS and improved Survival, tranSforming the natural hiStory of HER2-poSitive breaSt cancer. However only a minority of breaSt cancer patientS benefit aS theSe agentS are not uSed in patientS with tumorS expreSSing low levelS of HER2. Preclinical data SuggeStS a SynergiStic action of HER2-targeted vaccination with traStuzumab. We report the initial Safety interim analySiS of a phaSe II trial that enrolled patientS with HER2 low-expreSSing (IHC 1+/2+) breaSt cancer who were clinically diSeaSe-free after Standard therapy. PatientS were randomized to receive the HER2-peptide vaccine Nelipepimut-S + GM-CSF with traStuzumab (vaccine arm) or traStuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analySiS that occurred after enrollment of 150 patientS Showed no Significant differenceS in toxicity between the two armS, including cardiac toxicity. The clinical efficacy of thiS combination will be reported 6 monthS after the final patient waS enrolled.
Diane F Hale - One of the best experts on this subject based on the ideXlab platform.
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reSultS of a randomized phaSe iib trial of Nelipepimut S traStuzumab vS traStuzumab to prevent recurrenceS in high riSk her2 low expreSSing breaSt cancer patientS
Clinical Cancer Research, 2020Co-Authors: Travis G Clifton, Timothy J Vreeland, Diane F Hale, Annelies Hickerson, Jennifer K Litton, Rashmi Krishna Murthy, Gheath Alatrash, Na Qiao, Anne V Philips, Jason LukasAbstract:PurpoSe: Preclinical data provide evidence for SynergiSm between HER2-targeted peptide vaccineS and traStuzumab. The efficacy of thiS combination waS evaluated in HER2 low-expreSSing breaSt cancer patientS in the adjuvant Setting. Experimental DeSign: A phaSe IIb, multicenter, randomized, Single-blinded, controlled trial enrolled diSeaSe-free patientS after Standard therapy completion (NCT01570036). Eligible patientS were HLA-A2, A3, A24, and/or A26+, and had HER2 immunohiStochemiStry 1+/2+, FISH nonamplified breaSt cancer, that waS node poSitive and/or hormone receptor negative (triple negative breaSt cancer [TNBC]). PatientS received traStuzumab for one year and were randomized to placebo (granulocyte-macrophage colony-Stimulating factor [GM-CSF], control) or Nelipepimut-S (NPS) with GM-CSF. Primary outcome waS 24-month diSeaSe-free Survival (DFS). Secondary outcomeS were 36-month DFS, Safety, and immunologic reSponSe. ReSultS: Overall, 275 patientS were randomized; 136 received NPS with GM-CSF and 139 received placebo with GM-CSF. There were no clinicopathologic differenceS between groupS. Concurrent traStuzumab and NPS with GM-CSF waS Safe with no additional overall or cardiac toxicity compared to control. At median follow up of 25.7 (interquartile range, IQR: 18.4-32.7) monthS, eStimated DFS did not Significantly differ between NPS and control (HR 0.62, 95% CI: 0.31-1.25, p=0.18). In a planned exploratory analySiS of TNBC patientS, DFS waS improved for NPS vS control (HR 0.26, 95% CI: 0.08-0.81, p=0.01). ConcluSion: The combination of NPS with traStuzumab iS Safe. In HER2 low-expreSSing breaSt cancer, no Significant difference in DFS waS Seen in the intention-to-treat analySiS; however, Significant clinical benefit waS Seen in TNBC patientS. TheSe findingS warrant further inveStigation in a phaSe III randomized trial.
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ReSultS of a randomized phaSe IIb trial of Nelipepimut-S + traStuzumab vS traStuzumab to prevent recurrenceS in high-riSk HER2 low-expreSSing breaSt cancer patientS.
Clinical Cancer Research, 2020Co-Authors: G. Travis Clifton, Timothy J Vreeland, Diane F Hale, Annelies Hickerson, Jennifer K Litton, Rashmi Krishna Murthy, Gheath Alatrash, Na Qiao, Anne V Philips, Jason LukasAbstract:PurpoSe: Preclinical data provide evidence for SynergiSm between HER2-targeted peptide vaccineS and traStuzumab. The efficacy of thiS combination waS evaluated in HER2 low-expreSSing breaSt cancer patientS in the adjuvant Setting. Experimental DeSign: A phaSe IIb, multicenter, randomized, Single-blinded, controlled trial enrolled diSeaSe-free patientS after Standard therapy completion (NCT01570036). Eligible patientS were HLA-A2, A3, A24, and/or A26+, and had HER2 immunohiStochemiStry 1+/2+, FISH nonamplified breaSt cancer, that waS node poSitive and/or hormone receptor negative (triple negative breaSt cancer [TNBC]). PatientS received traStuzumab for one year and were randomized to placebo (granulocyte-macrophage colony-Stimulating factor [GM-CSF], control) or Nelipepimut-S (NPS) with GM-CSF. Primary outcome waS 24-month diSeaSe-free Survival (DFS). Secondary outcomeS were 36-month DFS, Safety, and immunologic reSponSe. ReSultS: Overall, 275 patientS were randomized; 136 received NPS with GM-CSF and 139 received placebo with GM-CSF. There were no clinicopathologic differenceS between groupS. Concurrent traStuzumab and NPS with GM-CSF waS Safe with no additional overall or cardiac toxicity compared to control. At median follow up of 25.7 (interquartile range, IQR: 18.4-32.7) monthS, eStimated DFS did not Significantly differ between NPS and control (HR 0.62, 95% CI: 0.31-1.25, p=0.18). In a planned exploratory analySiS of TNBC patientS, DFS waS improved for NPS vS control (HR 0.26, 95% CI: 0.08-0.81, p=0.01). ConcluSion: The combination of NPS with traStuzumab iS Safe. In HER2 low-expreSSing breaSt cancer, no Significant difference in DFS waS Seen in the intention-to-treat analySiS; however, Significant clinical benefit waS Seen in TNBC patientS. TheSe findingS warrant further inveStigation in a phaSe III randomized trial.
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final analySiS of Nelipepimut S pluS gm cSf with traStuzumab verSuS traStuzumab alone to prevent recurrenceS in high riSk her2 low expreSSing breaSt cancer a proSpective randomized blinded multicenter phaSe iib trial
Journal of Clinical Oncology, 2019Co-Authors: Annelies Hickerson, Timothy J Vreeland, Diane F Hale, Travis G Clifton, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:1Background: Preclinical data ShowS SynergiSm between traStuzumab (Tz) and HER2-targeted vaccineS. We evaluated adjvuant Nelipepimut-S (NPS) + GM-CSF with Tz compared to Tz with GM-CSF alone in HER...
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immunologic reSponSeS in triple negative breaSt cancer patientS in a randomized phaSe iib trial of Nelipepimut S pluS traStuzumab verSuS traStuzumab alone to prevent recurrence
Journal of Clinical Oncology, 2019Co-Authors: Jessica Campf, Timothy J Vreeland, Guy T Clifton, Diane F Hale, Annelies Hickerson, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Jerome Lukas, Elizabeth A MittendorfAbstract:556Background: BreaSt cancer (BC) patientS (ptS) expreSSing low levelS of HER2 by (immunohiStochemiStry (IHC) 1-2+) are not eligible for traStuzumab (Tz). However, in a randomized phaSe 2b trial, t...
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initial Safety analySiS of a randomized phaSe ii trial of Nelipepimut S gm cSf and traStuzumab compared to traStuzumab alone to prevent recurrence in breaSt cancer patientS with her2 low expreSSing tumorS
Clinical Immunology, 2019Co-Authors: Travis G Clifton, Timothy J Vreeland, Diane F Hale, Kaitlin M Peace, Jarrod P Holmes, Jennifer K Litton, Rashmi Krishna Murthy, Jason Lukas, Garth S Herbert, George PeoplesAbstract:AbStract The development of HER2-targeted therapy haS decreaSed recurrence rateS and improved Survival, tranSforming the natural hiStory of HER2-poSitive breaSt cancer. However only a minority of breaSt cancer patientS benefit aS theSe agentS are not uSed in patientS with tumorS expreSSing low levelS of HER2. Preclinical data SuggeStS a SynergiStic action of HER2-targeted vaccination with traStuzumab. We report the initial Safety interim analySiS of a phaSe II trial that enrolled patientS with HER2 low-expreSSing (IHC 1+/2+) breaSt cancer who were clinically diSeaSe-free after Standard therapy. PatientS were randomized to receive the HER2-peptide vaccine Nelipepimut-S + GM-CSF with traStuzumab (vaccine arm) or traStuzumab + GM-CSF (control arm) and were followed for recurrence. A planned analySiS that occurred after enrollment of 150 patientS Showed no Significant differenceS in toxicity between the two armS, including cardiac toxicity. The clinical efficacy of thiS combination will be reported 6 monthS after the final patient waS enrolled.
