Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors

Juanita S. Lopez; Ross Camidge; Marco Iafolla; Sylvie Rottey; Martin Schuler; Matthew Hellmann; Ani Balmanoukian; Luc Dirix; Michael Gordon; Ryan Sullivan; Bryan S. Henick; Chares Drake; Kit Wong; Patricia LoRusso; Patrick Ott; Lawrence Fong; Aglaia Schiza; Jeffrey Yachnin; Christian Ottensmeier; Fadi Braiteh; Joanna Bendell; Rom Leidner; George Fisher; Guy Jerusalem; Laura Molenaar-Kuijsten; Marcus Schmidt; Scott A. Laurie; Raid Aljumaily; Achim Rittmeyer; Eelke Gort; Ignacio Melero; Lars Mueller; Rachel Sabado; Patrick Twomey; Jack Huang; Manesh Yadav; Jingbin Zhang; Felicitas Mueller; Evelyna Derhovanessian; Ugur Sahin; Ozlem Tureci; Thomas Powels

Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors

Juanita S. Lopez, Ross Camidge, Marco Iafolla, Sylvie Rottey, Martin Schuler, Matthew Hellmann, Ani Balmanoukian, Luc Dirix, Michael Gordon, Ryan Sullivan, Bryan S. Henick, Chares Drake, Kit Wong, Patricia LoRusso, Patrick Ott, Lawrence Fong, Aglaia Schiza, Jeffrey Yachnin, Christian Ottensmeier, Fadi BraitehJoanna Bendell, Rom Leidner, George Fisher, Guy Jerusalem, Laura Molenaar-Kuijsten, Marcus Schmidt, Scott A. Laurie, Raid Aljumaily, Achim Rittmeyer, Eelke Gort, Ignacio Melero, Lars Mueller, Rachel Sabado, Patrick Twomey, Jack Huang, Manesh Yadav, Jingbin Zhang, Felicitas Mueller, Evelyna Derhovanessian, Ugur Sahin, Ozlem Tureci, Thomas Powels

Earle A. Chiles Research Institute (EACRI)

Research output: Other contribution

Abstract

Background: Neoantigens arising from somatic mutations are attractive targets for cancer immunotherapy as they may be recognized as foreign by the immune system. RO7198457, a systemically administered RNA-Lipoplex iNeST was designed to stimulate T cell responses against neoantigens. A first-in-human Phase Ib study of RO7198457, in combination with the aPD-L1 antibody atezolizumab is being conducted in patients with locally advanced or metastatic solid tumors. Methods: RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered i.v. in weekly and bi-weekly intervals during the 12-week induction stage and every 24 weeks during the maintenance stage. Atezolizumab 1200 mg was administered on Day 1 of each 21-day cycle. Results: In total, 132 patients enrolled in cohorts with doses ranging from 15-50 μg RO7198457 in combination with atezolizumab. Most common tumor types were NSCLC, TNBC, melanoma and CRC. The median number of prior therapies was 3 (range 1-11). 39% of patients received prior immunotherapy. Most patients had low levels of PD-L1 expression (93% patients with ex vivo ELISPOT or MHC multimer analysis. Induction of up to 6% MHC multimer-stained CD8+ T-cells with memory phenotype was observed in peripheral blood. RO7198457-induced T cells against multiple neoantigens that were detected in post-treatment tumor biopsies. Of 108 patients who underwent at least one tumor assessment, 9 responded (ORR 8%, including 1 CR) and 53 had SD (49%). Conclusion: RO7198457 in combination with atezolizumab has a manageable safety profile consistent with the mechanisms of action of the study drugs and induces significant levels of neoantigen-specific immune responses. A randomized Ph2 study of RO7198457 1L melanoma patients in combination with pembrolizumab has been initiated, and two randomized clinical trials are planned for the adjuvant treatment of patients with NSCLC and CRC.

Original language	Undefined/Unknown
State	Published - Nov 23 2020

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Name	Articles, Abstracts, and Reports

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Lopez, J. S., Camidge, R., Iafolla, M., Rottey, S., Schuler, M., Hellmann, M., Balmanoukian, A., Dirix, L., Gordon, M., Sullivan, R., Henick, B. S., Drake, C., Wong, K., LoRusso, P., Ott, P., Fong, L., Schiza, A., Yachnin, J., Ottensmeier, C., ... Powels, T. (2020, Nov 23). Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors. http://digitalcommons.psjhealth.org/publications/3932

@misc{7814b1005e6f416cae89f5ccfaa23141,

title = "Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors",

abstract = "Background: Neoantigens arising from somatic mutations are attractive targets for cancer immunotherapy as they may be recognized as foreign by the immune system. RO7198457, a systemically administered RNA-Lipoplex iNeST was designed to stimulate T cell responses against neoantigens. A first-in-human Phase Ib study of RO7198457, in combination with the aPD-L1 antibody atezolizumab is being conducted in patients with locally advanced or metastatic solid tumors. Methods: RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered i.v. in weekly and bi-weekly intervals during the 12-week induction stage and every 24 weeks during the maintenance stage. Atezolizumab 1200 mg was administered on Day 1 of each 21-day cycle. Results: In total, 132 patients enrolled in cohorts with doses ranging from 15-50 μg RO7198457 in combination with atezolizumab. Most common tumor types were NSCLC, TNBC, melanoma and CRC. The median number of prior therapies was 3 (range 1-11). 39% of patients received prior immunotherapy. Most patients had low levels of PD-L1 expression (93% patients with ex vivo ELISPOT or MHC multimer analysis. Induction of up to 6% MHC multimer-stained CD8+ T-cells with memory phenotype was observed in peripheral blood. RO7198457-induced T cells against multiple neoantigens that were detected in post-treatment tumor biopsies. Of 108 patients who underwent at least one tumor assessment, 9 responded (ORR 8%, including 1 CR) and 53 had SD (49%). Conclusion: RO7198457 in combination with atezolizumab has a manageable safety profile consistent with the mechanisms of action of the study drugs and induces significant levels of neoantigen-specific immune responses. A randomized Ph2 study of RO7198457 1L melanoma patients in combination with pembrolizumab has been initiated, and two randomized clinical trials are planned for the adjuvant treatment of patients with NSCLC and CRC.",

author = "Lopez, {Juanita S.} and Ross Camidge and Marco Iafolla and Sylvie Rottey and Martin Schuler and Matthew Hellmann and Ani Balmanoukian and Luc Dirix and Michael Gordon and Ryan Sullivan and Henick, {Bryan S.} and Chares Drake and Kit Wong and Patricia LoRusso and Patrick Ott and Lawrence Fong and Aglaia Schiza and Jeffrey Yachnin and Christian Ottensmeier and Fadi Braiteh and Joanna Bendell and Rom Leidner and George Fisher and Guy Jerusalem and Laura Molenaar-Kuijsten and Marcus Schmidt and Laurie, {Scott A.} and Raid Aljumaily and Achim Rittmeyer and Eelke Gort and Ignacio Melero and Lars Mueller and Rachel Sabado and Patrick Twomey and Jack Huang and Manesh Yadav and Jingbin Zhang and Felicitas Mueller and Evelyna Derhovanessian and Ugur Sahin and Ozlem Tureci and Thomas Powels",

year = "2020",

month = nov,

day = "23",

language = "Undefined/Unknown",

series = "Articles, Abstracts, and Reports",

type = "Other",

}

Lopez, JS, Camidge, R, Iafolla, M, Rottey, S, Schuler, M, Hellmann, M, Balmanoukian, A, Dirix, L, Gordon, M, Sullivan, R, Henick, BS, Drake, C, Wong, K, LoRusso, P, Ott, P, Fong, L, Schiza, A, Yachnin, J, Ottensmeier, C, Braiteh, F, Bendell, J, Leidner, R, Fisher, G, Jerusalem, G, Molenaar-Kuijsten, L, Schmidt, M, Laurie, SA, Aljumaily, R, Rittmeyer, A, Gort, E, Melero, I, Mueller, L, Sabado, R, Twomey, P, Huang, J, Yadav, M, Zhang, J, Mueller, F, Derhovanessian, E, Sahin, U, Tureci, O & Powels, T 2020, Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors.. <http://digitalcommons.psjhealth.org/publications/3932>

TY - GEN

T1 - Abstract CT301: A phase Ib study to evaluate RO7198457, an individualized Neoantigen Specific immunoTherapy (iNeST), in combination with atezolizumab in patients with locally advanced or metastatic solid tumors

AU - Lopez, Juanita S.

AU - Camidge, Ross

AU - Iafolla, Marco

AU - Rottey, Sylvie

AU - Schuler, Martin

AU - Hellmann, Matthew

AU - Balmanoukian, Ani

AU - Dirix, Luc

AU - Gordon, Michael

AU - Sullivan, Ryan

AU - Henick, Bryan S.

AU - Drake, Chares

AU - Wong, Kit

AU - LoRusso, Patricia

AU - Ott, Patrick

AU - Fong, Lawrence

AU - Schiza, Aglaia

AU - Yachnin, Jeffrey

AU - Ottensmeier, Christian

AU - Braiteh, Fadi

AU - Bendell, Joanna

AU - Leidner, Rom

AU - Fisher, George

AU - Jerusalem, Guy

AU - Molenaar-Kuijsten, Laura

AU - Schmidt, Marcus

AU - Laurie, Scott A.

AU - Aljumaily, Raid

AU - Rittmeyer, Achim

AU - Gort, Eelke

AU - Melero, Ignacio

AU - Mueller, Lars

AU - Sabado, Rachel

AU - Twomey, Patrick

AU - Huang, Jack

AU - Yadav, Manesh

AU - Zhang, Jingbin

AU - Mueller, Felicitas

AU - Derhovanessian, Evelyna

AU - Sahin, Ugur

AU - Tureci, Ozlem

AU - Powels, Thomas

PY - 2020/11/23

Y1 - 2020/11/23

N2 - Background: Neoantigens arising from somatic mutations are attractive targets for cancer immunotherapy as they may be recognized as foreign by the immune system. RO7198457, a systemically administered RNA-Lipoplex iNeST was designed to stimulate T cell responses against neoantigens. A first-in-human Phase Ib study of RO7198457, in combination with the aPD-L1 antibody atezolizumab is being conducted in patients with locally advanced or metastatic solid tumors. Methods: RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered i.v. in weekly and bi-weekly intervals during the 12-week induction stage and every 24 weeks during the maintenance stage. Atezolizumab 1200 mg was administered on Day 1 of each 21-day cycle. Results: In total, 132 patients enrolled in cohorts with doses ranging from 15-50 μg RO7198457 in combination with atezolizumab. Most common tumor types were NSCLC, TNBC, melanoma and CRC. The median number of prior therapies was 3 (range 1-11). 39% of patients received prior immunotherapy. Most patients had low levels of PD-L1 expression (93% patients with ex vivo ELISPOT or MHC multimer analysis. Induction of up to 6% MHC multimer-stained CD8+ T-cells with memory phenotype was observed in peripheral blood. RO7198457-induced T cells against multiple neoantigens that were detected in post-treatment tumor biopsies. Of 108 patients who underwent at least one tumor assessment, 9 responded (ORR 8%, including 1 CR) and 53 had SD (49%). Conclusion: RO7198457 in combination with atezolizumab has a manageable safety profile consistent with the mechanisms of action of the study drugs and induces significant levels of neoantigen-specific immune responses. A randomized Ph2 study of RO7198457 1L melanoma patients in combination with pembrolizumab has been initiated, and two randomized clinical trials are planned for the adjuvant treatment of patients with NSCLC and CRC.

AB - Background: Neoantigens arising from somatic mutations are attractive targets for cancer immunotherapy as they may be recognized as foreign by the immune system. RO7198457, a systemically administered RNA-Lipoplex iNeST was designed to stimulate T cell responses against neoantigens. A first-in-human Phase Ib study of RO7198457, in combination with the aPD-L1 antibody atezolizumab is being conducted in patients with locally advanced or metastatic solid tumors. Methods: RO7198457 is manufactured on a per-patient basis and contains up to 20 tumor-specific neoepitopes. Nine doses of RO7198457 were administered i.v. in weekly and bi-weekly intervals during the 12-week induction stage and every 24 weeks during the maintenance stage. Atezolizumab 1200 mg was administered on Day 1 of each 21-day cycle. Results: In total, 132 patients enrolled in cohorts with doses ranging from 15-50 μg RO7198457 in combination with atezolizumab. Most common tumor types were NSCLC, TNBC, melanoma and CRC. The median number of prior therapies was 3 (range 1-11). 39% of patients received prior immunotherapy. Most patients had low levels of PD-L1 expression (93% patients with ex vivo ELISPOT or MHC multimer analysis. Induction of up to 6% MHC multimer-stained CD8+ T-cells with memory phenotype was observed in peripheral blood. RO7198457-induced T cells against multiple neoantigens that were detected in post-treatment tumor biopsies. Of 108 patients who underwent at least one tumor assessment, 9 responded (ORR 8%, including 1 CR) and 53 had SD (49%). Conclusion: RO7198457 in combination with atezolizumab has a manageable safety profile consistent with the mechanisms of action of the study drugs and induces significant levels of neoantigen-specific immune responses. A randomized Ph2 study of RO7198457 1L melanoma patients in combination with pembrolizumab has been initiated, and two randomized clinical trials are planned for the adjuvant treatment of patients with NSCLC and CRC.

M3 - Other contribution

T3 - Articles, Abstracts, and Reports

ER -