Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit

Benjamin J. Bulen; Nickolay A. Khazanov; Daniel H. Hovelson; Laura E. Lamb; Marc Matrana; Mark E. Burkard; Eddy Shih Hsin Yang; William J. Edenfield; Elizabeth Claire Dees; Adedayo A. Onitilo; Gary L. Buchschacher; Alan M. Miller; Benjamin M. Parsons; Timothy R. Wassenaar; Jennifer M. Suga; Robert D. Siegel; William Irvin; Suresh Nair; Jennifer N. Slim; Jamal Misleh; Jamil Khatri; Gregory A. Masters; Sachdev Thomas; Malek M. Safa; Daniel M. Anderson; Jonathan Mowers; Anna C. Dusenbery; Stephanie Drewery; Komal Plouffe; Travis Reeder; Hana Vakil; Lynnae Patrias; Amanda Falzetta; Ryan Hamilton; Kat Kwiatkowski; D. Bryan Johnson; Daniel R. Rhodes; Scott A. Tomlins

doi:10.1158/2767-9764.CRC-23-0036

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit

Benjamin J. Bulen, Nickolay A. Khazanov, Daniel H. Hovelson, Laura E. Lamb, Marc Matrana, Mark E. Burkard, Eddy Shih Hsin Yang, William J. Edenfield, Elizabeth Claire Dees, Adedayo A. Onitilo, Gary L. Buchschacher, Alan M. Miller, Benjamin M. Parsons, Timothy R. Wassenaar, Jennifer M. Suga, Robert D. Siegel, William Irvin, Suresh Nair, Jennifer N. Slim, Jamal MislehJamil Khatri, Gregory A. Masters, Sachdev Thomas, Malek M. Safa, Daniel M. Anderson, Jonathan Mowers, Anna C. Dusenbery, Stephanie Drewery, Komal Plouffe, Travis Reeder, Hana Vakil, Lynnae Patrias, Amanda Falzetta, Ryan Hamilton, Kat Kwiatkowski, D. Bryan Johnson, Daniel R. Rhodes, Scott A. Tomlins

Research output: Contribution to journal › Article › peer-review

Abstract

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PDL1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.

Original language	English
Pages (from-to)	1335-1349
Number of pages	15
Journal	Cancer Research Communications
Volume	3
Issue number	7
DOIs	https://doi.org/10.1158/2767-9764.CRC-23-0036
State	Published - Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors.

Funding

The authors thank Arvinda Padmanabhan (Baptist Health, Louisville, KY), Vallathucherry Harish (Hayworth Cancer Center at High Point Medical Center, High Point, NC), William Schulz (UW-Swedish American, Rockford, IL), Benjamin Durkee (Swedish American, Rockford, IL), and Han Koh (Kaiser Permanente Southern California, Bellflower, CA) as principal investigators and for their sites\u2019 contribution to the study. The study was supported by Strata Oncology. B.J. Bulen is an employee of Strata Oncology and this is author-owned work. D.H. Hovelson reports personal fees and other from Strata Oncology outside the submitted work. L.E. Lamb reports personal fees from Strata Oncology during the conduct of the study. M.E. Burkard reports grants and personal fees from Strata Oncology during the conduct of the study; grants and personal fees from Strata Oncology outside the submitted work. E.S.-H. Yang reports other from Strata Oncology during the conduct of the study; grants from Eli Lilly; other from Clovis, Bayer, and AstraZeneca outside the submitted work. W.J. Edenfield reports other from Chimerix outside the submitted work. J.M. Suga reports grants and non-financial support from Strata Oncology during the conduct of the study. S. Nair reports grants from BMS, Mirati Therapeutics, Merck, and Strata Oncology outside the submitted work. J. Mowers is an equity holder and/or employee of Strata Oncology. A.C. Dusenbery is an equity holder and/or employee of Strata Oncology. S. Drewery reports personal fees from Strata Oncology during the conduct of the study. K. Plouffe reports personal fees from Strata Oncology outside the submitted work. H. Vakil reports employment by Strata Oncology. K. Kwiatkowski reports personal fees from Strata Oncology outside the submitted work. D.B. Johnson reports other from Strata Oncology during the conduct of the study; in addition, D.B. Johnson has a patent to 63/277,158 pending. D.R. Rhodes reports personal fees and other from Strata Oncology and other from Javelin Oncology outside the submitted work; and B.J. Bulen, N.A. Khazanov, D.H. Hovelson, L.E. Lamb, J. Mowers, A.C. Dusenbery, S. Drewery, K. Plouffe, T. Reeder, H. Vakil, L. Pa-trias, A. Falzetta, R. Hamilton, K. Kwiatkowski, D.B. Johnson, D.R. Rhodes, and S.A. Tomlins are/were equity holders and/or employees of Strata Oncology. D.R. Rhodes, N.A. Khazanov, D.B. Johnson, and S.A. Tomlins are named as co-inventors on a pending patent to Strata Oncology related to the IRS model described herein. S.A. Tomlins reports other from Strata Oncology during the conduct of the study; other from Javelin Oncology and grants and personal fees from Astellas outside the submitted work; in addition, S.A. Tomlins has a patent to co-author on a pending patent to Strata Oncology related to the IRS model described herein pending. No disclosures were reported by the other authors.

Funders	Funder number
Han Koh
Strata Oncology
Mirati Therapeutics
Merck

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/2767-9764.CRC-23-0036

Cite this

Bulen, B. J., Khazanov, N. A., Hovelson, D. H., Lamb, L. E., Matrana, M., Burkard, M. E., Yang, E. S. H., Edenfield, W. J., Dees, E. C., Onitilo, A. A., Buchschacher, G. L., Miller, A. M., Parsons, B. M., Wassenaar, T. R., Suga, J. M., Siegel, R. D., Irvin, W., Nair, S., Slim, J. N., ... Tomlins, S. A. (2023). Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit. Cancer Research Communications, 3(7), 1335-1349. https://doi.org/10.1158/2767-9764.CRC-23-0036

@article{5ecf6943d65b4d13b04e7b8c706a565b,

title = "Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit",

abstract = "Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PDL1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.",

author = "Bulen, {Benjamin J.} and Khazanov, {Nickolay A.} and Hovelson, {Daniel H.} and Lamb, {Laura E.} and Marc Matrana and Burkard, {Mark E.} and Yang, {Eddy Shih Hsin} and Edenfield, {William J.} and Dees, {Elizabeth Claire} and Onitilo, {Adedayo A.} and Buchschacher, {Gary L.} and Miller, {Alan M.} and Parsons, {Benjamin M.} and Wassenaar, {Timothy R.} and Suga, {Jennifer M.} and Siegel, {Robert D.} and William Irvin and Suresh Nair and Slim, {Jennifer N.} and Jamal Misleh and Jamil Khatri and Masters, {Gregory A.} and Sachdev Thomas and Safa, {Malek M.} and Anderson, {Daniel M.} and Jonathan Mowers and Dusenbery, {Anna C.} and Stephanie Drewery and Komal Plouffe and Travis Reeder and Hana Vakil and Lynnae Patrias and Amanda Falzetta and Ryan Hamilton and Kat Kwiatkowski and Johnson, {D. Bryan} and Rhodes, {Daniel R.} and Tomlins, {Scott A.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2023",

month = jul,

doi = "10.1158/2767-9764.CRC-23-0036",

language = "English",

volume = "3",

pages = "1335--1349",

number = "7",

}

Bulen, BJ, Khazanov, NA, Hovelson, DH, Lamb, LE, Matrana, M, Burkard, ME, Yang, ESH, Edenfield, WJ, Dees, EC, Onitilo, AA, Buchschacher, GL, Miller, AM, Parsons, BM, Wassenaar, TR, Suga, JM, Siegel, RD, Irvin, W, Nair, S, Slim, JN, Misleh, J, Khatri, J, Masters, GA, Thomas, S, Safa, MM, Anderson, DM, Mowers, J, Dusenbery, AC, Drewery, S, Plouffe, K, Reeder, T, Vakil, H, Patrias, L, Falzetta, A, Hamilton, R, Kwiatkowski, K, Johnson, DB, Rhodes, DR & Tomlins, SA 2023, 'Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit', Cancer Research Communications, vol. 3, no. 7, pp. 1335-1349. https://doi.org/10.1158/2767-9764.CRC-23-0036

TY - JOUR

T1 - Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit

AU - Bulen, Benjamin J.

AU - Khazanov, Nickolay A.

AU - Hovelson, Daniel H.

AU - Lamb, Laura E.

AU - Matrana, Marc

AU - Burkard, Mark E.

AU - Yang, Eddy Shih Hsin

AU - Edenfield, William J.

AU - Dees, Elizabeth Claire

AU - Onitilo, Adedayo A.

AU - Buchschacher, Gary L.

AU - Miller, Alan M.

AU - Parsons, Benjamin M.

AU - Wassenaar, Timothy R.

AU - Suga, Jennifer M.

AU - Siegel, Robert D.

AU - Irvin, William

AU - Nair, Suresh

AU - Slim, Jennifer N.

AU - Misleh, Jamal

AU - Khatri, Jamil

AU - Masters, Gregory A.

AU - Thomas, Sachdev

AU - Safa, Malek M.

AU - Anderson, Daniel M.

AU - Mowers, Jonathan

AU - Dusenbery, Anna C.

AU - Drewery, Stephanie

AU - Plouffe, Komal

AU - Reeder, Travis

AU - Vakil, Hana

AU - Patrias, Lynnae

AU - Falzetta, Amanda

AU - Hamilton, Ryan

AU - Kwiatkowski, Kat

AU - Johnson, D. Bryan

AU - Rhodes, Daniel R.

AU - Tomlins, Scott A.

PY - 2023/7

Y1 - 2023/7

N2 - Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PDL1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.

AB - Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PDL1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment.

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Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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