420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study

Adi Diab; Scott Tykodi; Gregory Daniels; Michele Maio; Brendan Curti; Karl Lewis; Sekwon Jang; Ewa Kalinka; Igor Puzanov; Alexander Spira; Daniel Cho; Shanhong Guan; Erika Puente; Ute Hoch; Sue Currie; Tuan Nguyen; Wei Lin; Mary Tagliaferri; Jonathan Zalevsky; Mario Sznol; Michael Hurwitz

420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study

Adi Diab, Scott Tykodi, Gregory Daniels, Michele Maio, Brendan Curti, Karl Lewis, Sekwon Jang, Ewa Kalinka, Igor Puzanov, Alexander Spira, Daniel Cho, Shanhong Guan, Erika Puente, Ute Hoch, Sue Currie, Tuan Nguyen, Wei Lin, Mary Tagliaferri, Jonathan Zalevsky, Mario SznolMichael Hurwitz

Earle A. Chiles Research Institute (EACRI)

Research output: Other contribution

Abstract

Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial (NCT02983045),1 leading to FDA Breakthrough Therapy Designation. We present updated clinical results from PIVOT-02 in first-line metMEL, and biomarkers of response.

Methods 41 patients with previously untreated stage IV melanoma (known PD-L1 status by immunohistochemistry; 28–8 PharmDx) received ≥1 dose of BEMPEG(0.006 mg/kg) plus NIVO(360 mg) q3wks; 38 patients were efficacy-evaluable (≥1 post-baseline tumor scan). Primary endpoints were safety and objective response rate (ORR; RECIST v1.1; BICR); other endpoints included PFS, OS and biomarkers. Polyfunctional strength index (PSI) of circulating lymphocytes (determined using single-cell cytokine analysis [Isoplexis]) and eosinophil count (determined from hematology analysis) at baseline and Cycle1-Day8 were analyzed using the median cut-off for correlations with ORR and PFS. Biomarkers, including CD8+tumor infiltrating lymphocytes (TIL) and interferon-gamma (IFNg) gene expression profile (GEP), were measured in baseline tumor biopsies and analyzed for correlation with ORR and PFS.

Results At median follow-up of 25.7 months (15May2020), ORR by BICR was 53% (20/38 patients). Complete response occurred in 13/38 patients (34%): 23% PD-L1-negative (Conclusions BEMPEG plus NIVO was well tolerated in first-line metMEL, with durable and further deepening of responses, regardless of baseline PD-L1 status. At 25.7 months‘ follow-up, mPFS and mOS were not reached. Early on-treatment (Day8) increases in CD8+PSI and eosinophils in blood were identified as non-invasive biomarkers of response that are detectable well before clinical measures of response. A phase 3 trial evaluating BEMPEG plus NIVO in first-line metMEL is enrolling(NCT03635983).

Trial Registration NCT02983045

Ethics Approval The study was approved by the institutional review board of each participating site.

Reference

Diab A, Puzanov I, Maio M, et al. Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study. Oral presentation at SITC; November 6–10, 2019; National Harbor, MD, USA. Abstract #O35.

http://dx.doi.org/10.1136/jitc-2020-SITC2020.0420

Original language	Undefined/Unknown
State	Published - Nov 9 2020

Publication series

Name	Articles, Abstracts, and Reports

Access to Document

http://digitalcommons.psjhealth.org/publications/3966

Cite this

Diab, A., Tykodi, S., Daniels, G., Maio, M., Curti, B., Lewis, K., Jang, S., Kalinka, E., Puzanov, I., Spira, A., Cho, D., Guan, S., Puente, E., Hoch, U., Currie, S., Nguyen, T., Lin, W., Tagliaferri, M., Zalevsky, J., ... Hurwitz, M. (2020, Nov 9). 420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study. http://digitalcommons.psjhealth.org/publications/3966

@misc{0542dc682de548fb8fc059fc532a8e5e,

title = "420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study",

abstract = "Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial (NCT02983045),1 leading to FDA Breakthrough Therapy Designation. We present updated clinical results from PIVOT-02 in first-line metMEL, and biomarkers of response. Methods 41 patients with previously untreated stage IV melanoma (known PD-L1 status by immunohistochemistry; 28–8 PharmDx) received ≥1 dose of BEMPEG(0.006 mg/kg) plus NIVO(360 mg) q3wks; 38 patients were efficacy-evaluable (≥1 post-baseline tumor scan). Primary endpoints were safety and objective response rate (ORR; RECIST v1.1; BICR); other endpoints included PFS, OS and biomarkers. Polyfunctional strength index (PSI) of circulating lymphocytes (determined using single-cell cytokine analysis [Isoplexis]) and eosinophil count (determined from hematology analysis) at baseline and Cycle1-Day8 were analyzed using the median cut-off for correlations with ORR and PFS. Biomarkers, including CD8+tumor infiltrating lymphocytes (TIL) and interferon-gamma (IFNg) gene expression profile (GEP), were measured in baseline tumor biopsies and analyzed for correlation with ORR and PFS. Results At median follow-up of 25.7 months (15May2020), ORR by BICR was 53% (20/38 patients). Complete response occurred in 13/38 patients (34%): 23% PD-L1-negative (Conclusions BEMPEG plus NIVO was well tolerated in first-line metMEL, with durable and further deepening of responses, regardless of baseline PD-L1 status. At 25.7 months{\textquoteleft} follow-up, mPFS and mOS were not reached. Early on-treatment (Day8) increases in CD8+PSI and eosinophils in blood were identified as non-invasive biomarkers of response that are detectable well before clinical measures of response. A phase 3 trial evaluating BEMPEG plus NIVO in first-line metMEL is enrolling(NCT03635983). Trial Registration NCT02983045 Ethics Approval The study was approved by the institutional review board of each participating site. Reference Diab A, Puzanov I, Maio M, et al. Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study. Oral presentation at SITC; November 6–10, 2019; National Harbor, MD, USA. Abstract #O35. http://dx.doi.org/10.1136/jitc-2020-SITC2020.0420",

author = "Adi Diab and Scott Tykodi and Gregory Daniels and Michele Maio and Brendan Curti and Karl Lewis and Sekwon Jang and Ewa Kalinka and Igor Puzanov and Alexander Spira and Daniel Cho and Shanhong Guan and Erika Puente and Ute Hoch and Sue Currie and Tuan Nguyen and Wei Lin and Mary Tagliaferri and Jonathan Zalevsky and Mario Sznol and Michael Hurwitz",

year = "2020",

month = nov,

day = "9",

language = "Undefined/Unknown",

series = "Articles, Abstracts, and Reports",

type = "Other",

}

Diab, A, Tykodi, S, Daniels, G, Maio, M, Curti, B, Lewis, K, Jang, S, Kalinka, E, Puzanov, I, Spira, A, Cho, D, Guan, S, Puente, E, Hoch, U, Currie, S, Nguyen, T, Lin, W, Tagliaferri, M, Zalevsky, J, Sznol, M & Hurwitz, M 2020, 420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study.. <http://digitalcommons.psjhealth.org/publications/3966>

TY - GEN

T1 - 420 Progression-free survival and biomarker correlates of response with BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: results from the PIVOT-02 study

AU - Diab, Adi

AU - Tykodi, Scott

AU - Daniels, Gregory

AU - Maio, Michele

AU - Curti, Brendan

AU - Lewis, Karl

AU - Jang, Sekwon

AU - Kalinka, Ewa

AU - Puzanov, Igor

AU - Spira, Alexander

AU - Cho, Daniel

AU - Guan, Shanhong

AU - Puente, Erika

AU - Hoch, Ute

AU - Currie, Sue

AU - Nguyen, Tuan

AU - Lin, Wei

AU - Tagliaferri, Mary

AU - Zalevsky, Jonathan

AU - Sznol, Mario

AU - Hurwitz, Michael

PY - 2020/11/9

Y1 - 2020/11/9

N2 - Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial (NCT02983045),1 leading to FDA Breakthrough Therapy Designation. We present updated clinical results from PIVOT-02 in first-line metMEL, and biomarkers of response. Methods 41 patients with previously untreated stage IV melanoma (known PD-L1 status by immunohistochemistry; 28–8 PharmDx) received ≥1 dose of BEMPEG(0.006 mg/kg) plus NIVO(360 mg) q3wks; 38 patients were efficacy-evaluable (≥1 post-baseline tumor scan). Primary endpoints were safety and objective response rate (ORR; RECIST v1.1; BICR); other endpoints included PFS, OS and biomarkers. Polyfunctional strength index (PSI) of circulating lymphocytes (determined using single-cell cytokine analysis [Isoplexis]) and eosinophil count (determined from hematology analysis) at baseline and Cycle1-Day8 were analyzed using the median cut-off for correlations with ORR and PFS. Biomarkers, including CD8+tumor infiltrating lymphocytes (TIL) and interferon-gamma (IFNg) gene expression profile (GEP), were measured in baseline tumor biopsies and analyzed for correlation with ORR and PFS. Results At median follow-up of 25.7 months (15May2020), ORR by BICR was 53% (20/38 patients). Complete response occurred in 13/38 patients (34%): 23% PD-L1-negative (Conclusions BEMPEG plus NIVO was well tolerated in first-line metMEL, with durable and further deepening of responses, regardless of baseline PD-L1 status. At 25.7 months‘ follow-up, mPFS and mOS were not reached. Early on-treatment (Day8) increases in CD8+PSI and eosinophils in blood were identified as non-invasive biomarkers of response that are detectable well before clinical measures of response. A phase 3 trial evaluating BEMPEG plus NIVO in first-line metMEL is enrolling(NCT03635983). Trial Registration NCT02983045 Ethics Approval The study was approved by the institutional review board of each participating site. Reference Diab A, Puzanov I, Maio M, et al. Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study. Oral presentation at SITC; November 6–10, 2019; National Harbor, MD, USA. Abstract #O35. http://dx.doi.org/10.1136/jitc-2020-SITC2020.0420

AB - Background An unmet need exists for novel therapies that produce deep and durable responses in more patients with metastatic melanoma (metMEL). Encouraging clinical activity was observed with the CD122-preferential IL-2 pathway agonist bempegaldesleukin(BEMPEG) plus nivolumab(NIVO) in first-line metMEL in the phase 1/2 PIVOT-02 trial (NCT02983045),1 leading to FDA Breakthrough Therapy Designation. We present updated clinical results from PIVOT-02 in first-line metMEL, and biomarkers of response. Methods 41 patients with previously untreated stage IV melanoma (known PD-L1 status by immunohistochemistry; 28–8 PharmDx) received ≥1 dose of BEMPEG(0.006 mg/kg) plus NIVO(360 mg) q3wks; 38 patients were efficacy-evaluable (≥1 post-baseline tumor scan). Primary endpoints were safety and objective response rate (ORR; RECIST v1.1; BICR); other endpoints included PFS, OS and biomarkers. Polyfunctional strength index (PSI) of circulating lymphocytes (determined using single-cell cytokine analysis [Isoplexis]) and eosinophil count (determined from hematology analysis) at baseline and Cycle1-Day8 were analyzed using the median cut-off for correlations with ORR and PFS. Biomarkers, including CD8+tumor infiltrating lymphocytes (TIL) and interferon-gamma (IFNg) gene expression profile (GEP), were measured in baseline tumor biopsies and analyzed for correlation with ORR and PFS. Results At median follow-up of 25.7 months (15May2020), ORR by BICR was 53% (20/38 patients). Complete response occurred in 13/38 patients (34%): 23% PD-L1-negative (Conclusions BEMPEG plus NIVO was well tolerated in first-line metMEL, with durable and further deepening of responses, regardless of baseline PD-L1 status. At 25.7 months‘ follow-up, mPFS and mOS were not reached. Early on-treatment (Day8) increases in CD8+PSI and eosinophils in blood were identified as non-invasive biomarkers of response that are detectable well before clinical measures of response. A phase 3 trial evaluating BEMPEG plus NIVO in first-line metMEL is enrolling(NCT03635983). Trial Registration NCT02983045 Ethics Approval The study was approved by the institutional review board of each participating site. Reference Diab A, Puzanov I, Maio M, et al. Clinical activity of BEMPEG plus NIVO in previously untreated patients with metastatic melanoma: updated results from the phase 1/2 PIVOT-02 study. Oral presentation at SITC; November 6–10, 2019; National Harbor, MD, USA. Abstract #O35. http://dx.doi.org/10.1136/jitc-2020-SITC2020.0420

M3 - Other contribution

T3 - Articles, Abstracts, and Reports

ER -