Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

R. Perets; J. Bar; D. W. Rasco; M. J. Ahn; K. Yoh; D. W. Kim; A. Nagrial; M. Satouchi; D. H. Lee; D. R. Spigel; D. Kotasek; M. Gutierrez; J. Niu; S. Siddiqi; X. Li; J. Cyrus; A. Chackerian; A. Chain; R. A. Altura; B. C. Cho

doi:10.1016/j.annonc.2020.11.020

Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

R. Perets, J. Bar, D. W. Rasco, M. J. Ahn, K. Yoh, D. W. Kim, A. Nagrial, M. Satouchi, D. H. Lee, D. R. Spigel, D. Kotasek, M. Gutierrez, J. Niu, S. Siddiqi, X. Li, J. Cyrus, A. Chackerian, A. Chain, R. A. Altura, B. C. Cho

Department of Internal Medicine

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

30 Citations (Scopus)

Abstract

Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.

Original language	English
Pages (from-to)	395-403
Number of pages	9
Journal	Annals of Oncology
Volume	32
Issue number	3
DOIs	https://doi.org/10.1016/j.annonc.2020.11.020
Publication status	Published - 2021 Mar

Bibliographical note

Funding Information:
The authors thank Brent Butts, Jane Guo, Dewan Hossain, Mohini Rajasagi, and Yiwei Zhang from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing and/or editorial assistance were provided by Melanie Sweetlove, MSc, Holly C. Cappelli, PhD, CMPP, and Dana Francis, PhD, of ApotheCom (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Publisher Copyright:
© 2020 The Authors

All Science Journal Classification (ASJC) codes

Hematology
Oncology

UN SDGs

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

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10.1016/j.annonc.2020.11.020

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Perets, R., Bar, J., Rasco, D. W., Ahn, M. J., Yoh, K., Kim, D. W., Nagrial, A., Satouchi, M., Lee, D. H., Spigel, D. R., Kotasek, D., Gutierrez, M., Niu, J., Siddiqi, S., Li, X., Cyrus, J., Chackerian, A., Chain, A., Altura, R. A., & Cho, B. C. (2021). Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. Annals of Oncology, 32(3), 395-403. https://doi.org/10.1016/j.annonc.2020.11.020

@article{c0f2844a931d4d27b591c90f5791bc00,

title = "Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer",

abstract = "Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.",

author = "R. Perets and J. Bar and Rasco, {D. W.} and Ahn, {M. J.} and K. Yoh and Kim, {D. W.} and A. Nagrial and M. Satouchi and Lee, {D. H.} and Spigel, {D. R.} and D. Kotasek and M. Gutierrez and J. Niu and S. Siddiqi and X. Li and J. Cyrus and A. Chackerian and A. Chain and Altura, {R. A.} and Cho, {B. C.}",

note = "Funding Information: The authors thank Brent Butts, Jane Guo, Dewan Hossain, Mohini Rajasagi, and Yiwei Zhang from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing and/or editorial assistance were provided by Melanie Sweetlove, MSc, Holly C. Cappelli, PhD, CMPP, and Dana Francis, PhD, of ApotheCom (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = mar,

doi = "10.1016/j.annonc.2020.11.020",

language = "English",

volume = "32",

pages = "395--403",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "3",

}

Perets, R, Bar, J, Rasco, DW, Ahn, MJ, Yoh, K, Kim, DW, Nagrial, A, Satouchi, M, Lee, DH, Spigel, DR, Kotasek, D, Gutierrez, M, Niu, J, Siddiqi, S, Li, X, Cyrus, J, Chackerian, A, Chain, A, Altura, RA & Cho, BC 2021, 'Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer', Annals of Oncology, vol. 32, no. 3, pp. 395-403. https://doi.org/10.1016/j.annonc.2020.11.020

TY - JOUR

T1 - Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

AU - Perets, R.

AU - Bar, J.

AU - Rasco, D. W.

AU - Ahn, M. J.

AU - Yoh, K.

AU - Kim, D. W.

AU - Nagrial, A.

AU - Satouchi, M.

AU - Lee, D. H.

AU - Spigel, D. R.

AU - Kotasek, D.

AU - Gutierrez, M.

AU - Niu, J.

AU - Siddiqi, S.

AU - Li, X.

AU - Cyrus, J.

AU - Chackerian, A.

AU - Chain, A.

AU - Altura, R. A.

AU - Cho, B. C.

N1 - Funding Information: The authors thank Brent Butts, Jane Guo, Dewan Hossain, Mohini Rajasagi, and Yiwei Zhang from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing and/or editorial assistance were provided by Melanie Sweetlove, MSc, Holly C. Cappelli, PhD, CMPP, and Dana Francis, PhD, of ApotheCom (Yardley, PA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Publisher Copyright: © 2020 The Authors

PY - 2021/3

Y1 - 2021/3

N2 - Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.

AB - Background: Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated in a phase I study. Patients and methods: Dose-escalation (DE) phase: patients with advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 mg (cohort 2), or 200 mg (cohort 3)] followed by four treatments of the same quavonlimab dose plus pembrolizumab every 3 weeks (Q3W). Dose-confirmation phase (DC): patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received first-line quavonlimab [25 mg Q3W (arm A), 25 mg Q6W (arm B), 75 mg Q6W (arm C), or 75 mg Q3W (arm E)] plus pembrolizumab. Primary objectives were safety and tolerability and establishment of the recommended phase II dose (RP2D) of quavonlimab when used with pembrolizumab. Objective response rate (ORR) was a secondary endpoint. Efficacy based on PD-L1 expression, tumor mutational burden (TMB), and changes in circulating CD4+/CD8+ cells were exploratory endpoints. Results: Thirty-nine patients were enrolled in DE [n = 14 (cohort 1); n = 17 (cohort 2); n = 8 (cohort 3)] and 134 in DC [n = 40 (arm A); n = 40 (arm B); n = 40 (arm C); n = 14 (arm E)]. Maximum-tolerated dose was not reached. Grade 3-5 treatment-related adverse events (AEs; graded according to NCI CTCAE v4.03) occurred in 0%, 23.5%, and 75.0% of patients in DE cohorts 1, 2, and 3, respectively, and 35.0%, 30.0%, 35.0%, and 57.1% of patients in DC arms A, B, C, and E, respectively. Efficacy was observed at all dose levels/schedules in patients with NSCLC. ORRs were 40.0% [95% confidence interval (CI), 24.9-56.7; arm A], 37.5% (95% CI, 22.7-54.2; arm B), 27.5% (95% CI, 14.6-43.9; arm C), and 35.7% (95% CI, 12.8-64.9; arm E). PD-L1 expression and total number of circulating CD4+ cells correlated with ORR. Conclusions: Quavonlimab 25 mg Q6W plus pembrolizumab demonstrated similar efficacy and a better safety profile among all quavonlimab doses/schedules evaluated; this regimen was the chosen RP2D.

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Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer

Abstract

Bibliographical note

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UN SDGs

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