Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep 11:16:17588359241274592.
doi: 10.1177/17588359241274592. eCollection 2024.

Pharmacokinetics, safety, and efficacy of an alternative dosing regimen of sasanlimab in participants with advanced NSCLC and other malignancies

Konstantin Penkov  1 , Igor Bondarenko  2 , Daria Viktorovna Saenko  3 , Yaroslav Kulyaba  4 , Jun Guo  5 , Yi Gong  6 , Noboru Yamamoto  7 , Yevhen Stepanovych Hotko  8 , Vasyl Boyko  9 , Natalya Vladimirovna Fadeeva  10 , Grygorii Mykolaiovych Ursol  11 , Hee Kyung Ahn  12 , Nikolay Viktorovich Kislov  13 , Chia-I Shen  14 , Craig Davis  15 , Karey Kowalski  15 , Elisabete Michelon  16 , Dmitri Pavlov  15 , Tomoko Hirohashi  17 , Byoung Chul Cho  18
Affiliations

Pharmacokinetics, safety, and efficacy of an alternative dosing regimen of sasanlimab in participants with advanced NSCLC and other malignancies

Konstantin Penkov et al. Ther Adv Med Oncol. .

Abstract

Background: Sasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction.

Objectives: To evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens.

Design: An open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies.

Phase ii: conducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W).

Methods: Primary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC.

Results: A total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUCtau was 231.2 (90% CI, 190.1-281.2) and C trough was 111.5 (90% CI, 86.3-144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2-42.9)) and 12/80 (15.0% (95% CI, 8.0-24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively.

Conclusions: Phase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUCtau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration.

Trial registration: NCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT).

Keywords: immune checkpoint inhibitor; immunotherapy; lung neoplasms; non-small-cell lung cancer; programmed cell death 1 receptor.

PubMed Disclaimer

Conflict of interest statement

KP reports grants or contracts from Novartis, AstraZenica, Beigene, Regeneron, Janssen, Pfizer. JG reports consultancy/advisory for Merck Sharp & Dohme, Roche, Bayer, Novartis, Simcere Pharmaceutical Group, Shanghai Junshi Biosciences, Oriengene. NY reports research grant as PI from Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin’ Takeda, ONO, Janssen Pharma, MSD, MERCK, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic, InventisBio, Rakuten Medical; consulting fees for Eisai, Takeda, Boehringer Ingelheim, Cmic, Chugai, MERCK, Healios; honoraria as speaker for ONO, Chugai, Daiichi Sankyo, Eisa. HKA reports consulting fees for Bayer and honoraria for lectures from Roche, Bristol Myers Squibb, MSD, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Yuhan, Eisai, Pfizer, Boryung Pharmaceutical Co, Menarini, Takeda, Novartis, Amgen, Celltrion, Daiichi Sankyo. NK reports provision of study materials, review and corrections as PI on current manuscript; contracted research for AstraZeneca, EMD Serono, Genentech/Roche, MSD, GSK, Ipsen, Novartis, Pfizer, Nektar, Lilly; honoraria for lectures for Biocad, AstraZeneca, Janssen; meetings support for Biocad, AstraZeneca. CIS reports medical writing support and article processing charges on present manuscript, honoraria for lectures, presentations, speakers from Pfizer, Boehringer Ingelheim, Lilly, Janssen, Takeda, Novartis, Merck Sharp & Dohme, Amgen, AstraZeneca, Roche, Chugai Pharmaceutical Co; attending meetings for Takeda, Boehringer Ingelheim. KK reports employment by and financial grants from Pfizer; travel and meeting funds from Pfizer; patient inventor or author for Pfizer; stock/shares in Pfizer. BCC reports research funding from MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, Abbvie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, J INTS bio, Hanmi, CHA Bundang Medical Center; royalties from Champions Oncology, Crown Bioscience, Imagen; advisory/consultancy roles for Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi; presentations for ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Medical Onoclogy, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer; scientific advisory board for KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; member on board of directors for Interpark Bio Convergence Corp., J INTS BIO; stock/shares in TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; employment by Yonsei University Health System; and being the founder of DAAN Biotherapeutics. DP reports employment with Pfizer. CD, EM, TH report employment with Pfizer and hold stock/shares in Pfizer. IB, DVS, YK, YG, YSH, VB, NVF, GMU have nothing to disclose.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Study design. Phase Ib population: Asian participants with advanced solid tumors; phase II population: global participants with first-line or second-line NSCLC. Phase Ib and phase II were conducted in parallel. DLT, dose-limiting toxicity; NSCLC, non-small-cell lung cancer; Q4W, every 4 weeks; Q6W, every 6 weeks; SC, subcutaneous.
See this image and copyright information in PMC

References

    1. Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 2018; 18: 153–167. - PubMed
    1. Zheng Y, Fang YC, Li J. PD-L1 expression levels on tumor cells affect their immunosuppressive activity. Oncol Lett 2019; 18: 5399–5407. - PMC - PubMed
    1. Wang D-R, Wu X-L, Sun Y-L. Therapeutic targets and biomarkers of tumor immunotherapy: a response versus non-response. Signal Transduct Target Ther 2022; 7: 331. - PMC - PubMed
    1. Freeman GJ, Long AJ, Iwai Y, et al.. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192: 1027–1034. - PMC - PubMed
    1. Bedke J, Black PC, Szabados B, et al.. Optimizing outcomes for high-risk, non-muscle-invasive bladder cancer: The evolving role of PD-(L)1 inhibition. Urologic Oncology: Seminars and Original Investigations 2023; 41: 461–475. - PubMed

Associated data

LinkOut - more resources