Abstrakti
Background: Budigalimab is a humanized, recombinant immunoglobulin G1 monoclonal antibody targeting programmed cell death protein 1 (PD-1). We present the safety, efficacy, pharmacokinetic (PK), and pharmacodynamic data from patients enrolled in the head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) expansion cohorts of the phase 1 first-in-human study of budigalimab monotherapy (NCT03000257; registered 15 December 2016). Patients and methods: Patients with recurrent/metastatic HNSCC or locally advanced/metastatic NSCLC naive to PD-1/PD-1-ligand inhibitors were enrolled; patients were not selected on the basis of oncogene driver mutations or PD-L1 status. Budigalimab was administered at 250 mg intravenously Q2W or 500 mg intravenously Q4W until disease progression/unacceptable toxicity. The primary endpoints were safety and PK; the secondary endpoint was efficacy. Exploratory endpoints included biomarker assessments. Results: In total, 81 patients were enrolled (HNSCC: N = 41 [PD-L1 positive: n = 19]; NSCLC: N = 40 [PD-L1 positive: n = 16]); median treatment duration was 72 days (range, 1–617) and 71 days (range, 1–490) for the HNSCC and NSCLC cohorts, respectively. The most frequent grade ≥ 3 treatment-emergent adverse event was anemia (HNSCC: n = 9, 22%; NSCLC: n = 5, 13%). Both dosing regimens had comparable drug exposure and increased interferon gamma-induced chemokines, monokine induced by gamma interferon, and interferon-gamma-inducible protein 10. Objective response rates were 13% (90% CI, 5.1–24.5) in the HNSCC cohort and 19% (90% CI, 9.2–32.6) in the NSCLC cohort. Median progression-free survival was 3.6 months (95% CI, 1.7–4.7) and 1.9 months (95% CI, 1.7–3.7) in the HNSCC and NSCLC cohorts. Conclusions: The safety, efficacy and biomarker profiles of budigalimab are similar to other PD-1 inhibitors. Development of budigalimab in combination with novel anticancer agents is ongoing.
| Alkuperäiskieli | englanti |
|---|---|
| Lehti | Cancer Immunology, Immunotherapy |
| Vuosikerta | 71 |
| Numero | 2 |
| Sivut | 417-431 |
| Sivumäärä | 15 |
| ISSN | 0340-7004 |
| DOI - pysyväislinkit | |
| Tila | Julkaistu - helmik. 2022 |
| OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu |
Lisätietoja
Funding Information:AbbVie and the authors thank the patients who participated in this clinical trial, the study coordinators, and support staff. We would like to acknowledge James P. Sheridan (Drug Metabolism Pharmacokinetics & Bioanalysis Department, AbbVie) for performing the preclinical and clinical pharmacokinetic studies, and Fiona Harding (Oncology Discovery, AbbVie) for creating, selecting, and validating the ABBV-181 antibody and filing the in vitro/in vivo IND supporting reports, including summaries of the preclinical activity of ABBV-181. Biomarker sample testing was performed by Covance, Princeton, NJ (flow cytometry), Mosaic Laboratories, Lake Forest, CA (immunohistochemistry), and Myriad RBM, Austin, TX (cytokine testing). This study was funded by AbbVie Inc., North Chicago, IL, USA. Medical writing support was provided by Joanne Franklin, PhD, CMPP, Aptitude Health, The Hague, the Netherlands, funded by AbbVie.
Funding Information:
AbbVie and the authors thank the patients who participated in this clinical trial, the study coordinators, and support staff. We would like to acknowledge James P. Sheridan (Drug Metabolism Pharmacokinetics & Bioanalysis Department, AbbVie) for performing the preclinical and clinical pharmacokinetic studies, and Fiona Harding (Oncology Discovery, AbbVie) for creating, selecting, and validating the ABBV-181 antibody and filing the in vitro/in vivo IND supporting reports, including summaries of the preclinical activity of ABBV-181. Biomarker sample testing was performed by Covance, Princeton, NJ (flow cytometry), Mosaic Laboratories, Lake Forest, CA (immunohistochemistry), and Myriad RBM, Austin, TX (cytokine testing). This study was funded by AbbVie Inc., North Chicago, IL, USA. Medical writing support was provided by Joanne Franklin, PhD, CMPP, Aptitude Health, The Hague, the Netherlands, funded by AbbVie.
Funding Information:
Antoine Italiano: Consulting/advisory role: Roche, Daiichi Sankyo, Immune Design, Epizyme, Bayer, Lilly; honoraria: Bayer, Daiichi Sankyo, Lilly, Epizyme, Novartis, Roche; research funding: Roche, Bayer, AstraZeneca/MedImmune, PharmaMar, MSD Oncology, Merck Serono. Philippe A. Cassier: Honoraria: Novartis, Roche/Genentech, Blueprint Medicines, Amgen; research funding: Novartis, Roche/Genentech, Lilly, Blueprint Medicines, Bayer, AstraZeneca, Celgene, Plexxikon, AbbVie, Bristol-Myers Squibb, Merck Serono, Merck Sharp & Dohme; Consultancy/advisory role: Merck Serono, Roche/Genentech. Chia-Chi Lin: Consulting/advisory role: Novartis, Boehringer Ingelheim, Blueprint Medicines; travel/accommodations/expenses: Lilly, Daiichi Sankyo, BeiGene, Novartis; honoraria: Novartis, Roche, Daiichi Sankyo. Tuomo Alanko: Consulting/advisory role: Bayer, Baxalta/Shire, BMS, Celgene, Eli Lilly, MSD, Nordic Drugs, Roche, Kaiku Health; research funding: AbbVie, Bayer, Boehringer Ingelheim, BMS, Debiopharm, Eli Lilly, Incyte, MSD, Pfizer, Roche; travel/accommodations/expenses: Baxalta/Shire, BMS, MSD, Pfizer, Roche. Katriina J. Peltola: Consulting/advisory role: Orion Pharma, BMS, MSD, Novartis, Pfizer, Ipsen, Roche, Varian; stockholder: Faron Pharmaceuticals; speakers’ bureau: BMS, Pfizer, MSD; expert testimony: Ipsen; travel/accommodations/expenses: Roche, BMS; research funding: AbbVie, Bayer, BMS, MSD, Roche, Exelixis, Orion Pharma, Eisai, Novartis. Anas Gazzah: Travel, accommodations, congress registration expenses: Boehringer Ingelheim, Novartis, Pfizer, Roche; consultant/expert role: Novartis; principal/sub-investigator of clinical trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X BVBA, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca, Aveo, Bayer HealthCare Ag, BBB Technologies BV, BeiGene, BioAlliance Pharma, BioNTech AG, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm SA, Eisai, Exelixis, Forma, GamaMabs, Genentech, Inc., Gilead Sciences, Inc, GlaxoSmithKline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, F. Hoffmann-La Roche AG, Incyte Corporation, Innate Pharma, Servier IRIS, Janssen, Kura Oncology, Kyowa Kirin Pharmaceutical Development, Lilly, Loxo Oncology, Lytix Biopharma AS, MedImmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology NV, OncoEthix, OncoMed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, PharmaMar, Pierre Fabre, Rigontec GmbH, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Inc, Tioma Therapeutics, Inc., Xencor; research grants: AstraZeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; nonfinancial support (drug supplied): AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, MedImmune, Merck, NH TherAGuix, Pfizer, Roche. Her-Shyong Shiah: The author declares no potential conflicts of interest. Emiliano Calvo: Consulting/advisory role: Novartis, Nanobiotix, Janssen-Cilag, PsiOxus, Seattle Genetics, EUSA Pharma, AbbVie, Celgene, AstraZeneca, Guidepoint Global, Roche/Genentech, GLG, Pfizer, Servier, amcure; speakers’ bureau: Novartis; research funding: AstraZeneca, BeiGene, Novartis, START; travel/accommodations/expenses reimbursement: Roche/Genentech; honoraria: HM Hospitales Group; stock/ownership interests: START, Oncoart Associated, International Cancer Consultants; president and founder of Foundation INTHEOS . Andrés Cervantes: Institutional research funding: AbbVie, Genentech, Merck Serono, BMS, MSD, Roche, BeiGene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, FibroGen; advisory board or speaker fees: Merck Serono, Roche, Bayer, Servier, Pierre Fabre. Desamparados Roda: The author declares no potential conflicts of interest. Diego Tosi: Consulting/advisory role: BioMarin (immediate family member); research funding: Novartis, Astellas, Janssen; patent pending on a new drug combination for prostate cancer treatment; travel/accommodations/expenses: Janssen, Pfizer, Astellas Pharma; immediate family member had travel/accommodations/expenses from Nutricia and Amicus. Bo Gao: Consulting/advisory role: MSD. Michael Millward: Consulting/advisory role: Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Roche, Pfizer, Takeda, Novartis; conference travel/support: Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Roche. Lydia Warburton: Travel/accommodations/expenses: MSD, Merck. Minna Tanner: Consulting/advisory role: Roche, Novartis, Pfizer; speakers’ bureau: Roche, Novartis, Pfizer, Amgen. Gregory Vosganian: Former employee of AbbVie and may own stock. Stefan Englert, Stacie Lambert, Apurvasena Parikh, Daniel E. Afar: AbbVie employees and may own stock. Victor Moreno: Consulting fees: Merck, BMS, Janssen, Pieris; travel/accommodations: Regeneron/Sanofi; presentations: Nanobiotix; educational grant: Medscape/Bayer.
Publisher Copyright:
© 2021, The Author(s).
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