First-in-human phase 1 study of budigalimab, an anti-PD-1 inhibitor, in patients with non-small cell lung cancer and head and neck squamous cell carcinoma

Antoine Italiano, Philippe A Cassier, Chia-Chi Lin, Tuomo Alanko, Katriina J Peltola, Anas Gazzah, Her-Shyong Shiah, Emiliano Calvo, Andrés Cervantes, Desamparados Roda, Diego Tosi, Bo Gao, Michael Millward, Lydia Warburton, Minna Tanner, Stefan Englert, Stacie Lambert, Apurvasena Parikh, Daniel E Afar, Gregory Vosganian, Victor Moreno, Antoine Italiano, Philippe A Cassier, Chia-Chi Lin, Tuomo Alanko, Katriina J Peltola, Anas Gazzah, Her-Shyong Shiah, Emiliano Calvo, Andrés Cervantes, Desamparados Roda, Diego Tosi, Bo Gao, Michael Millward, Lydia Warburton, Minna Tanner, Stefan Englert, Stacie Lambert, Apurvasena Parikh, Daniel E Afar, Gregory Vosganian, Victor Moreno

Abstract

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.

Keywords: Budigalimab; Head and neck squamous cell cancer; Non-small cell lung cancer; PD-1 inhibitor.

Conflict of interest statement

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.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
PD-1 receptor saturation and pharmacodynamic effects of budigalimab administration by dose level. Data shown for each patient with assay baseline and at least 1 postbaseline value. Individual patient data shown for patients with ≥ twofold change in CD8 Ki67 staining. Mean + /– 95% CI shown for PD-1 staining, T-cell counts, and cytokines (number of patients for each mean shown in graph). C, cycle; D, day; HNSCC, head and neck squamous cell carcinoma; hr, hour; IP-10, interferon gamma-induced protein 10; mAb, monoclonal antibody; MIG, monokine induced by gamma interferon; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; Q, every; TCM, central memory T cells; W, weeks
Fig. 2
Fig. 2
Best percentage change in target lesions from baseline for a HNSCC and b NSCLC cohorts receiving budigalimab monotherapy. aPD-L1 + status; bPD-L1 status missing (i.e., unknown). ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small cell lung cancer; PD-L1 + , programmed cell death protein 1 ligand 1 positive; Q, every; W, weeks
Fig. 3
Fig. 3
Percentage change in target lesions from baseline for a HNSCC and b NSCLC cohorts receiving budigalimab monotherapy. ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; HNSCC, head and neck squamous cell carcinoma; NSCLC, non-small cell lung V; PD-1, programmed cell death protein 1; Q, every; W, weeks

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