A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non-Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1.
Adult
Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Antibodies, Monoclonal
/ administration & dosage
Antineoplastic Agents, Immunological
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Carcinoma, Renal Cell
/ drug therapy
Drug Combinations
Drug Resistance, Neoplasm
Immune Checkpoint Inhibitors
/ therapeutic use
Kidney Neoplasms
/ drug therapy
Lung Neoplasms
/ drug therapy
Melanoma
/ drug therapy
Nivolumab
/ administration & dosage
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
10
03
2021
revised:
03
05
2021
accepted:
14
06
2021
pubmed:
19
6
2021
medline:
5
4
2022
entrez:
18
6
2021
Statut:
ppublish
Résumé
PD-1/PD-L1 inhibitors are approved for multiple tumor types. However, resistance poses substantial clinical challenges. We conducted a phase I trial of CD40 agonist APX005M (sotigalimab) and CSF1R inhibitor cabiralizumab with or without nivolumab using a 3+3 dose-escalation design (NCT03502330). Patients were enrolled from June 2018 to April 2019. Eligibility included patients with biopsy-proven advanced melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC) who progressed on anti-PD-1/PD-L1. APX005M was dose escalated (0.03, 0.1, or 0.3 mg/kg i.v.) with a fixed dose of cabiralizumab with or without nivolumab every 2 weeks until disease progression or intolerable toxicity. Twenty-six patients (12 melanoma, 1 NSCLC, and 13 RCC) were enrolled in six cohorts, 17 on nivolumab-containing regimens. Median duration of follow-up was 21.3 months. The most common treatment-related adverse events were asymptomatic elevations of lactate dehydrogenase ( This first in-human study of patients with anti-PD-1/PD-L1-resistant tumors treated with dual macrophage-polarizing therapy, with or without nivolumab demonstrated safety and pharmacodynamic activity. Optimization of the dosing frequency and sequence of this combination is warranted.
Identifiants
pubmed: 34140403
pii: 1078-0432.CCR-21-0903
doi: 10.1158/1078-0432.CCR-21-0903
pmc: PMC9236708
mid: NIHMS1812084
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
Drug Combinations
0
Immune Checkpoint Inhibitors
0
Nivolumab
31YO63LBSN
sotigalimab
0
cabiralizumab
0
Banques de données
ClinicalTrials.gov
['NCT03502330']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4757-4767Subventions
Organisme : NCI NIH HHS
ID : R01 CA227473
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA215110
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA216846
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA121974
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014195
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA196530
Pays : United States
Informations de copyright
©2021 American Association for Cancer Research.
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