Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00079064" target="_blank" >RIV/00209805:_____/22:00079064 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S2059702922001909?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2059702922001909?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.esmoop.2022.100562" target="_blank" >10.1016/j.esmoop.2022.100562</a>

Result language

angličtina

Original language name

Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study

Original language description

Background: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon&apos;s two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). Results: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced GREATER-THAN OR EQUAL TO1 treatment-emergent adverse event (TEAE), with LESS-THAN OR EQUAL TO48.5% being grade GREATER-THAN OR EQUAL TO3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. Conclusions: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30204 - Oncology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

ESMO open

ISSN

2059-7029

e-ISSN

2059-7029

Volume of the periodical

7

Issue of the periodical within the volume

5

Country of publishing house

GB - UNITED KINGDOM

Number of pages

8

Pages from-to

100562

UT code for WoS article

000861347400006

EID of the result in the Scopus database

2-s2.0-85136683326