Evidence map›Paper›PMID 35987165›Full record

Trial reportESMO open2022

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

M Simonelli, E Garralda, F Eskens, M Gil-Martin, C-J Yen, R Obermannova, Y Chao, S Lonardi, B Melichar, V Moreno and 22 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03637764 (A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03637764 phase1 / phase2terminatednot on this map

A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab (SAR650984) in Combination With Atezolizumab or Isatuximab Alone in Patients With Advanced Malignancies

TypeinterventionalSponsorSanofiRan2018 to 2022Enrolled107ConditionsNeoplasmArmsIsatuximab SAR650984, Atezolizumab
3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

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  9. Targeting T regulatory (TCancer drug resistance (Alhambra, Calif.) · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors at 20 institutions in 9 countries.

M SimonelliIRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. Electronic address: matteo.simonelli@hunimed.eu.
E GarraldaVall d'Hebron Institute of Oncology, Barcelona, Spain.
F EskensErasmus MC Cancer Institute, Rotterdam, the Netherlands.
M Gil-MartinInstitut Català d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain.
C-J YenNational Cheng Kung University, Tainan, Taiwan.
R ObermannovaMasaryk Memorial Cancer Institute, Brno, Czech Republic.
Y ChaoDepartment of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
S LonardiVeneto Institute of Oncology IOV, IRCCS, Padova, Italy.
B MelicharDepartment of Oncology, Palacky University, Olomouc, Czech Republic.
V MorenoSTART Madrid-FJD, Hospital Fundación Jiménez Díaz, Madrid, Spain.
M-L YuHepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
A BongiovanniIRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
E CalvoSTART Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain.
S RotteyGhent University, Ghent.
J-P MachielsCliniques Universitaires Saint-Luc, Brussels, Belgium.
A Gonzalez-MartinClínica Universidad de Navarra, Madrid, and Program in Solid Tumors, Center for Applied Medical Research (CIMA), Pamplona.
L Paz-AresHospital Universitario 12 de Octubre, Madrid, Spain.
C-L ChangDepartment of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
W MasonPrincess Margaret Cancer Centre, Toronto, Canada.
C-C LinNational Taiwan University Hospital, Taipei, Taiwan.
D A ReardonDana-Farber Cancer Institute, Harvard University, Boston.
M VieitoVall d'Hebron Institute of Oncology, Barcelona, Spain.
A SantoroDepartment of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy; Vall d'Hebron Institute of Oncology, Barcelona, Spain.
R MengSanofi, Cambridge, USA.
G AbbadessaSanofi, Cambridge, USA.
F MenasSanofi, Chilly-Mazarin, France.
H LeeSanofi, Cambridge, USA.
Q LiuSanofi, Cambridge, USA.
C CombeauSanofi, Chilly-Mazarin, France.
N TernesSanofi, Chilly-Mazarin, France.
S Ziti-LjajicSanofi, Chilly-Mazarin, France.
C MassardGustave Roussy, Villejuif, France.
Sanofi (France) · FRSanofi (United States) · USHumanitas University · ITVall d'Hebron Institute of Oncology · ESClinica Universidad de Navarra · ESCliniques Universitaires Saint-Luc · BEErasmus MC Cancer Institute · NLGhent University Hospital · BEHarvard University · USHospital Universitario 12 De Octubre · ESHospital Universitario Fundación Jiménez Díaz · ESInstitut d'Investigació Biomédica de Bellvitge · ESInstitut Gustave Roussy · FRIstituto Oncologico Veneto · ITIstituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori · ITKaohsiung Medical University · TWMackay Memorial Hospital · TWMasaryk Memorial Cancer Institute · CZNational Cheng Kung University · TWNational Taiwan University Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe 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

methodsPhase 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'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).

resultsOverall, 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 ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. 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.

conclusionsIsa + 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.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsAntibodies, Monoclonal, HumanizedB7-H1 AntigenForkhead Transcription FactorsHumansTumor MicroenvironmentAntibodies, Monoclonal, HumanizedatezolizumabB7-H1 AntigenForkhead Transcription Factorsisatuximabanti-CD38anti-PD-L1atezolizumabisatuximabsolid tumors

Identifiers

PMID35987165
PMCPMC9588873
OpenAlexW4292411599

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.