Evidence map›Paper›PMID 37016126›Full record

ArticleCancer immunology, immunotherapy : CII2023

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.

Johanna Bendell, Patricia LoRusso, Michael Overman, Anne M Noonan, Dong-Wan Kim, John H Strickler, Sang-We Kim, Stephen Clarke, Thomas J George, Peter S Grimison and 14 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02503774 (A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors), which is not on this map. Cited by 93 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 1 pooled it
24.0field-weighted citation impact, top 1% 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.

NCT02503774 phase1completednot on this map

A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI9447 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

TypeinterventionalSponsorMedImmune LLCRan2015 to 2023Enrolled192ConditionsSolid TumorsArmsOleclumab, Durvalumab
3 · Its place in the literature

Who cites it

93 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

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33 more citing papers are in PubMed but not listed here.

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

24 authors at 16 institutions in 4 countries.

Johanna BendellSarah Cannon Research Institute, Nashville, TN, USA. Johanna.bendell@roche.com.
Patricia LoRussoYale University Cancer Center, New Haven, CT, USA.
Michael OvermanUniversity of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5377-135X
Anne M NoonanOhio State University, Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA.ORCID http://orcid.org/0000-0001-8083-8492
Dong-Wan KimSeoul National University Hospital, Seoul, South Korea.ORCID http://orcid.org/0000-0001-5124-7132
John H StricklerDuke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0001-7579-1175
Sang-We KimAsan Medical Center, Seoul, South Korea.
Stephen ClarkeRoyal North Shore Hospital, St. Leonards, NSW, Australia.
Thomas J GeorgeUniversity of Florida Health Cancer Center, Gainesville, FL, USA.ORCID http://orcid.org/0000-0002-6249-9180
Peter S GrimisonChris O'Brien Lifehouse, Camperdown, NSW, Australia.ORCID http://orcid.org/0000-0002-2653-1657
Minal BarveMary Crowley Cancer Research, Dallas, TX, USA.
Manik AminWashington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-8467-6152
Jayesh DesaiRoyal Melbourne Hospital, Parkville, VIC, Australia.
Trisha Wise-DraperUniversity of Cincinnati Cancer Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-7279-4028
Steven EckAstraZeneca, Gaithersburg, MD, USA.
Yu JiangAstraZeneca, Gaithersburg, MD, USA.
Anis A KhanAstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0001-8262-3022
Yuling WuAstraZeneca, Gaithersburg, MD, USA.
Philip MartinAstraZeneca, Gaithersburg, MD, USA.
Zachary A CooperAstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0003-1059-0940
Nairouz ElgeioushiAstraZeneca, Gaithersburg, MD, USA.
Nancy MuellerAstraZeneca, Gaithersburg, MD, USA.
Rakesh KumarAstraZeneca, Gaithersburg, MD, USA.ORCID http://orcid.org/0000-0002-4627-3667
Sandip Pravin PatelMoores Cancer Center, University of California San Diego, La Jolla, San Diego, CA, USA.
AstraZeneca (United States) · USAsan Medical Center · KRChris O’Brien Lifehouse · AUDartmouth–Hitchcock Medical Center · USDuke Medical Center · USMary Crowley Cancer Research Center · USRoche (Switzerland) · CHRoyal North Shore Hospital · AUSeoul National University Hospital · KRThe Ohio State University Wexner Medical Center · USThe Royal Melbourne Hospital · AUThe University of Texas MD Anderson Cancer Center · USUniversity of California San Diego · USUniversity of Cincinnati · USUniversity of Florida Health · USYale Cancer Center · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
NCATS NIH HHS UL1 TR001863
6 · The paper itself

Abstract

backgroundCD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC).

methodsPatients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W.

results192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively; the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively; 6-month progression-free survival rates were 5.4, 13.2, and 16.0%.

conclusionsOleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. CLINICAL

trial registrationClinicaltrials.gov, NCT02503774; date of registration, July 17, 2015.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungLung NeoplasmsAntibodies, MonoclonalFatigueHumansAntibodies, MonoclonalAntineoplastic AgentsdurvalumabAdenosineCD73Monoclonal antibodyOleclumabTumor microenvironment

Identifiers

PMID37016126
PMCPMC10264501
OpenAlexW4362526763

What OpenQuestion holds

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LicenceCC BY
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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.