Evidence map›Paper›PMID 37385724›Full record

ArticleJournal for immunotherapy of cancer2023

Phase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas.

Andrew L Coveler, David C Smith, Tycel Phillips, Brendan D Curti, Sanjay Goel, Amitkumar N Mehta, Timothy M Kuzel, Svetomir N Markovic, Olivier Rixe, David L Bajor and 13 more

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

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02376699 (A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 8% 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.

NCT02376699 phase1terminatednot on this map

A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies

TypeinterventionalSponsorSeagen Inc.Ran2015 to 2023Enrolled159ConditionsCarcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Hodgkin Disease, LymphomaArmsIntravenous (IV) SEA-CD40, Pembrolizumab, Subcutaneous (SC) SEA-CD40, Gemcitabine, Nab-paclitaxel
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
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  14. Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
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  18. Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 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

23 authors at 15 institutions in 1 country.

Andrew L CovelerFred Hutchinson Cancer Center, Seattle, Washington, USA acoveler@uw.edu.ORCID 0000-0003-1710-5637
David C SmithUniversity of Michigan, Ann Arbor, Michigan, USA.
Tycel PhillipsUniversity of Michigan, Ann Arbor, Michigan, USA.
Brendan D CurtiProvidence Cancer Center, Portland, Oregon, USA.ORCID 0000-0003-3948-2708
Sanjay GoelMontefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0002-2798-7568
Amitkumar N MehtaThe University of Alabama, Birmingham, Alabama, USA.
Timothy M KuzelRush University Medical Center, Chicago, Illinois, USA.
Svetomir N MarkovicMayo Clinic Minnesota, Rochester, Minnesota, USA.
Olivier RixeThe University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA.
David L BajorCase Western Reserve University, Cleveland, Ohio, USA.
Thomas F GajewskiThe University of Chicago Medical Center, Chicago, Illinois, USA.
Martin GutierrezHackensack University Medical Center, Hackensack, New Jersey, USA.
Hun Ju LeeThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ajay K GopalFred Hutchinson Cancer Center, Seattle, Washington, USA.
Paolo CaimiCase Western Reserve University, Cleveland, Ohio, USA.
Elisabeth I HeathBarbara Ann Karmanos Cancer Institute, Detroit, Michigan, USA.
John A ThompsonFred Hutchinson Cancer Center, Seattle, Washington, USA.
Sahar AnsariSeagen Inc, Bothell, Washington, USA.
Celine JacquemontSeagen Inc, Bothell, Washington, USA.
Ariel Topletz-EricksonSeagen Inc, Bothell, Washington, USA.
Peigen ZhouSeagen Inc, Bothell, Washington, USA.
Michael W SchmittSeagen Inc, Bothell, Washington, USA.
Juneko E Grilley-OlsonDuke Cancer Institute, Durham, North Carolina, USA.
Seagen (United States) · USUniversity of Washington · USUniversity Hospitals of Cleveland · USUniversity of Michigan · USAlbert Einstein College of Medicine · USDuke University · USHackensack University Medical Center · USMayo Clinic · USProvidence Portland Medical Center · USRush University Medical Center · USThe Barbara Ann Karmanos Cancer Institute · USThe University of Texas MD Anderson Cancer Center · USUniversity of Alabama at Birmingham · USUniversity of Chicago Medical Center · USUniversity of New Mexico · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSEA-CD40 is an investigational, non-fucosylated, humanized monoclonal IgG

methodsSEA-CD40 was administered intravenously to patients with solid tumors or lymphoma in 21-day cycles with standard 3+3 dose escalation at 0.6, 3, 10, 30, 45, and 60 µg/kg. An intensified dosing regimen was also studied. The primary objectives of the study were to evaluate the safety and tolerability and identify the maximum tolerated dose of SEA-CD40. Secondary objectives included evaluation of the pharmacokinetic parameters, antitherapeutic antibodies, pharmacodynamic effects and biomarker response, and antitumor activity.

resultsA total of 67 patients received SEA-CD40 including 56 patients with solid tumors and 11 patients with lymphoma. A manageable safety profile was observed, with predominant adverse events of infusion/hypersensitivity reactions (IHRs) reported in 73% of patients. IHRs were primarily ≤grade 2 with an incidence associated with infusion rate. To mitigate IHRs, a standardized infusion approach was implemented with routine premedication and a slowed infusion rate. SEA-CD40 infusion resulted in potent immune activation, illustrated by dose dependent cytokine induction with associated activation and trafficking of innate and adaptive immune cells. Results suggested that doses of 10-30 µg/kg may result in optimal immune activation. SEA-CD40 monotherapy exhibited evidence of antitumor activity, with a partial response in a patient with basal cell carcinoma and a complete response in a patient with follicular lymphoma.

conclusionsSEA-CD40 was tolerable as monotherapy and induced potent dose dependent immune cell activation and trafficking consistent with immune activation. Evidence of monotherapy antitumor activity was observed in patients with solid tumors and lymphoma. Further evaluation of SEA-CD40 is warranted, potentially as a component of a combination regimen. TRIAL REGISTRATION NUMBER: NCT02376699.

Indexed as

Antineoplastic AgentsBasal Cell CarcinomaLymphoma, FollicularSkin NeoplasmsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCD40 AntigensHumansAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCD40 Antigensantibodies, neoplasmhead and neck neoplasmsimmunotherapylung neoplasms

Identifiers

PMID37385724
PMCPMC10314623
OpenAlexW4382601146

What OpenQuestion holds

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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.