Evidence map›Paper›PMID 34288257›Full record

ArticleThe oncologist2021

First-In-Human, First-In-Class, Phase I Trial of the Fucosylation Inhibitor SGN-2FF in Patients with Advanced Solid Tumors.

Khanh T Do, Laura Quan Man Chow, Karen Reckamp, Rachel E Sanborn, Howard Burris, Francisco Robert, D Ross Camidge, Conor E Steuer, John H Strickler, Amy Weise and 6 more

Open access · bronzeAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.5field-weighted citation impact, top 17% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 36 citations in OpenAlex.

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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

16 authors at 13 institutions in 1 country.

Khanh T DoDana-Farber Cancer Institute, Boston, Massachusetts, USA.ORCID 0000-0002-9411-8899
Laura Quan Man ChowUniversity of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA.
Karen ReckampCity of Hope Comprehensive Cancer Center, Duarte, California, USA.
Rachel E SanbornEarle A. Chiles Research Institute, Providence Cancer Institute, Portland, Oregon, USA.
Howard BurrisSarah Cannon Research Institute, Nashville, Tennessee, USA.
Francisco RobertUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.
D Ross CamidgeUniversity of Colorado Cancer Center, Aurora, Colorado, USA.
Conor E SteuerWinship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA.
John H StricklerDuke University Medical Center, Durham, North Carolina, USA.
Amy WeiseKarmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA.
Jennifer M SpechtUniversity of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA.
Martin GutierrezHackensack University Medical Center, Hackensack, New Jersey, USA.
Peter HaughneySeagen Inc., Bothell, Washington, USA.
Shawna HengelSeagen Inc., Bothell, Washington, USA.
Christina Louise DerlethSeagen Inc., Bothell, Washington, USA.
Timothy A YapThe University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Seagen (United States) · USSeattle Cancer Care Alliance · USCity of Hope · USDana-Farber Cancer Institute · USDuke Medical Center · USEmory University · USHackensack University Medical Center · USProvidence Portland Medical Center · USSarah Cannon · USThe University of Texas MD Anderson Cancer Center · USUniversity of Alabama at Birmingham · USUniversity of Colorado Cancer Center · USWayne State University · US

Funding

Convalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3M
NCATS NIH HHS UL1 TR003167
6 · The paper itself

Abstract

lessons learnedInhibition of glycoprotein fucosylation, as monotherapy and in combination with immune checkpoint blockade, is a promising therapeutic strategy for treating a broad range of cancers. In this first-in-human, first-in-class, phase I study in advanced solid tumors, SGN-2FF demonstrated dose-proportional pharmacokinetics, evidence of pharmacodynamic target inhibition of glycoprotein fucosylation, and preliminary antitumor activity. SGN-2FF was associated with thromboembolic events that led to study termination.

backgroundWe conducted a first-in-human, first-in-class, phase I study of SGN-2FF, a potent small-molecule inhibitor of glycoprotein fucosylation, in patients with advanced solid tumors.

methodsThe study consisted of four parts: SGN-2FF monotherapy dose-escalation (part A) and expansion (part B), and SGN-2FF + pembrolizumab dose-escalation (part C) and expansion (part D). The objectives were to evaluate safety and tolerability, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of SGN-2FF monotherapy and SGN-2FF + pembrolizumab.

resultsForty-six patients were enrolled (part A, n = 33; part B, n = 6; part C, n = 7; part D did not enroll any patients). During part A (n = 32) exploring 1-15 g once daily (QD) and 2-5 g twice daily (b.i.d.), grade 3 dose-limiting toxicities were diarrhea (2 g and 15 g QD) and increased lipase (2 g QD). The MTD was 10 g daily. In part A, common toxicities were grades 1-2 diarrhea, fatigue, and nausea (each 47%); thromboembolic events (grades 2-5) occurred in 5 of 32 patients (16%). Safety measures included concurrent prophylactic anticoagulation with low-molecular weight heparin (LMWH). In part C, despite the safety measures implemented, a thromboembolic event occurred in one of seven patients (14%) during the SGN-2FF lead-in period. Of 28 evaluable patients in part A, 1 patient with advanced head and neck squamous cell carcinoma achieved Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 complete response (CR) and 10 (36%) had RECIST v1.1 stable disease, including 1 patient with advanced triple-negative breast cancer with 51% tumor burden reduction. SGN-2FF administration led to dose-proportional increases in exposure and PD reduction in protein fucosylation.

conclusionSGN-2FF demonstrated proof-of-mechanism and preliminary antitumor activity but was associated with thromboembolic events leading to study termination.

Indexed as

Head and Neck NeoplasmsLymphoma, FollicularHeparin, Low-Molecular-WeightHumansMaximum Tolerated DoseResponse Evaluation Criteria in Solid TumorsHeparin, Low-Molecular-WeightClinical trialsFucosylation inhibitorImmunotherapySGN-2FFSmall molecule agents

Identifiers

PMID34288257
PMCPMC8571760
OpenAlexW3183343994

What OpenQuestion holds

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Registered trials

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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.