Evidence map›Paper›PMID 40042547›Full record

ArticleInvestigational new drugs2025

First-in-human, phase 1 dose escalation study of SL-279252, a hexameric PD1-Fc-OX40L fusion protein, in patients with advanced solid tumors and lymphoma.

Melissa Johnson, David Hong, Irene Braña, Patrick Schöffski, Vladimir Galvao, Fatima Rangwala, Bo Ma, Robert Hernandez, Asha Kamat, Kazunobu Kato and 3 more

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Publisher
In one paragraph

Article in Investigational new drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03894618 (Phase 1 Dose Escalation and Dose Expansion Study of an Agonist Redirected Checkpoint Fusion Protein, SL-279252), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

NCT03894618 phase1completednot on this map

Phase 1 Dose Escalation and Dose Expansion Study of an Agonist Redirected Checkpoint Fusion Protein, SL-279252 (PD1-Fc-OX40L), in Subjects With Advanced Solid Tumors or Lymphomas

TypeinterventionalSponsorShattuck Labs, Inc.Ran2019 to 2023Enrolled49ConditionsSquamous Cell Carcinoma of the Head and Neck, Melanoma, Non Small Cell Lung Cancer, Urothelial CarcinomaArmsSL-279252
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

13 authors.

Melissa JohnsonSarah Cannon Research Institute, Nashville, TN, USA.
David HongMD Anderson Cancer Center, Houston, TX, USA.
Irene BrañaVall d'Hebron Institute of Oncology, Barcelona, Spain.
Patrick SchöffskiUniversity Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
Vladimir GalvaoVall d'Hebron Institute of Oncology, Barcelona, Spain.
Fatima RangwalaShattuck Labs, Durham, NC, 27709, USA.
Bo MaShattuck Labs, Durham, NC, 27709, USA.
Robert HernandezShattuck Labs, Durham, NC, 27709, USA.
Asha KamatShattuck Labs, Durham, NC, 27709, USA.
Kazunobu KatoShattuck Labs, Durham, NC, 27709, USA.
Taylor H SchreiberShattuck Labs, Durham, NC, 27709, USA.
Lini PanditeShattuck Labs, Durham, NC, 27709, USA. lpandite@shattucklabs.com.
Lillian L SiuPrincess Margaret Cancer Center, Toronto, Canada.

Funding

Shattuck Labs NA
6 · The paper itself

Abstract

SL-279252 is a bifunctional hexameric fusion protein adjoining the extracellular domains of PD-1 and OX40L via an inert IgG4 derived Fc domain. A Phase 1 dose escalation study was conducted in patients (pts) with advanced solid tumors or lymphomas. SL-279252 was administered intravenously across 12 dose levels (range: 0.0001-24 mg/kg). Objectives included evaluation of safety, dose-limiting toxicity (DLT), recommended phase 2 dose, pharmacokinetic and pharmacodynamic (PD) parameters, and anti-tumor activity. Forty-nine pts (48 with solid tumor and 1 with lymphoma) were enrolled (median age 64 years; 53% male; median [range] of 3 [0-5] prior systemic therapies; 61% had been previously treated with PD-1/L1 inhibitors). Most common treatment-related adverse events (AEs) were infusion-related reaction (16%), maculopapular rash (10%), fatigue (6%), and neutropenia (6%). Treatment-related Grade (G) 3 AE was neutropenia (4%). There were no G4 or G5 AEs or DLTs. SL-279252 Cmax and area under the curve (AUC) increased proportionally with dose. T½ was ~ 20 h. Baseline anti-drug antibodies (ADA) were observed in 11/42 pts who had received a PD-1 inhibitor within 250 days. 7/31 pts had a persistent SL-279252 induced ADA response. PD effects consistent with OX40 engagement included dose dependent egress of CD4 + OX40 + cells and increases in Ki67 + CD4 and CD8 central and effector memory cells in the blood. Best response by iRECIST [1] in 46 response evaluable subjects was 1 iPR and 15 iSD. SL-279252 was well tolerated. PD effects consistent with OX40 activation were observed, however, efficacy was limited which may have been due to the disease characteristics, prior treatment with PD-1/L1 inhibitors, neutralization of the PD-1 domain of SL-279252 by circulating PD-1 inhibitors, limited SL-279252 penetration into tumors or other variables. Trial register number NCT03894618. Trial registration date 28-March-2019.

Indexed as

Antineoplastic AgentsLymphomaNeoplasmsProgrammed Cell Death 1 ReceptorRecombinant Fusion ProteinsAdultAgedAged, 80 and overDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedAntineoplastic AgentsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorRecombinant Fusion ProteinsImmunotherapyOX40LPD-1PD1-Fc-OX40LPharmacodynamicsPharmacokineticsSafety

Identifiers

PMID40042547

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.