Evidence map›Paper›PMID 41041866›Full record

ArticleMolecular cancer therapeutics2026

Preclinical Activity of the DLL3-Targeted T-cell Engager MK-6070 in Neuroendocrine Prostate Cancer.

Sheng-Yu Ku, Nishat Manzar, Maria Mica Garcia, Min Jin Kim, David J Einstein, Steven P Balk, Yasutaka Yamada, Himisha Beltran

Registry-linked trialAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04471727 (A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 Monotherapy and HPN328 With Atezolizumab or Ifinatamab Deruxtecan), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

NCT04471727 phase1 / phase2active not recruitingnot on this map

A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 Monotherapy and HPN328 With Atezolizumab or Ifinatamab Deruxtecan (I-DXd) in Patients With Advanced Cancers Associated With Expression of Delta-like Canonical Notch Ligand 3 (DLL3).

TypeinterventionalSponsorHarpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Ran2020 to 2028Enrolled232ConditionsSmall-Cell Lung Cancer, Neuroendocrine CarcinomaArmsGocatamig, Atezolizumab, Ifinatamab Deruxtecan (I-DXd)
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
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

8 authors.

Sheng-Yu KuDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-4715-1888
Nishat ManzarDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-3628-6832
Maria Mica GarciaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0009-5194-9252
Min Jin KimDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0009-0009-5330-3439
David J EinsteinHematology and Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9163-3281
Steven P BalkHematology and Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4546-7371
Yasutaka YamadaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0002-0070-1590
Himisha BeltranDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.ORCID 0000-0003-3259-2226

Funding

Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI KANTOFF, PHILIP W · 2002 to 2017
$36.2M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
Molecular Determinants of Response and Resistance to EZH2 and PARP inhibition in Prostate CancerP50CA272390 · NCI · DANA-FARBER CANCER INST · PI Steven P. Balk, Himisha Beltran · 2023 to 2026
$12.0M
Molecular mechanisms underlying lineage plasticity in prostate cancerR37CA241486 · NCI · DANA-FARBER CANCER INST · PI Himisha Beltran · 2020 to 2026
$4.1M
"DNMT and TET1 reprogramming as a targetable mechanism of resistance in advanced prostate cancer"R01CA274963 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI Himisha Beltran, David S. Rickman · 2023 to 2026
$2.6M
National Cancer Institute (NCI) P50 CA272390-01National Cancer Institute (NCI) R37CA241486-01A1National Cancer Institute (NCI) RO1CA274963NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA090381NCI NIH HHS P50 CA272390NCI NIH HHS R01 CA274963NCI NIH HHS R37 CA241486Prostate Cancer Foundation (PCF)U.S. Department of Defense (DOD) HT94252310407
6 · The paper itself

Abstract

Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer with limited therapeutic options. Delta-like ligand 3 (DLL3) is a cell-surface protein and therapeutic target expressed in the vast majority of NEPC tumors. The DLL3-targeted T cell-activating construct MK-6070 (formerly called HPN328) binds to both DLL3 on tumor cells and CD3 on T cells, as well as serum albumin to extend half-life. A phase I/II trial of MK-6070 is currently underway, which includes an NEPC cohort (NCT04471727). In this study, we report the preclinical activity of MK-6070 in prostate cancer models, showing high specificity and antitumor activity in DLL3-expressing NEPC models both in vitro and in vivo, with T-cell activation and tumor infiltration of T cells after treatment. MK-6070 also demonstrates antitumor activity in mixed tumors, affecting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate the promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070.

Indexed as

Intracellular Signaling Peptides and ProteinsMembrane ProteinsNeuroendocrine TumorsProstatic NeoplasmsT-LymphocytesAnimalsCell Line, TumorHumansMaleMiceXenograft Model Antitumor AssaysDLL3 protein, humanIntracellular Signaling Peptides and ProteinsMembrane Proteins

Identifiers

PMID41041866
PMCPMC12554248

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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.