Evidence map›Paper›PMID 31118108›Full record

ArticleJournal for immunotherapy of cancer2019

Safety and enhanced immunostimulatory activity of the DRD2 antagonist ONC201 in advanced solid tumor patients with weekly oral administration.

Mark N Stein, Jyoti Malhotra, Rohinton S Tarapore, Usha Malhotra, Ann W Silk, Nancy Chan, Lorna Rodriguez, Joseph Aisner, Robert D Aiken, Tina Mayer and 24 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
4.0field-weighted citation impact, top 5% 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.

NCT02250781 phase1completednot on this map

A First-in-Human Phase I Single-Agent Open-Label Dose-Escalation Study of Every Three-Week Dosing of Oral ONC201 in Patients With Advanced Solid Tumors

TypeinterventionalSponsorRutgers, The State University of New JerseyRan2015 to 2018Enrolled58ConditionsSolid TumorsArmsOral ONC201
NCT02324621 phase1completednot on this map

A Continuation Clinical Trial of Every Three-Week Dosing of Oral ONC201 in Patients With Advanced Solid Tumors

TypeinterventionalSponsorRutgers, The State University of New JerseyRan2015 to 2018Enrolled26ConditionsUnspecified Adult Solid TumorArmsOral ONC201, pharmacological study, laboratory biomarker analysis
3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Phase II Study of ONC201 in Neuroendocrine Tumors including Pheochromocytoma-Paraganglioma and Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Trial
  4. Trial
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Case Report: Application ofFrontiers in oncology · 2025
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. ONC201 (Dordaviprone) in Recurrent H3 K27M-Mutant Diffuse Midline Glioma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    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

34 authors at 3 institutions in 1 country.

Mark N SteinDivision of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA.
Jyoti MalhotraRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Rohinton S TaraporeOncoceutics, Inc, Philadelphia, PA, USA.
Usha MalhotraRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Ann W SilkRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Nancy ChanRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Lorna RodriguezRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Joseph AisnerRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Robert D AikenRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Tina MayerRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Bruce G HafftyRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Jenna H NewmanRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Salvatore M AspromonteRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Praveen K BommareddyRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Ricardo EstupinianRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Charles B ChessonRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Evita T SadiminRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Shengguo LiRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Daniel J MedinaRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Tracie SaundersRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Melissa FrankelRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Aparna KareddulaRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Sherrie DamareRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Elayne WesolowskyRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Christian GabelRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Wafik S El-DeiryWarren Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Varun V PrabhuOncoceutics, Inc, Philadelphia, PA, USA.
Joshua E AllenOncoceutics, Inc, Philadelphia, PA, USA.
Martin StogniewOncoceutics, Inc, Philadelphia, PA, USA.
Wolfgang OsterOncoceutics, Inc, Philadelphia, PA, USA.
Joseph R BertinoRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Steven K LibuttiRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
Janice M MehnertRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. mehnerja@cinj.rutgers.edu.
Andrew ZlozaRutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. andrew_zloza@rush.edu.ORCID 0000-0001-8844-6493
Rutgers, The State University of New Jersey · USOncoceutics (United States) · USJohn Brown University · US

Funding

TRANSCRIPTIONAL PROFILINGP30CA072720 · NCI · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI Shridar Ganesan · 1997 to 2026
$94.5M
TIC10 anti-tumor effect through regulation of Foxo3a and TRAILR01CA173453 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI EL-DEIRY, WAFIK S. · 2013 to 2023
$4.3M
NCI NIH HHS P30 CA072720NCI NIH HHS R01 CA173453
6 · The paper itself

Abstract

backgroundONC201 is a small molecule antagonist of DRD2, a G protein-coupled receptor overexpressed in several malignancies, that has prolonged antitumor efficacy and immunomodulatory properties in preclinical models. The first-in-human trial of ONC201 previously established a recommended phase II dose (RP2D) of 625 mg once every three weeks. Here, we report the results of a phase I study that evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of weekly ONC201.

methodsPatients ≥ 18 years old with an advanced solid tumor refractory to standard treatment were enrolled. Dose escalation proceeded with a 3 + 3 design from 375 mg to 625 mg of ONC201. One cycle, also the dose-limiting toxicity (DLT) window, was 21 days. The primary endpoint was to determine the RP2D of weekly ONC201, which was confirmed in an 11-patient dose expansion cohort.

resultsTwenty patients were enrolled: three at 375 mg and 17 at 625 mg of ONC201. The RP2D was defined as 625 mg with no DLT, treatment discontinuation, or dose modifications due to drug-related toxicity. PK profiles were consistent with every-three-week dosing and similar between the first and fourth dose. Serum prolactin and caspase-cleaved cytokeratin-18 induction were detected, along with intratumoral integrated stress response activation and infiltration of granzyme B+ Natural Killer cells. Induction of immune cytokines and effectors was higher in patients who received ONC201 once weekly versus once every three weeks. Stable disease of > 6 months was observed in several prostate and endometrial cancer patients.

conclusionsWeekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation.

trial registrationNCT02250781 (Oral ONC201 in Treating Patients With Advanced Solid Tumors), NCT02324621 (Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors).

Indexed as

Administration, OralAdultAgedAged, 80 and overAntineoplastic AgentsHumansMiddle AgedNeoplasmsReceptors, Dopamine D2Antineoplastic AgentsDRD2 protein, humanReceptors, Dopamine D2CancerDopamineImmuno-oncologyImmunotherapyONC201Solid tumors

Identifiers

PMID31118108
PMCPMC6532211
OpenAlexW2947518394

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.