Evidence map›Paper›PMID 29257710›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2018

Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma.

Kevin D Courtney, Jeffrey R Infante, Elaine T Lam, Robert A Figlin, Brian I Rini, James Brugarolas, Naseem J Zojwalla, Ann M Lowe, Keshi Wang, Eli M Wallace and 2 more

Open access · hybridAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
239citing papers in PubMed, 1 pooled it
12.4field-weighted citation impact, top 1% 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

239 citing papers in PubMed, 1 synthesis or guideline pooled it, 376 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Randomized phase II dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2024
    Trial
  4. Trial
  5. Trial
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. The clinical landscape of HIF2α inhibitors in oncology.Nature reviews. Clinical oncology · 2026
    Review
  12. Article
  13. Article
  14. Review
  15. Overcoming tumour resistance in cancer immunotherapy through predictive and pharmacodynamic biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review

179 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Kevin D CourtneyKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Jeffrey R InfanteKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Elaine T LamKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Robert A FiglinKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Brian I RiniKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
James BrugarolasKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Naseem J ZojwallaKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Ann M LoweKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Keshi WangKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Eli M WallaceKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
John A JoseyKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Toni K ChoueiriKevin D. Courtney and James Brugarolas, University of Texas Southwestern Medical Center; Naseem J. Zojwalla, Ann M. Lowe, Keshi Wang, Eli M. Wallace, and John A. Josey, Peloton Therapeutics, Dallas, TX; Jeffrey R. Infante, TN Oncology and Sarah Cannon Research Institute, Nashville, TN; Elaine T. Lam, University of Colorado Cancer Center, Aurora, CO; Robert A. Figlin, Cedars-Sinai Medical Center, Los Angeles, CA; Brian I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Sarah Cannon · US

Funding

University of Texas Southwestern Medical Center SPORE in Kidney CancerP50CA196516 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Payal Kapur · 2016 to 2026
$24.7M
Paul Calabresis Award in Clinical Oncology ResearchK12CA086913 · NCI · UNIVERSITY OF COLORADO DENVER · PI VIRGINIA F. BORGES, Jill E Slansky · 2000 to 2026
$17.8M
NCI NIH HHS K12 CA086913NCI NIH HHS P50 CA196516
6 · The paper itself

Abstract

Purpose The von Hippel-Lindau tumor suppressor is inactivated in the majority of clear cell renal cell carcinomas (ccRCCs), leading to inappropriate stabilization of hypoxia-inducible factor-2α (HIF-2α). PT2385 is a first-in-class HIF-2α antagonist. Objectives of this first-in-human study were to characterize the safety, pharmacokinetics, pharmacodynamics, and efficacy, and to identify the recommended phase II dose (RP2D) of PT2385. Patients and Methods Eligible patients had locally advanced or metastatic ccRCC that had progressed during one or more prior regimens that included a vascular endothelial growth factor inhibitor. PT2385 was administered orally at twice-per-day doses of 100 to 1,800 mg, according to a 3 + 3 dose-escalation design, followed by an expansion phase at the RP2D. Results The dose-escalation and expansion phases enrolled 26 and 25 patients, respectively. Patients were heavily pretreated, with a median of four (range, one to seven) prior therapies. No dose-limiting toxicity was observed at any dose. On the basis of safety, pharmacokinetic, and pharmacodynamic profiling, the RP2D was defined as 800 mg twice per day. PT2385 was well tolerated, with anemia (grade 1 to 2, 35%; grade 3, 10%), peripheral edema (grade 1 to 2, 37%; grade 3, 2%), and fatigue (grade 1 to 2, 37%; no grade 3 or 4) being the most common treatment-emergent adverse events. No patients discontinued treatment because of adverse events. Complete response, partial response, and stable disease as best response were achieved by 2%, 12%, and 52% of patients, respectively. At data cutoff, eight patients remained in the study, with 13 patients in the study for ≥ 1 year. Conclusion PT2385 has a favorable safety profile and is active in patients with heavily pretreated ccRCC, validating direct HIF-2α antagonism for the treatment of patients with ccRCC.

Indexed as

AdultAgedAged, 80 and overBasic Helix-Loop-Helix ProteinsCarcinoma, Renal CellDose-Response Relationship, DrugEndothelial PAS Domain-Containing Protein 1FemaleHumansIndansKidney NeoplasmsMaleMiddle AgedNeoplasm MetastasisSulfonesBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1IndansPT2385Sulfones

Identifiers

PMID29257710
PMCPMC5946714
OpenAlexW2778771081

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.