Evidence map›Paper›PMID 40145367›Full record

ArticleCancer medicine2025

A Phase I/IB, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab in Combination With Vorinostat in Patients With Advanced Prostate, Renal or Urothelial Carcinoma.

Roberto Pili, David I Quinn, Nabil Adra, Theodore Logan, Sean Colligan, Heather N Burney, Noah M Hahn

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02619253 (A Phase I/Ib, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab), which is not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–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.

NCT02619253 phase1completednot on this map

A Phase I/Ib, Open Label, Dose Finding Study to Evaluate Safety, Pharmacodynamics and Efficacy of Pembrolizumab (MK-3475) in Combination With Vorinostat in Patients With Advanced Renal or Urothelial Cell Carcinoma

TypeinterventionalSponsorNabil AdraRan2016 to 2023Enrolled52ConditionsRenal Cell Carcinoma, Urinary Bladder NeoplasmsArmsPembrolizumab, Vorinostat
3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

7 authors.

Roberto PiliUniversity at Buffalo, Buffalo, New York, USA.ORCID https://orcid.org/0009-0004-9993-9911
David I QuinnUSC Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Nabil AdraIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA.ORCID https://orcid.org/0000-0001-8905-8329
Theodore LoganIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, USA.
Sean ColliganUniversity at Buffalo, Buffalo, New York, USA.
Heather N BurneyIndiana University Department of Biostatistics and Health Data Science, Indianapolis, Indiana, USA.
Noah M HahnThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA.

Funding

Epigenetic modulation of SEC24D and circulating miR-605 in renal cell carcinomaR21CA213977 · NCI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI PILI, ROBERTO · 2017 to 2019
$368k
NCI NIH HHS 1R21 CA213977NCI NIH HHS R21 CA213977
6 · The paper itself

Abstract

backgroundImmunosuppressive factors such as regulatory T cells and myeloid-derived suppressive cells (MDSCs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have immunomodulatory effects. Thus, we conducted a Phase Ib clinical study with the HDAC inhibitor vorinostat and the PD-1 inhibitor pembrolizumab in patients (pts) with metastatic urothelial (UC), renal (RCC) and prostate (PCA) carcinoma.

methodsThe phase I portion consisted of two dose levels of vorinostat (100 and 200 mg, PO daily 2 weeks ON and 1 week OFF) and a fixed dose of pembrolizumab (200 mg IV every 21 days). Patients (pts) were assigned to three cohorts: Cohort A (previously treated, anti-PD1/PD-L1 naïve UC and RCC), Cohort B (previously treated, anti-PD1/PD-L1 resistant UC and RCC pts), and Cohort C (PCA pts).

resultsDose levels 1 and 2 were completed without DLTs. We have enrolled 44 pts. (36 evaluable) in the dose expansion cohorts, and the most common resolved grade 3/4 toxicities were diarrhea, hypophosphatemia, acute kidney injury, anemia, and hypothyroidism. For Cohort A (13 pts), B (11 pts), and C (12 pts) the objective response rate was 8%, 0%, and 17%, and the median progression-free survival was 2.9, 3.5, and 3.5 months, respectively. Four partial responses were observed, and two PCA pts. had a complete biochemical response with undetectable PSA. Persistent lower levels of peripheral CD11

conclusionThe combination of vorinostat and pembrolizumab is relatively well tolerated and may be active in a subset of immune checkpoint-resistant UC/RCC pts. and immune checkpoint-naïve PCA pts.

trial registrationNCT02619253.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsKidney NeoplasmsProstatic NeoplasmsUrologic NeoplasmsVorinostatAdultAgedAged, 80 and overFemaleHistone Deacetylase InhibitorsHumansMaleMiddle AgedAntibodies, Monoclonal, HumanizedHistone Deacetylase InhibitorspembrolizumabVorinostatgenitourinary malignancieshistone deacetylase inhibitorPD‐1 inhibitor

Identifiers

PMID40145367
PMCPMC11947755

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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.