Evidence map›Paper›PMID 26459177›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016

Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia.

Michael Andreeff, Kevin R Kelly, Karen Yee, Sarit Assouline, Roger Strair, Leslie Popplewell, David Bowen, Giovanni Martinelli, Mark W Drummond, Paresh Vyas and 16 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
224citing papers in PubMed, 1 pooled it
12.2field-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

224 citing papers in PubMed, 1 synthesis or guideline pooled it, 346 citations in OpenAlex.

  1. Pooled it
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  18. Pandora's Box of AML: HowBiomedicines · 2025
    Review
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  20. Article

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

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

26 authors at 5 institutions in 4 countries.

Michael AndreeffThe University of Texas MD Anderson Cancer Center, Houston, Texas. mandreef@mdanderson.org.
Kevin R KellyThe University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Karen YeePrincess Margaret Cancer Centre, Toronto, Ontario, Canada.
Sarit AssoulineMcGill University, Montreal, Quebec, Canada.
Roger StrairCancer Institute of New Jersey/UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Leslie PopplewellCity of Hope National Medical Center, Los Angeles, California.
David BowenSt. James's Institute of Oncology, Leeds, United Kingdom.
Giovanni MartinelliUniversity of Bologna, Bologna, Italy.
Mark W DrummondBeatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
Paresh VyasUniversity of Oxford, Oxford, United Kingdom.
Mark KirschbaumCity of Hope National Medical Center, Los Angeles, California.
Swaminathan Padmanabhan IyerThe University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Vivian RuvoloThe University of Texas MD Anderson Cancer Center, Houston, Texas.
Graciela M Nogueras GonzálezThe University of Texas MD Anderson Cancer Center, Houston, Texas.
Xuelin HuangThe University of Texas MD Anderson Cancer Center, Houston, Texas.
Gong ChenRoche Innovation Center New York, New York.
Bradford GravesFORMA Therapeutics, Boston, Massachusetts.
Steven BlotnerRoche Innovation Center New York, New York.
Peter BridgeRoche Innovation Center New York, New York.
Lori JukofskyRoche Innovation Center New York, New York.
Steve MiddletonRoche Innovation Center New York, New York.
Monica RecknerRoche Innovation Center New York, New York.
Ruediger RuegerRoche Innovative Center Penzberg, Penzberg, Germany.
Jianguo ZhiRoche Innovation Center New York, New York.
Gwen NicholsRoche Innovation Center New York, New York.
Kensuke KojimaThe University of Texas MD Anderson Cancer Center, Houston, Texas.
The University of Texas MD Anderson Cancer Center · USBeatson West of Scotland Cancer Centre · GBMcGill University · CAUniversity of Bologna · ITUniversity of Oxford · GB

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
TOLERANCE INDUCTION BY MEGADOSE STEM CELL TRANSPLANTS IN CML--GVHD AND GVLP01CA049639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI THALL, PETER F · 1990 to 2014
$41.8M
Medical Research Council MC_UU_12009/11NCI NIH HHS CA16672NCI NIH HHS P01 CA049639NCI NIH HHS P01 CA49639NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632
6 · The paper itself

Abstract

purposeRG7112 is a small-molecule MDM2 antagonist. MDM2 is a negative regulator of the tumor suppressor p53 and frequently overexpressed in leukemias. Thus, a phase I study of RG7112 in patients with hematologic malignancies was conducted. EXPERIMENTAL

designPrimary study objectives included determination of the dose and safety profile of RG7112. Secondary objectives included evaluation of pharmacokinetics; pharmacodynamics, such as TP53-mutation status and MDM2 expression; and preliminary clinical activity. Patients were divided into two cohorts: Stratum A [relapsed/refractory acute myeloid leukemia (AML; except acute promyelocytic leukemia), acute lymphoblastic leukemia, and chronic myelogenous leukemia] and Stratum B (relapsed/refractory chronic lymphocytic leukemia/small cell lymphocytic leukemia; CLL/sCLL). Some Stratum A patients were treated at the MTD to assess clinical activity.

resultsRG7112 was administered to 116 patients (96 patients in Stratum A and 20 patients in Stratum B). All patients experienced at least 1 adverse event, and 3 dose-limiting toxicities were reported. Pharmacokinetic analysis indicated that twice-daily dosing enhanced daily exposure. Antileukemia activity was observed in the 30 patients with AML assessed at the MTD, including 5 patients who met International Working Group (IWG) criteria for response. Exploratory analysis revealed TP53 mutations in 14% of Stratum A patients and in 40% of Stratum B patients. Two patients with TP53 mutations exhibited clinical activity. p53 target genes were induced only in TP53 wild-type leukemic cells. Baseline expression levels of MDM2 correlated positively with clinical response.

conclusionsRG7112 demonstrated clinical activity against relapsed/refractory AML and CLL/sCLL. MDM2 inhibition resulted in p53 stabilization and transcriptional activation of p53-target genes. We provide proof-of-concept that MDM2 inhibition restores p53 function and generates clinical responses in hematologic malignancies.

Indexed as

Antineoplastic AgentsApoptosisDNA Mutational AnalysisDrug Administration ScheduleGene ExpressionHumansImidazolinesLeukemia, LymphoidMaximum Tolerated DoseProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53Antineoplastic AgentsImidazolinesMDM2 protein, humanProto-Oncogene Proteins c-mdm2RG7112TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID26459177
PMCPMC4809642
OpenAlexW2182708897

What OpenQuestion holds

Textmetadata
LicenceTDM
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.