Evidence map›Paper›PMID 20004617›Full record

Trial reportThe Lancet. Oncology2010

Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study.

Jedd D Wolchok, Bart Neyns, Gerald Linette, Sylvie Negrier, Jose Lutzky, Luc Thomas, William Waterfield, Dirk Schadendorf, Michael Smylie, Troy Guthrie and 7 more

Registry-linked trialAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00289640 (A Randomized, Double-Blind, Multi-center, Phase II Fixed Dose Study of Multiple Doses of Ipilimumab), which is not on this map. Cited by 556 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
556citing papers in PubMed, 14 pooled it
25.8field-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.

NCT00289640 phase2completednot on this map

A Randomized, Double-Blind, Multi-center, Phase II Fixed Dose Study of Multiple Doses of Ipilimumab (MDX-010) Monotherapy in Patients With Previously Treated Unresectable Stage III or IV Melanoma

TypeinterventionalSponsorBristol-Myers SquibbRan2006 to 2007Enrolled210ConditionsMelanomaArmsipilimumab (MDX-010, BMS-734016), Ipilimumab
3 · Its place in the literature

Who cites it

556 citing papers in PubMed, 14 syntheses or guidelines pooled it, 1,182 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 13 institutions in 4 countries.

Jedd D WolchokLudwig Center for Cancer Immunotherapy, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. wolchokj@mskcc.org
Bart Neyns
Gerald Linette
Sylvie Negrier
Jose Lutzky
Luc Thomas
William Waterfield
Dirk Schadendorf
Michael Smylie
Troy Guthrie
Jean-Jacques Grob
Jason Chesney
Kevin Chin
Kun Chen
Axel Hoos
Steven J O'Day
Celeste Lebbé
Bristol-Myers Squibb (Germany) · DEAngeles Clinic and Research Institute · USBaptist Cancer Center · USCentre Léon Bérard · FREssen University Hospital · DEHôpital Sainte-Marguerite · FRMemorial Sloan Kettering Cancer Center · USMount Sinai Medical Center · USUniversitair Ziekenhuis Brussel · BEUniversité Claude Bernard Lyon 1 · FRUniversité Paris Cité · FRUniversity of Louisville · USWashington University in St. Louis · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
6 · The paper itself

Abstract

backgroundIpilimumab is a human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 and has shown promising activity in advanced melanoma. We aimed to ascertain the antitumour efficacy of ipilimumab in patients with advanced melanoma.

methodsWe undertook a randomised, double-blind, phase 2 trial in 66 centres from 12 countries. 217 patients with previously treated stage III (unresectable) or stage IV melanoma were randomly assigned a fixed dose of ipilimumab of either 10 mg/kg (n=73), 3 mg/kg (n=72), or 0.3 mg/kg (n=72) every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. Randomisation was done with a permuted block procedure, stratified on the basis of type of previous treatment. The primary endpoint was best overall response rate (the proportion of patients with a complete or partial response, according to modified WHO criteria). Efficacy analyses were done by intention to treat, whereas safety analyses included patients who received at least one dose of ipilimumab. This study is registered with ClinicalTrials.gov, number NCT00289640.

findingsThe best overall response rate was 11.1% (95% CI 4.9-20.7) for 10 mg/kg, 4.2% (0.9-11.7) for 3 mg/kg, and 0% (0.0-4.9) for 0.3 mg/kg (p=0.0015; trend test). Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0.3 mg/kg, respectively; the most common grade 3-4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0.3 mg/kg group) and diarrhoea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0.3 mg/kg group).

interpretationIpilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg.

fundingBristol-Myers Squibb.

Indexed as

AdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic AgentsDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansIpilimumabMaleMelanomaMiddle AgedSkin NeoplasmsAntibodies, MonoclonalAntineoplastic AgentsIpilimumab

Identifiers

PMID20004617
OpenAlexW2095826876

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.