Evidence map›Paper›PMID 36007963›Full record

Trial reportJournal for immunotherapy of cancer2022

Phase II study of durvalumab (anti-PD-L1) and trametinib (MEKi) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

Benny Johnson, Cara L Haymaker, Edwin R Parra, Luisa Maren Solis Soto, Xuemei Wang, Jane V Thomas, Arvind Dasari, Van K Morris, Kanwal Raghav, Eduardo Vilar and 13 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03428126 (Phase II Study of Durvalumab), which is not on this map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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.

NCT03428126 phase2completednot on this map

Phase II Study of Durvalumab (MEDI4736) (Anti-PD-L1) and Trametinib (MEKi) in MSS Metastatic Colon Cancer

TypeinterventionalSponsorM.D. Anderson Cancer CenterRan2018 to 2022Enrolled29ConditionsMalignant Neoplasms of Digestive Organs, Colorectal Cancer, Colon CancerArmsDurvalumab, Trametinib
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Review
  6. Review
  7. Review
  8. Metabolic stress conditions dictate MAPKAPK2-dependent efficiency of MEK1/2 inhibition in colorectal carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review
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

23 authors at 2 institutions in 1 country.

Benny JohnsonDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA BJohnson6@mdanderson.org.ORCID 0000-0003-3683-8115
Cara L HaymakerDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Edwin R ParraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Luisa Maren Solis SotoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xuemei WangDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jane V ThomasDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Arvind DasariDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Van K MorrisDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Kanwal RaghavDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Eduardo VilarDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.ORCID 0000-0001-6404-3761
Bryan K KeeDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cathy EngDepartment of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Christine M ParseghianDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Robert A WolffDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Younghee LeeDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Daniele LorenziniDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Caddie Laberiano-FernandezDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Anuj VermaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Wenhua LangDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ignacio I WistubaDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Andrew FutrealDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Scott KopetzDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Michael J OvermanDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The University of Texas MD Anderson Cancer Center · USVanderbilt University · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Translational Cancer Immune Monitoring and Analysis Center (TCIMAC)U24CA224285 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gheath Al-Atrash, Cara L Haymaker · 2017 to 2026
$16.7M
Project 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT · 2019 to 2023
$11.0M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221707NCI NIH HHS U24 CA224285
6 · The paper itself

Abstract

backgroundMonotherapy with immune checkpoint blockade is ineffective for patients (pts) with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). This study investigates whether the combination of trametinib (T) with durvalumab (D) can alter the immune tumor microenvironment (TME) by successfully priming and activating T-cells.

methodsOpen-label, single-center, phase II trial with primary endpoint of immune-related response rate for combination of T+D in refractory MSS mCRC pts (NCT03428126). T is 2 mg/day orally starting 1 week prior to D, which is given 1500 mg intravenously every 4 weeks. Simon 2-stage design used to enroll 29 pts into first stage, requiring a response in two or more pts to proceed to stage 2. Tumor biopsies were collected at baseline (BL) and early on-treatment (OT) at week 4.

resultsTwenty nine treated pts include 48% females, median age 48 years (range 28-75), and median prior therapies 2 (range 1-5). No grade (G) 4 or 5 treatment-related adverse events (TRAE). The most common TRAE of any grade was acneiform rash, 17% being G3. One of 29 pts had confirmed partial response (PR) lasting 9.3 months (mo) for an overall response rate of 3.4%. Seven pts had stable disease (SD) and five pts (1 PR, 4 SD) demonstrated decrease in total carcinoembryonic antigen ng/mL (best percentage reduction: 94%, 95%, 42%, 34%, and 22%, respectively). Median progression-free survival was 3.2 mo (range 1.1-9.3 months). Three pts with both liver and lung metastases demonstrated discrepant responses in which clinical benefit was present in the lung metastases but not liver metastases. Comparison of BL and 4-week OT tumor tissue flow cytometry demonstrated no changes in T-cell infiltration but upregulation expression of PD-1 and Tim3 on CD8 T cells. However, expression of PD-1 and Tim3 as single markers and as coexpressed markers was observed to increase OT relative to BL (p=0.03, p=0.06 and p=0.06, respectively).

conclusionsT+D demonstrated acceptable tolerability in pts with refractory MSS mCRC. The response rate in the first stage of the study did not meet efficacy criteria to proceed to the second stage. Specific site of metastatic disease may impact outcomes in novel immunotherapy combination trials. TRIAL REGISTRATION NUMBER: NCT03428126.

Indexed as

Colorectal NeoplasmsLung NeoplasmsAdultAgedAntibodies, MonoclonalFemaleHepatitis A Virus Cellular Receptor 2HumansMaleMicrosatellite RepeatsMiddle AgedProgrammed Cell Death 1 ReceptorPyridonesPyrimidinonesTumor MicroenvironmentAntibodies, MonoclonaldurvalumabHepatitis A Virus Cellular Receptor 2Programmed Cell Death 1 ReceptorPyridonesPyrimidinonestrametinibClinical Trials, Phase II as TopicImmunotherapy

Identifiers

PMID36007963
PMCPMC9422817
OpenAlexW4293239387

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.