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NCT03435107

Durvalumab for MSI-H or POLE Mutated Metastatic Colorectal Cancer

Completed Phase 2 Results posted Last updated 15 October 2024
What this trial tests

Phase 2 trial testing Durvalumab in Metastatic Colorectal Cancer in 33 participants. Completed in 26 April 2023.

Timeline
12 April 2018
Primary endpoint
26 April 2023
26 April 2023

Quick facts

Lead sponsorAsan Medical Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment33
Start date12 April 2018
Primary completion26 April 2023
Estimated completion26 April 2023
Sites1 location across South Korea

Drugs / interventions tested

Conditions studied

Sponsor

Asan Medical Center

Who can join

20 and older, any sex, with Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rates (RECIST 1.1) Primary · First measurement should be at 8weeks from first administration.After first measurement, it should be followed up at every 8weeks until date of progression disease or date of death from any cause, whichever came first, assessed up to 46months..

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR): Disappearance of all target lesions Partial Response (PR):\>=30% decrease in the sum of the longest diameter of target lesions Overall Response (OR) = CR + PR

GroupValue95% CI
Durvalumab42.425.5 – 60.8
Disease Control Rate (DCR) Secondary · Through study completion, an average of 2 years and 3months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Disease control rate (DCR); The percentage of patients with the best overall response of complete response (CR), partial response (PR), or stable disease (SD) sustained for at least 6 weeks.

GroupValue95% CI
Durvalumab66.748.2 – 82.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected through study treatment completion, an average of 1 year and 4months. All-Cause Mortality was assessed up to 46months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Durvalumab
Serious: 13/33 (39%)
Deaths: 15/33

Serious adverse events (11 terms)

ReactionSystemDurvalumab
Abdominal painGastrointestinal disorders
Acute Kidney InjuryRenal and urinary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
InfectionInfections and infestations
Both knee painMusculoskeletal and connective tissue disorders
AnorexiaMetabolism and nutrition disorders
Thromboembolic eventVascular disorders
Back painMusculoskeletal and connective tissue disorders
Atypical ductal hyperplasia of breastReproductive system and breast disorders
Anal fistulaSkin and subcutaneous tissue disorders
HyperglycemiaMetabolism and nutrition disorders
Other adverse events (32 terms — click to expand)

ReactionSystemDurvalumab
PruritusSkin and subcutaneous tissue disorders
FatigueGeneral disorders
Abdominal painGastrointestinal disorders
Oral mucositisSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
AnemiaInvestigations
Increased lipaseInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrheaGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations
Alanine aminotransferase increasedInvestigations
Skin rashSkin and subcutaneous tissue disorders
Acute kidney injuryRenal and urinary disorders
Peripheral edemaGeneral disorders
Peripheral neuropathyNervous system disorders
AnorexiaMetabolism and nutrition disorders
Increased amylaseInvestigations
NauseaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DizzinessNervous system disorders
EczemaSkin and subcutaneous tissue disorders
PancreatitisGastrointestinal disorders
HypercholesterolemiaMetabolism and nutrition disorders
HyperthyroidismEndocrine disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
Adrenal insufficiencyEndocrine disorders
Serum sickness-like reactionImmune system disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
ThromboembolismVascular disorders
White blood cell decreasedInvestigations

Most-reported serious reactions: Abdominal pain, Acute Kidney Injury, Dyspnea, Infection, Both knee pain, Anorexia, Thromboembolic event, Back pain.

Data from ClinicalTrials.gov NCT03435107 adverse events section.

Sponsor's own description

The POLE mutations represent high somatic mutation loads in patients with colorectal cancer, especially in those with MMR proficient or MSS, therefore, tumors harbouring POLE mutations might be susceptible to immune checkpoint blockade. Based on these reasons, the investigators planned a phase II study of durvalumab monotherapy in patients with previously treated, metastatic, MMR deficient (MSI-H) or POLE mutated colorectal cancer.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  2. Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy.
    Zhao P, Li L, Jiang X, Li Q. · · 2019 · cited 503× · PMID 31151482 · DOI 10.1186/s13045-019-0738-1
  3. Relationships Between Immune Landscapes, Genetic Subtypes and Responses to Immunotherapy in Colorectal Cancer.
    Picard E, Verschoor CP, Ma GW, Pawelec G. · · 2020 · cited 401× · PMID 32210966 · DOI 10.3389/fimmu.2020.00369
  4. Immunotherapy in colorectal cancer: current achievements and future perspective.
    Fan A, Wang B, Wang X, Nie Y, et al · · 2021 · cited 321× · PMID 34671202 · DOI 10.7150/ijbs.64077
  5. Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside.
    Lizardo DY, Kuang C, Hao S, Yu J, et al · · 2020 · cited 160× · PMID 33035640 · DOI 10.1016/j.bbcan.2020.188447
  6. Predictive biomarkers of colon cancer immunotherapy: Present and future.
    Hou W, Yi C, Zhu H. · · 2022 · cited 100× · PMID 36483562 · DOI 10.3389/fimmu.2022.1032314
  7. Lynch Syndrome and MSI-H Cancers: From Mechanisms to "Off-The-Shelf" Cancer Vaccines.
    Roudko V, Cimen Bozkus C, Greenbaum B, Lucas A, et al · · 2021 · cited 67× · PMID 34630437 · DOI 10.3389/fimmu.2021.757804
  8. Role of DNA repair defects in predicting immunotherapy response.
    Zhang J, Shih DJH, Lin SY. · · 2020 · cited 57× · PMID 32612833 · DOI 10.1186/s40364-020-00202-7

Verify or expand the search:

Other trials of Durvalumab

Trials testing the same drug.

Other recruiting trials for Metastatic Colorectal Cancer

Currently open trials in the same condition.

Other Asan Medical Center trials

Trials by the same sponsor.

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