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NCT02202759

A Study of MLN0264 in Participants With Cancer of the Stomach or Gastroesophageal Junction

Terminated Phase 2 Results posted Last updated 15 May 2017
What this trial tests

Phase 2 trial testing MLN0264 in Adenocarcinoma of the Stomach in 38 participants. Terminated before completion.

Timeline
4 August 2014
Primary endpoint
15 January 2016
15 January 2016

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment38
Start date4 August 2014
Primary completion15 January 2016
Estimated completion15 January 2016
Sites17 locations across Belgium, United Kingdom, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Adenocarcinoma of the Stomach or Gastroesophageal Junction Expressing Guanylyl Cyclase C. 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.

Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Primary · Day 21, every other cycle, starting with Cycle 2 until disease progression, death or study closure (up to 17 months)

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)0
MLN0264 1.8 mg/kg (GCC Intermediate)14
MLN0264 1.8 mg/kg (GCC High)0
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · From the first dose through 30 days after the last dose of study medication (Up to 10.7 months)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug wil

AEs
GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)8
MLN0264 1.8 mg/kg (GCC Intermediate)15
MLN0264 1.8 mg/kg (GCC High)14
SAEs
GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)2
MLN0264 1.8 mg/kg (GCC Intermediate)5
MLN0264 1.8 mg/kg (GCC High)0
Number of Participants With Potentially Clinically Significant Laboratory Evaluation Findings Secondary · From the first dose through 30 days after the last dose of study medication (Up to 10.7 months)

Participants with at least one post-baseline potentially clinically significant serum chemistry, hematology, coagulation or urinalysis result. Clinically significant results are those that were assessed by the investigator to be Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.

Chemistry
GroupValue95% CI
MLN0264 1.8 mg/kg8
Hematology
GroupValue95% CI
MLN0264 1.8 mg/kg13
Coagulation
GroupValue95% CI
MLN0264 1.8 mg/kg24
Urinalysis
GroupValue95% CI
MLN0264 1.8 mg/kg0
Number of Participants With Potentially Clinically Significant Vital Signs Findings Secondary · Day 1 of each 21 day cycle and 30 days after the last dose of study medication (Up to 10.7 months)

Participants with at least one potentially clinically significant post-baseline vital sign finding including measurements of diastolic and systolic blood pressure, heart rate, and oral temperature.

GroupValue95% CI
MLN0264 1.8 mg/kg0
Progression Free Survival (PFS) Secondary · Time Frame: Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 16.7 months)

PFS is defined as the time in days from the date of first study drug administration to the date of first documentation of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)4038 – 311
MLN0264 1.8 mg/kg (GCC Intermediate)4938 – 316
MLN0264 1.8 mg/kg (GCC High)8739 – 427
Duration of Response Secondary · From first documented response until disease progression (Up to 16.7 months)

Duration of response is defined as the time in days from the date of first documentation of a confirmed response to the date of first documentation of disease progression. Per RECIST v1.1 for target lesions and assessed by magnetic resonance imaging (MRI) - CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

GroupValue95% CI
MLN0264 1.8 mg/kg45.51 – 90
Disease Control Rate Secondary · Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 16.7 months)

Disease control rate is defined as the percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) with a minimum of 12 weeks' duration. CR: Disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the Longest Diameter (LD) of target lesions, taking as reference the baseline sum LD and no new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) of target lesions, taking as reference t

GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)11
MLN0264 1.8 mg/kg (GCC Intermediate)36
MLN0264 1.8 mg/kg (GCC High)54
Overall Survival (OS) Secondary · Until death or 6 months after the last patient completes treatment-whichever occurs first (Up to 17 months)

Overall survival is defined as the time in days from the date of first study drug administration to the date of death.

GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)23079 – 394
MLN0264 1.8 mg/kg (GCC Intermediate)15649 – 505
MLN0264 1.8 mg/kg (GCC High)20624 – 427
MLN0264 Serum Concentrations Secondary · Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.

Blood samples were collected and sent to a laboratory to be tested for serum concentrations of MLN0264.

Cycle 1 Day 1, Pre-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg0.0000± 0.00000
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg37.0434± 9.93577
Cycle 1 Day 1, 4 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg26.0047± 6.27538
Cycle 1 Day 3, 48 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg7.0839± 1.64899
Cycle 1 Day 4, 72 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg4.4939± 1.25657
Cycle 1 Day 8, 168 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg1.6795± 0.71586
Cycle 1 Day 15, 336 Hours Post-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg0.5778± 0.22063
Cycle 2 Day 1, Pre-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg0.7466± 2.68737
Serum Concentration of Total Antibodies (Conjugated and Unconjugated) Secondary · Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.

Blood samples were collected and sent to a laboratory to be tested for conjugated and unconjugated antibodies.

Cycle 1 Day 1, Pre-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg0.0000± 0.00000
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg41.8154± 10.05341
Cycle 1 Day 1, 4 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg35.7626± 8.46954
Cycle 1 Day 3, 48 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg16.0664± 3.26969
Cycle 1 Day 4, 72 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg11.7461± 2.60098
Cycle 1 Day 8, 168 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg6.1851± 1.73972
Cycle 1 Day 15, 336 Hours Post-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg3.3926± 1.00149
Cycle 2 Day 1, Pre-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg2.5995± 3.79916
Serum Concentration of Monomethyl Auristatin E (MMAE) Secondary · Cycles 1-3 pre-dose and 10 minutes, 4 hours, and 3, 4, 8 and 15 days post-dose; Cycles 4-9 and 11-14 pre-dose and 10 minutes post-dose; End of Treatment.

Blood samples were collected and sent to a laboratory to be tested for MMAE.

Cycle 1 Day 1, Pre-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg0.000± 0.0000
Cycle 1 Day 1, 10 Minutes Post-Dose (n=37)
GroupValue95% CI
MLN0264 1.8 mg/kg0.473± 0.6503
Cycle 1 Day 1, 4 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg2.659± 1.5489
Cycle 1 Day 3, 48 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg6.153± 3.2773
Cycle 1 Day 4, 72 Hours Post-Dose (n=35)
GroupValue95% CI
MLN0264 1.8 mg/kg5.856± 3.4519
Cycle 1 Day 8, 168 Hours Post-Dose (n=38)
GroupValue95% CI
MLN0264 1.8 mg/kg2.945± 1.8899
Cycle 1 Day 15, 336 Hours Post-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg0.532± 0.6693
Cycle 2 Day 1, Pre-Dose (n=36)
GroupValue95% CI
MLN0264 1.8 mg/kg0.116± 0.1118
Number of Participants With Reduction From Baseline in Tumor Size Secondary · Day 21 of every other 21-day cycle starting with Cycle 2, 30 days after the last dose of study medication, and then every 12 weeks for up to an additional 6 months (Up to 16.7 months)

The number of participants with the best percentage of tumor reduction from baseline in the sum of the diameter was calculated.

GroupValue95% CI
MLN0264 1.8 mg/kg (GCC Low)138 – 311
MLN0264 1.8 mg/kg (GCC Intermediate)238 – 316
MLN0264 1.8 mg/kg (GCC High)442 – 427

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose through 30 days after the last dose of study drug (up to 10.7 Months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MLN0264 1.8 mg/kg
Serious: 7/38 (18%)
Deaths:

Serious adverse events (9 terms)

ReactionSystemMLN0264 1.8 mg/kg
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Upper gastrointestinal hemorrhageGastrointestinal disorders
Gastric cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour hemorrhageNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AnaemiaBlood and lymphatic system disorders
Supraventricular tachycardiaCardiac disorders
Bile duct obstructionHepatobiliary disorders
Hip fractureInjury, poisoning and procedural complications
Other adverse events (45 terms — click to expand)

ReactionSystemMLN0264 1.8 mg/kg
NauseaGastrointestinal disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
ConstipationGastrointestinal disorders
Oedema peripheralGeneral disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
Blood alkaline phosphatase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Neutrophil count decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Neuropathy peripheralNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
StomatitisGastrointestinal disorders
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
AscitesGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PainGeneral disorders
Urinary tract infectionInfections and infestations
FallInjury, poisoning and procedural complications
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HypoaesthesiaNervous system disorders
TremorNervous system disorders

Most-reported serious reactions: Diarrhoea, Dysphagia, Upper gastrointestinal hemorrhage, Gastric cancer, Tumour hemorrhage, Anaemia, Supraventricular tachycardia, Bile duct obstruction.

Data from ClinicalTrials.gov NCT02202759 adverse events section.

Sponsor's own description

The purpose of this study is to assess the efficacy, safety and tolerability of MLN0264 in patients with recurrent or metastatic guanylyl cyclase C (GCC)-positive adenocarcinoma of the stomach or gastroesophageal junction.

Publications & conference data

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

  1. Stepping forward in antibody-drug conjugate development.
    Jin Y, Schladetsch MA, Huang X, Balunas MJ, et al · · 2022 · cited 136× · PMID 34171334 · DOI 10.1016/j.pharmthera.2021.107917
  2. Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.
    Magee MS, Abraham TS, Baybutt TR, Flickinger JC, et al · · 2018 · cited 117× · PMID 29615399 · DOI 10.1158/2326-6066.cir-16-0362
  3. Current Status of Marine-Derived Compounds as Warheads in Anti-Tumor Drug Candidates.
    Newman DJ, Cragg GM. · · 2017 · cited 43× · PMID 28353637 · DOI 10.3390/md15040099
  4. Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.
    Entezari AA, Snook AE, Waldman SA. · · 2021 · cited 14× · PMID 34056991 · DOI 10.1080/14728222.2021.1937124
  5. GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.
    Lisby AN, Flickinger JC, Bashir B, Weindorfer M, et al · · 2021 · cited 13× · PMID 34027103 · DOI 10.1080/23808993.2021.1876518
  6. Prevalence of antibody drug conjugated-induced nausea and vomiting (ADCINV) in patients with cancer.
    Chow R, Zhang D, Kannout S, Ma A, et al · · 2026 · PMID 42068413 · DOI 10.1007/s00520-026-10674-2

Verify or expand the search:

Other trials of MLN0264

Trials testing the same drug.

Other recruiting trials for Adenocarcinoma of the Stomach

Currently open trials in the same condition.

Other Millennium Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02202759.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing