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NCT04479436

A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer

Terminated Phase 2 Results posted Last updated 18 May 2025
What this trial tests

Phase 2 trial testing Patritumab Deruxtecan in Metastatic Colorectal Cancer in 40 participants. Terminated before completion.

Timeline
14 September 2020
Primary endpoint
3 February 2022
3 February 2022

Quick facts

Lead sponsorDaiichi Sankyo
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment40
Start date14 September 2020
Primary completion3 February 2022
Estimated completion3 February 2022
Sites46 locations across France, Italy, Japan, Belgium, United Kingdom, Poland, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo — full company profile →

Who can join

Adults 18 to 100, 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 Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Primary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2
Cohort 2: HER3 Low/Negative (IHC 1+, 0)0
Duration of Response (DoR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

DoR defined as the time from the first documented response (CR or PR) to the date of disease progression or death due to any cause. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

Duration of Response: BICR
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2.912.79 – 3.02
Duration of Response: Investigator
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)4.482.56 – 6.41
Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

ORR defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesion based on RECIST v1.1.

GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2
Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

DCR is defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review or by the Investigator. Based on RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of

Disease control rate (BICR)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)22
Disease control rate (Investigator)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)22
Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

TTR defined as the time from the start of study treatment to the date of the first documentation of objective response (complete response \[CR\] or partial response \[PR\]) that is subsequently confirmed by Blinded Independent Central Review or by the Investigator. CR was defined as a disappearance of all lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

Time to tumor response (BICR)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)1.99± 0.813
Time to tumor response (Investigator)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)1.53± 0.163
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD or death due to any cause, whichever is earlier.

Progression-free survival (BICR)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2.271.51 – 2.96
Cohort 2: HER3 Low/Negative (IHC 1+, 0)5.5
Progression-free survival (Investigator)
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2.531.64 – 3.71
Overall Survival (OS) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

OS defined as the time from the start of study treatment to the date of death due to any cause.

GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)10.585.36 – 12.09
Cohort 2: HER3 Low/Negative (IHC 1+, 0)8.9
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Other Safety Parameters During the Study Secondary · From Baseline (Day 0) to data cut off (up to approximately 16.5 months)

TEAEs, study-drug related TEAE, serious adverse events (SAE), study-drug related SAE, and adverse events of special interest (eg. interstitial lung disease and elevation of aminotransferases and total bilirubin) were assessed. A TEAE was defined as an AE with a start or worsening date during the on-treatment period. An SAE was an AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.

Treatment-emergent adverse events (TEAEs)
GroupValue95% CI
Overall40
Study-drug related TEAE
GroupValue95% CI
Overall37
Serious TEAE (SAE)
GroupValue95% CI
Overall17
Study-drug related SAE
GroupValue95% CI
Overall9
Adverse event of special interest (AESI)
GroupValue95% CI
Overall2
Number of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) Secondary · At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).

Blood samples were collected to assess the immunogenicity of U3-1402.

Baseline: Positive
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
Baseline: Negative
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)37
Baseline: Missing
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)2
Post-baseline: Positive
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
Post-baseline: Negative
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)38
Number of Participants Who Have Treatment-emergent Anti-Drug Antibody (ADA) Secondary · At Baseline, and post-Baseline. Post-Baseline including any of the following timepoints- Cycle 1, Days 1&8; Cycles 2&4 and every 2 cycles thereafter, Day 1 (each cycle, 21 days), and at EOT (~16.5 months).

Blood samples were collected to assess the immunogenicity of U3-1402. Treatment-emergent ADA was defined as participants with a negative ADA status at Baseline who had a positive ADA status post-Baseline (treatment-induced ADA), or participants with a positive ADA status at both Baseline and post-Baseline but with an increase of at least 4-fold in ADA titer from Baseline to post-Baseline (treatment-boosted ADA), or participants who had missing ADA data at Baseline and had a positive ADA status post-Baseline.

Treatment-emergent ADA
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
Treatment-induced ADA
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
Treatment-boosted ADA
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
ADA missing at baseline but positive at post-baseline
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)0
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Serum PK parameter Cmax (antibody drug conjugate \[ADC\], total anti-HER3 antibody, and MAAA-1181a) were assessed in the full PK sampling cohort using noncompartmental methods.

U3-1402: Cycle 1
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)155.67± 43.45
U3-1402: Cycle 3
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)159.80± 47.94
Total anti-HER3 antibody: Cycle 1
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)154.08± 32.82
Total anti-HER3 antibody: Cycle 3
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)153.86± 39.31
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) of MAAA-1181a Following Administration of U3-1402 In Participants With Advanced or Metastatic Colorectal Cancer Secondary · At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 and Cycle 3 (each cycle is 21 days)

Serum PK parameter Cmax of MAAA-1181a was assessed in the full PK sampling cohort using noncompartmental methods.

Cycle 1
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)38.09± 19.68
Cycle 3
GroupValue95% CI
Cohort 1: HER3 High (IHC 3+, 2+)16.13± 9.29

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were collected for approximately 16.5 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Overall
Serious: 17/40 (43%)
Deaths: 23/40

Serious adverse events (26 terms)

ReactionSystemOverall
Disease progressionGeneral disorders
Abdominal painGastrointestinal disorders
Acute kidney injuryRenal and urinary disorders
Febrile neutropeniaBlood and lymphatic system disorders
NauseaGeneral disorders
Acute respiratory failureRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Biliary obstructionHepatobiliary disorders
Cauda equina syndromeNervous system disorders
Cytomegalovirus infectionInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
HyperbilirubinaemiaHepatobiliary disorders
HypokalaemiaMetabolism and nutrition disorders
International normalised ratio increasedInvestigations
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Liver abscessInfections and infestations
Platelet count decreasedInvestigations
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
PyelonephritisInfections and infestations
Rectal haemorrhageGastrointestinal disorders
Rectal obstructionGastrointestinal disorders
SepsisInfections and infestations
Small intestinal obstructionGastrointestinal disorders
Other adverse events (48 terms — click to expand)

ReactionSystemOverall
FatigueGeneral disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
Platelet count decreasedInvestigations
ConstipationGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
Lymphocyte count decreasedInvestigations
RashSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
White blood cell count decreasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
StomatitisGastrointestinal disorders
DizzinessNervous system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
PyrexiaGeneral disorders
HyperbilirubinaemiaHepatobiliary disorders
HeadacheNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
Disease progressionGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
HypertensionVascular disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Blood lactate dehydrogenase increasedInvestigations
Weight decreasedInvestigations
DehydrationMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Disease progression, Abdominal pain, Acute kidney injury, Febrile neutropenia, Nausea, Acute respiratory failure, Anaemia, Biliary obstruction.

Data from ClinicalTrials.gov NCT04479436 adverse events section.

Sponsor's own description

This study is designed to primarily evaluate the safety and efficacy of U3-1402 in participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2 prior lines of therapy and will explore clinical benefit according to human epidermal growth factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.

Publications & conference data

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

  1. Antibody-Drug Conjugates for Cancer Therapy.
    Hafeez U, Parakh S, Gan HK, Scott AM. · · 2020 · cited 283× · PMID 33081383 · DOI 10.3390/molecules25204764
  2. Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, <i>EGFR</i>-Mutated Non-Small Cell Lung Cancer.
    Jänne PA, Baik C, Su WC, Johnson ML, et al · · 2022 · cited 236× · PMID 34548309 · DOI 10.1158/2159-8290.cd-21-0715
  3. Antibody-drug conjugates in solid tumors: a look into novel targets.
    Criscitiello C, Morganti S, Curigliano G. · · 2021 · cited 169× · PMID 33509252 · DOI 10.1186/s13045-021-01035-z
  4. Payload diversification: a key step in the development of antibody-drug conjugates.
    Conilh L, Sadilkova L, Viricel W, Dumontet C. · · 2023 · cited 152× · PMID 36650546 · DOI 10.1186/s13045-022-01397-y
  5. Targeting cancer with antibody-drug conjugates: Promises and challenges.
    Dean AQ, Luo S, Twomey JD, Zhang B. · · 2021 · cited 145× · PMID 34291723 · DOI 10.1080/19420862.2021.1951427
  6. Thirty Years of HER3: From Basic Biology to Therapeutic Interventions.
    Haikala HM, Jänne PA. · · 2021 · cited 84× · PMID 33608318 · DOI 10.1158/1078-0432.ccr-20-4465
  7. HER3 in cancer: from the bench to the bedside.
    Gandullo-Sánchez L, Ocaña A, Pandiella A. · · 2022 · cited 71× · PMID 36271429 · DOI 10.1186/s13046-022-02515-x
  8. EGFR Inhibition Enhances the Cellular Uptake and Antitumor-Activity of the HER3 Antibody-Drug Conjugate HER3-DXd.
    Haikala HM, Lopez T, Köhler J, Eser PO, et al · · 2022 · cited 61× · PMID 34548332 · DOI 10.1158/0008-5472.can-21-2426

Verify or expand the search:

Other trials of Patritumab Deruxtecan

Trials testing the same drug.

Other recruiting trials for Metastatic Colorectal Cancer

Currently open trials in the same condition.

Other Daiichi Sankyo trials

Trials by the same sponsor.

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