The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Other or Multiple Cancer Types

Disitamab vedotin

Disitamab vedotin is an investigational compound. Its safety and efficacy have not been established.

A Phase 1b/2 Open-Label Study of Disitamab Vedotin Monotherapy or in Combination With Other Anticancer Therapies in Solid Tumors
Phase 1 /2
NCT06157892

Active enrolling

Globe
Locations

United States, Australia, Canada, Italy, Spain

Study design

Participant Group/Arm

EXPERIMENTAL: Dose Escalation - Previously treated advanced GC/GEJC or breast cancer

disitamab vedotin + tucatinib

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)

DRUG: tucatinib

300mg given twice daily by mouth (orally)
Participant Group/Arm

EXPERIMENTAL: Cohort A monotherapy - HER2-low 2L or 3L breast cancer

disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)
Participant Group/Arm

EXPERIMENTAL: Cohort A - HER2-low 2L or 3L breast cancer

disitamab vedotin + tucatinib

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)

DRUG: tucatinib

300mg given twice daily by mouth (orally)
Participant Group/Arm

EXPERIMENTAL: Cohort B monotherapy - HER2+ 3L or higher breast cancer

disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)
Participant Group/Arm

EXPERIMENTAL: Cohort B - HER2+ 3L or higher breast cancer

disitamab vedotin + tucatinib

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)

DRUG: tucatinib

300mg given twice daily by mouth (orally)
Participant Group/Arm

EXPERIMENTAL: Cohort C monotherapy - HER2-low 2L GC/GEJC

disitamab vedotin monotherapy

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)
Participant Group/Arm

EXPERIMENTAL: Cohort C - HER2-low 2L GC/GEJC

disitamab vedotin + tucatinib

Intervention/Treatment

DRUG: disitamab vedotin

Given into the vein (IV; intravenous)

DRUG: tucatinib

300mg given twice daily by mouth (orally)
Study design table for Clinical Trial

Key eligibility criteria

Inclusion criteria
General Inclusion Criteria
  • Measurable disease according to RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Dose Escalation Phase Inclusion Criteria
  • Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
  • Locally-advanced, unresectable, or metastatic stage
  • HER2 status IHC 1+ or higher by most recent local assessment.
  • Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies. Cohort A (HER2-Low Breast Cancer) Inclusion Criteria
  • Histologically or cytologically confirmed diagnosis of breast carcinoma
  • Locally-advanced, unresectable, or metastatic stage
  • HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH-negative)
  • Prior therapies requirements
    • No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC.
    • Participants with known BRCA mutation must have received a PARP-inhibitor where available and not medically contraindicated
    • Have progression on or after, or intolerant to, T-DXd, sacituzumab govitecan, or other topoisomerase I inhibitor therapies, if available as local standard of care therapy
    • Participants with HR+ tumors must have endocrine therapy refractory disease:
  • Prior therapies requirements
    • Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab with chemotherapy if available as local standard of care therapy.
  • Histologically or cytologically confirmed diagnosis breast carcinoma
  • Locally-advanced, unresectable, or metastatic stage
  • HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
  • Participants must have:
    • Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy.
    • Have progression on or after, or intolerant to, T-DXd or other topoisomerase I inhibitor therapies
    • No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC
  • Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
  • Locally-advanced, unresectable, or metastatic stage
  • HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment
  • Willing and able to provide archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks
  • Participants must have received:
    • Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease
    • Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC
    • Prior anti-PD-(L)1 therapy is allowed
    • No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GE
  • Must not have received prior treatment with HER2 directed therapy
Exclusion criteria
  • Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
  • Prior therapy with ADCs with MMAE payload
  • Prior therapy with tucatinib
  • Active CNS and/or leptomeningeal metastasis.
  • Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks prior to first dose of study treatment
  • History of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
  • Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications
  • Key dates

    Study start date
    • May 2024
    Estimated primary completion date
    • January 2030

    Key endpoints

    Primary Outcome Measures
    Outcome Measure

    Number of participants with dose limiting toxicities DLTs) in dose escalation phase

    Measure Description

    Time Frame

    Up to 28 days

    Outcome Measure

    Number of participants with adverse events (AEs)

    Measure Description

    Any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention

    Time Frame

    Through 30 days after the last study treatment; approximately 5 years

    Outcome Measure

    Number of participants with laboratory abnormalities

    Measure Description

    Time Frame

    Through 30-37 days after the last study treatment: approximately 5 years

    Outcome Measure

    Number of participants with dose alterations

    Measure Description

    Time Frame

    Through 30-37 days after the last study treatment: approximately 5 years

    Outcome Measure

    Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment

    Measure Description

    The proportion of participants with confirmed response (CR) or partial response (PR) according to RECIST v1.1.

    Time Frame

    Approximately 3 years

    Primary Outcome Measures table for Clinical Trial
    Secondary Outcome Measures:
    Outcome Measure

    Duration of response (DOR) per RECIST v1.1 by investigator assessment

    Measure Description

    The time from start of the first documentation of objective tumor response of CR or PR (that is subsequently confirmed) to the first documentation of progressive disease (PD) per RECIST v1.1, or to death due to any cause

    Time Frame

    Approximately 5 years

    Outcome Measure

    Disease control rate (DCR) per RECIST v1.1 by investigator assessment

    Measure Description

    The proportion of participants with stable disease (SD) or confirmed CR or PR according to RECIST v1.1.

    Time Frame

    Approximately 5 years

    Outcome Measure

    Progression free survival (PFS) per RECIST v1.1 by investigator assessment

    Measure Description

    The time from randomization (or Cycle 1 Day 1 for participants in dose escalation phase) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

    Time Frame

    Approximately 5 years

    Outcome Measure

    Overall survival (OS)

    Measure Description

    The time from randomization (or Cycle 1 Day 1 for participants in dose escalation phase) to the date of death due to any cause.

    Time Frame

    Approximately 5 years

    Outcome Measure

    Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)

    Measure Description

    Time Frame

    Through 30-37 days after the last study treatment; approximately 5 years

    Outcome Measure

    PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)

    Measure Description

    Time Frame

    Approximately 1 month

    Outcome Measure

    Incidence of anti-drug antibodies (ADAs) against disitamab vedotin

    Measure Description

    Time Frame

    Through 30-37 days after the last study treatment; approximately 5 years

    Secondary Outcome Measures table for Clinical Trial

    Number of participants

    198

    Collaborators and investigators

    Sponsor: Seagen Inc.

    Collaborator: RemeGen Co., Ltd.

    This information is current as of September 4th 2024.
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    More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT06157892