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Combining disitamab vedotin with tucatinib for treating solid tumors

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

Phase 2 Interventional Seagen Inc. · NCT06157892

This study is testing a new combination of two drugs, disitamab vedotin and tucatinib, to see if it can help people with advanced breast or stomach cancer that has not responded to other treatments.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment172 (estimated)
Ages18 Years and up
SexAll
SponsorSeagen Inc. Industry-sponsored
Drugs / interventionssacituzumab, pembrolizumab, trastuzumab, pertuzumab, disitamab, tucatinib, chemotherapy
Locations141 sites (Tucson, Arizona and 140 other locations)
Trial IDNCT06157892 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of disitamab vedotin, an antibody drug conjugate, in combination with tucatinib for patients with locally advanced or metastatic breast and gastric cancers that express HER2. The study consists of a dose escalation phase to determine the optimal dosage and a subsequent optimization phase to assess safety and efficacy. Participants must have measurable disease and have experienced progression on standard therapies. The trial aims to establish a beneficial treatment regimen for patients with limited options.

Who should consider this trial

Good fit: Ideal candidates include individuals with locally advanced or metastatic breast or gastric cancer that express HER2 and have progressed on standard treatments.

Not a fit: Patients with early-stage cancer or those whose tumors do not express HER2 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced HER2-expressing solid tumors.

How similar studies have performed: Other studies have shown promising results with similar antibody drug conjugate approaches, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion 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 and Optimization Phase Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
* Locally-advanced, unresectable, or metastatic stage
* 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 intolerance to endocrine therapy or endocrine therapy refractory disease:

    * Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR
    * Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting
  * 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.
  * Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated.

Cohort B (HER2+ Breast Cancer) Inclusion Criteria

* 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 for advanced disease.
  * 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

Cohort C (HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma) Inclusion Criteria

* 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/GEJC
* Must not have received prior treatment with HER2 directed therapy

Cohort D (HER2+ LA/mGC/GEJC) Inclusion Criteria

* Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
* 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 plus fluoropyrimidine and platinum containing chemotherapy if no contraindication.
  * Prior T-DXd treatment is allowed
  * Prior PD1 inhibitor therapy is allowed
  * No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC

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

Where this trial is running

Tucson, Arizona and 140 other locations

+91 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Breast NeoplasmsGastroesophageal Junction AdenocarcinomaHER2 Low Breast NeoplasmsHER2 Positive Breast NeoplasmsStomach NeoplasmsTriple Negative Breast NeoplasmsMetastatic Breast CancerMetastatic Gastric Cancer
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.