RecruitingInterventionalPhase 2

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

NCT ID: NCT06157892Sponsor: Seagen, a wholly owned subsidiary of PfizerLast updated: 2026-05-05

Summary

This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer. Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2. This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®. This study will test how safe and how well DV with tucatinib works for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.

Detailed description

This clinical trial is to evaluate disitamab vedotin in combination with tucatinib in subjects with LA/metastatic breast cancer or gastric cancer/GEJC that express HER2. The study has a dose escalation phase evaluating disitamab vedotin plus tucatinib followed by a dose optimization phase. The 2 dose levels identified in the dose escalation phase will be assessed in the optimization phase for both safety and efficacy in HER2-expressing LA/mBC and LA/mGC/GEJC. Once the safety and efficacy profile of disitamab vedotin plus tucatinib has been established and a disitamab vedotin dose with the optimum benefit/risk ratio has been determined the disitamab vedotin plus tucatinib combination therapy will be evaluated in an expansion phase with 4 expansion cohorts in subjects with HER2-low LA/mGC/GEJC, HER2+ LA/mGC/GEJC, HER2-low LA/mBC, and HER2+ LA/mBC.

Arms & interventions

Drugdisitamab vedotin
Given into the vein (IV; intravenous)
Drugtucatinib
300mg given twice daily by mouth (orally)

Outcome measures

Primary

Number of participants with dose limiting toxicities (DLTs) in dose escalation phase
Time frame: Up to 28 days
Number of participants with adverse events (AEs)
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
Number of participants with laboratory abnormalities
Time frame: Through 30-37 days after the last study treatment: approximately 5 years
Number of participants with dose alterations
Time frame: Through 30-37 days after the last study treatment: approximately 5 years
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
The proportion of participants with confirmed response (CR) or partial response (PR) according to RECIST v1.1.
Time frame: Approximately 3 years

Secondary

Duration of response (DOR) per RECIST v1.1 by investigator assessment
Time frame: Approximately 5 years
Disease control rate (DCR) per RECIST v1.1 by investigator assessment
Time frame: Approximately 5 years
Progression free survival (PFS) per RECIST v1.1 by investigator assessment
Time frame: Approximately 5 years
Overall survival (OS)
Time frame: Approximately 5 years
Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)
Time frame: Through 30-37 days after the last study treatment; approximately 5 years
PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
Time frame: Approximately 1 month
Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
Time frame: Through 30-37 days after the last study treatment; approximately 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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

Study locations (82)

Banner-University Medical Center Tucson Campus

Tucson, Arizona, 85704

Recruiting

Banner-University Medical Center Tucson Campus

Tucson, Arizona, 85719

Recruiting

The University of Arizona Cancer Center-North Campus Pharmacy, Attn: Kelly Myrdal

Tucson, Arizona, 85719

Recruiting

University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719

Recruiting

The University of Arizona Cancer Center-Main

Tucson, Arizona, 85724

Recruiting

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868

Recruiting

UC Irvine Medical Center

Orange, California, 92868

Recruiting

University of California, San Francisco | HDFCCC - Hematopoietic Malignancies

San Francisco, California, 94158

Recruiting

UCLA Department of Medicine - Hematology & Oncology

Santa Monica, California, 90404

Recruiting

UCLA Hematology/Oncology - Parkside

Santa Monica, California, 90404

Recruiting

Colorado West Healthcare System, dba Community Hospital

Grand Junction, Colorado, 81505

Not Yet Recruiting

Colorado West Healthcare, dba Grand Valley Oncology

Grand Junction, Colorado, 81505

Not Yet Recruiting

Danbury Hospital

Danbury, Connecticut, 06810

Not Yet Recruiting

Praxair Cancer Center / Danbury Hospital

Danbury, Connecticut, 06810

Recruiting

The Whittingham Cancer Center / Norwalk Hospital

Norwalk, Connecticut, 06856

Not Yet Recruiting

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007

Recruiting

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007

Recruiting

Moffitt Cancer Center - International Plaza

Tampa, Florida, 33607

Recruiting

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

Recruiting

Moffitt Cancer Center - McKinley Campus

Tampa, Florida, 33612

Recruiting

Moffitt McKinley Hospital

Tampa, Florida, 33612

Recruiting

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, Florida, 33544

Recruiting

Georgia Cancer Specialists - Athens

Athens, Georgia, 30606

Recruiting

Georgia Cancer Specialists - Annex

Atlanta, Georgia, 30341

Recruiting

Atlanta Cancer Care - Atlanta

Atlanta, Georgia, 30342

Recruiting

Georgia Cancer Specialists-Northside

Atlanta, Georgia, 30342

Recruiting

Northside Hospital, Inc.- Central Research Department

Atlanta, Georgia, 30342

Recruiting

Northside Hospital

Atlanta, Georgia, 30342

Recruiting

Georgia Cancer Specialists - Blairsville

Blairsville, Georgia, 30512

Recruiting

Georgia Cancer Specialists - Canton

Canton, Georgia, 30115

Recruiting

Atlanta Cancer Care - Cumming

Cumming, Georgia, 30041

Recruiting

Georgia Cancer Specialists - Cumming

Cumming, Georgia, 30041

Recruiting

Georgia Cancer Specialists - Decatur

Decatur, Georgia, 30033

Recruiting

Suburban Hematology-Oncology Associates - Duluth

Duluth, Georgia, 30096

Recruiting

Suburban Hematology-Oncology Associates- Lawrenceville

Lawrenceville, Georgia, 30046

Recruiting

Georgia Cancer Specialists - Macon

Macon, Georgia, 31217

Recruiting

Georgia Cancer Specialists - Marietta

Marietta, Georgia, 30060

Recruiting

Memorial Hospital

Shiloh, Illinois, 62269

Recruiting

Siteman Cancer Center - Shiloh

Shiloh, Illinois, 62269

Recruiting

Massachusetts General Hospital.

Boston, Massachusetts, 02114

Recruiting

Brigham and Women's Hospital

Boston, Massachusetts, 02115

Recruiting

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Dana Farber Cancer Institute- Chestnut Hill

Newton, Massachusetts, 02459

Recruiting

Siteman Cancer Center - St Peters

City of Saint Peters, Missouri, 63376

Recruiting

Siteman Cancer Center - West County

Creve Coeur, Missouri, 63141

Recruiting

Siteman Cancer Center - North County

Florissant, Missouri, 63031

Recruiting

Saint Luke's Cancer Institute LLC

Kansas City, Missouri, 64111

Recruiting

Saint Luke's Hospital Investigational Pharmacy

Kansas City, Missouri, 64111

Recruiting

Barnes-Jewish Hospital

St Louis, Missouri, 63110

Recruiting

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, 63110

Recruiting

Washington University School of Medicine

St Louis, Missouri, 63110

Recruiting

Siteman Cancer Center - South County

St Louis, Missouri, 63129

Recruiting

Renown Regional Medical Center

Reno, Nevada, 89502

Recruiting

MSK Basking Ridge

Basking Ridge, New Jersey, 07920

Recruiting

MSK Monmouth.

Middletown, New Jersey, 07748

Recruiting

MSK Bergen.

Montvale, New Jersey, 07645

Recruiting

San Juan Oncology Associates

Farmington, New Mexico, 87401

Terminated

MSK Commack.

Commack, New York, 11725

Recruiting

MSK Westchester.

Harrison, New York, 10604

Recruiting

Investigational Drug Service

Long Island City, New York, 11101

Recruiting

Memorial Sloan Kettering Cancer Center - Main Hospital

New York, New York, 10065

Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Recruiting

MSK Nassau.

Uniondale, New York, 11553

Recruiting

Zangmeister Cancer Center

Columbus, Ohio, 43219

Recruiting

Saint Francis Hospital / Bon Secours - South Carolina

Greenville, South Carolina, 29607

Recruiting

Sarah Cannon Research Institute - Pharmacy

Nashville, Tennessee, 37203

Not Yet Recruiting

SCRI Oncology Partners

Nashville, Tennessee, 37203

Not Yet Recruiting

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Not Yet Recruiting

Parkland Health and Hospital System

Dallas, Texas, 75235

Not Yet Recruiting

University of Texas Southwestern Medical Center - Simmons Cancer Center

Dallas, Texas, 75235

Not Yet Recruiting

University of Texas Southwestern Medical Center-Simmons Cancer Center Pharmacy

Dallas, Texas, 75235

Not Yet Recruiting

University of Texas Southwestern Medical Center Simmons Cancer Center - Redbird

Dallas, Texas, 75237

Not Yet Recruiting

University of Texas Southwestern Medical Center Clinical Lab-Zale Lipshy University Hospital

Dallas, Texas, 75390

Not Yet Recruiting

University of Texas Southwestern Medical Center-William P. Clements Jr. University Hospital

Dallas, Texas, 75390

Not Yet Recruiting

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

Not Yet Recruiting

University of Texas Southwestern Simmons Cancer Center - Fort Worth

Fort Worth, Texas, 76104

Not Yet Recruiting

University of Texas Southwestern Medical Center Simmons Cancer Center - Richardson/Plano

Richardson, Texas, 75080

Not Yet Recruiting

Harborview Medical Center

Seattle, Washington, 98104

Recruiting

Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109

Recruiting

University of Washington Medical Center

Seattle, Washington, 98195

Recruiting

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718

Recruiting

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, 53792

Recruiting