A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors
- Conditions
- Breast NeoplasmsGastroesophageal Junction AdenocarcinomaHER2 Low Breast NeoplasmsHER2 Positive Breast NeoplasmsStomach NeoplasmsTriple Negative Breast NeoplasmsMetastatic Breast CancerMetastatic Gastric CancerAdvanced Breast CancerAdvanced Gastric Cancer
- Interventions
- Registration Number
- NCT06157892
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 172
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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation - Previously treated advanced GC/GEJC or breast cancer disitamab vedotin disitamab vedotin + tucatinib Dose Escalation - Previously treated advanced GC/GEJC or breast cancer tucatinib disitamab vedotin + tucatinib Dose Optimization - HER2-low and HER2+ LA/mBC disitamab vedotin disitamab vedotin + tucatinib Dose Optimization - HER2-low and HER2+ LA/mBC tucatinib disitamab vedotin + tucatinib Dose Optimization - HER2-low and HER2+ LA/mGC/GEJC disitamab vedotin disitamab vedotin + tucatinib Dose Optimization - HER2-low and HER2+ LA/mGC/GEJC tucatinib disitamab vedotin + tucatinib Dose Expansion - HER2-low LA/mBC disitamab vedotin disitamab vedotin + tucatinib Dose Expansion - HER2-low LA/mBC tucatinib disitamab vedotin + tucatinib Dose Expansion - HER2+ LA/mBC disitamab vedotin disitamab vedotin + tucatinib Dose Expansion - HER2+ LA/mBC tucatinib disitamab vedotin + tucatinib Dose Expansion - HER2-low LA/mGC/GEJC disitamab vedotin disitamab vedotin + tucatinib Dose Expansion - HER2-low LA/mGC/GEJC tucatinib disitamab vedotin + tucatinib Dose Expansion - HER2+ LA/mGC/GEJC disitamab vedotin disitamab vedotin + tucatinib Dose Expansion - HER2+ LA/mGC/GEJC tucatinib disitamab vedotin + tucatinib
- Primary Outcome Measures
Name Time Method Number of participants with dose limiting toxicities (DLTs) in dose escalation phase Up to 28 days Number of participants with adverse events (AEs) Through 30 days after the last study treatment; approximately 5 years 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
Number of participants with laboratory abnormalities Through 30-37 days after the last study treatment: approximately 5 years Number of participants with dose alterations 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 Approximately 3 years The proportion of participants with confirmed response (CR) or partial response (PR) according to RECIST v1.1.
- Secondary Outcome Measures
Name Time Method Duration of response (DOR) per RECIST v1.1 by investigator assessment Approximately 5 years 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
Disease control rate (DCR) per RECIST v1.1 by investigator assessment Approximately 5 years The proportion of participants with stable disease (SD) or confirmed CR or PR according to RECIST v1.1.
Progression free survival (PFS) per RECIST v1.1 by investigator assessment Approximately 5 years The time from the start of any study treatment (or randomization date for participants in dose optimization phase) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.
Overall survival (OS) Approximately 5 years The time from the start of any study treatment (or randomization date for participants in dose optimization phase) to the date of death due to any cause.
Pharmacokinetic (PK) parameter - Maximum concentration (Cmax) 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) Approximately 1 month Incidence of anti-drug antibodies (ADAs) against disitamab vedotin Through 30-37 days after the last study treatment; approximately 5 years
Trial Locations
- Locations (118)
Ecg Medica Sl
🇪🇸Valencia, Spain
Arizona Cancer Center / University of Arizona
🇺🇸Tucson, Arizona, United States
Banner-University Medical Center Tucson Campus
🇺🇸Tucson, Arizona, United States
The University of Arizona Cancer Center-North Campus Pharmacy, Attn: Kelly Myrdal
🇺🇸Tucson, Arizona, United States
The University of Arizona Cancer Center-Main
🇺🇸Tucson, Arizona, United States
Chao Family Comprehensive Cancer Center University of California Irvine
🇺🇸Orange, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
University of California, San Francisco | HDFCCC - Hematopoietic Malignancies
🇺🇸San Francisco, California, United States
UCLA Department of Medicine - Hematology & Oncology
🇺🇸Santa Monica, California, United States
Colorado West Healthcare System, dba Community Hospital
🇺🇸Grand Junction, Colorado, United States
Colorado West Healthcare, dba Grand Valley Oncology
🇺🇸Grand Junction, Colorado, United States
Danbury Hospital
🇺🇸Danbury, Connecticut, United States
The Whittingham Cancer Center / Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Moffitt Cancer Center - International Plaza
🇺🇸Tampa, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center - McKinley Campus
🇺🇸Tampa, Florida, United States
Moffitt McKinley Hospital
🇺🇸Tampa, Florida, United States
Moffitt Cancer Center at Wesley Chapel
🇺🇸Wesley Chapel, Florida, United States
Georgia Cancer Specialists - Athens
🇺🇸Athens, Georgia, United States
Georgia Cancer Specialists - Annex
🇺🇸Atlanta, Georgia, United States
Atlanta Cancer Care - Atlanta
🇺🇸Atlanta, Georgia, United States
Georgia Cancer Specialists-Northside
🇺🇸Atlanta, Georgia, United States
Northside Hospital, Inc.- Central Research Department
🇺🇸Atlanta, Georgia, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Georgia Cancer Specialists - Blairsville
🇺🇸Blairsville, Georgia, United States
Georgia Cancer Specialists - Canton
🇺🇸Canton, Georgia, United States
Atlanta Cancer Care - Cumming
🇺🇸Cumming, Georgia, United States
Georgia Cancer Specialists - Cumming
🇺🇸Cumming, Georgia, United States
Georgia Cancer Specialists - Decatur
🇺🇸Decatur, Georgia, United States
Suburban Hematology-Oncology Associates - Duluth
🇺🇸Duluth, Georgia, United States
Suburban Hematology-Oncology Associates- Lawrenceville
🇺🇸Lawrenceville, Georgia, United States
Georgia Cancer Specialists - Macon
🇺🇸Macon, Georgia, United States
Georgia Cancer Specialists - Marietta
🇺🇸Marietta, Georgia, United States
Memorial Hospital
🇺🇸Shiloh, Illinois, United States
Siteman Cancer Center - Shiloh
🇺🇸Shiloh, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital.
🇺🇸Boston, Massachusetts, United States
University of Texas Southwestern Medical Center - Simmons Cancer Center
🇺🇸Dallas, Texas, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute- Chestnut Hill
🇺🇸Newton, Massachusetts, United States
Siteman Cancer Center - West County
🇺🇸Creve Coeur, Missouri, United States
Siteman Cancer Center - North County
🇺🇸Florissant, Missouri, United States
Saint Luke's Cancer Institute LLC
🇺🇸Kansas City, Missouri, United States
St Lukes Hospital
🇺🇸Kansas City, Missouri, United States
Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Washington University in St Louis.
🇺🇸Saint Louis, Missouri, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - South County
🇺🇸Saint Louis, Missouri, United States
Siteman Cancer Center - St Peters
🇺🇸Saint Peters, Missouri, United States
Renown Oncology
🇺🇸Reno, Nevada, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
San Juan Oncology Associates
🇺🇸Farmington, New Mexico, United States
Memorial Sloan Kettering Cancer Center - Main Hospital
🇺🇸New York, New York, United States
Zangmeister Cancer Center
🇺🇸Columbus, Ohio, United States
Saint Francis Hospital / Bon Secours - South Carolina
🇺🇸Greenville, South Carolina, United States
Sarah Cannon Research Institute - Pharmacy
🇺🇸Nashville, Tennessee, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Parkland Health and Hospital System
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center Simmons Cancer Center - Redbird
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center Clinical Lab-Zale Lipshy University Hospital
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center-Simmons Cancer Center Pharmacy
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center-William P. Clements Jr. University Hospital
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Simmons Cancer Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
University of Texas Southwestern Medical Center Clinical Laboratory - Richardson/Plano
🇺🇸Richardson, Texas, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
🇺🇸Madison, Wisconsin, United States
Carbone Cancer Center / University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Peninsula & South Eastern Hematology and Oncology Group (PASO)
🇦🇺Frankston, Victoria, Australia
Slade Pharmacy Frankston
🇦🇺Frankston, Victoria, Australia
Slade Health
🇦🇺Mount Waverley, Victoria, Australia
BC Cancer Kelowna.
🇨🇦Kelowna, British Columbia, Canada
Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
University of Ottawa / Ottawa General Hospital
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
University Health Network, Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
A.O.U. Federico II
🇮🇹Napoli, Campania, Italy
Azienda Ospedaliera Universitaria (AOU) Federico II
🇮🇹Napoli, Campania, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Lombardia, Italy
Niguarda Ca' Granda Hospital
🇮🇹Milano, Lombardia, Italy
Humanitas Istituto Clinico Catanese
🇮🇹Misterbianco (CT), Sicilia, Italy
Azienda Ospedaliera Universitaria Integrata di Verona.
🇮🇹Verona, Veneto, Italy
Centro Ricerche Cliniche Di Verona Srl
🇮🇹Verona, Veneto, Italy
UOC Diagnostica per lmmagini e Radioterapia
🇮🇹Napoli, Italy
Dong-A University Hospital
🇰🇷Busan, Other, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Other, Korea, Republic of
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
St. Vincent's Hospital, The Catholic University of Korea
🇰🇷Suwon-si, Korea, Republic of
Quirén Salud Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari Vall d´Hebron
🇪🇸Barcelona, Spain
CETIR Grup Medic
🇪🇸Barcelona, Spain
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
Grupo Hospitalario QuironSalud
🇪🇸Erandio Bizkaia, Spain
L'Institut Catala d'Oncologia.
🇪🇸L'Hospitalet de Llobregat, Spain
Farmacia-Ensayos. Planta S - Hospital Universitario HM Sanchinarro-CIOCC-START Madrid
🇪🇸Madrid, Spain
START Madrid-CIOCC_Hospital HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
National Taiwan University Cancer Center
🇨🇳Taipei, Taiwan
The Royal Marsden Hospital
🇬🇧London, United Kingdom
St Bartholomew's Hospital
🇬🇧London, United Kingdom
The Royal Marsden NHS Foundation Trust (RM)
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom