Clinical trial NCT06157892: A Study of Disitamab Vedotin With Other Anticancer Drugs in Solid Tumors
Official title: A Phase 1b/2 Open-Label Study of Disitamab Vedotin in Combination With Other Anticancer Therapies in Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasms
Gastroesophageal Junction Adenocarcinoma
HER2 Low Breast Neoplasms
HER2 Positive Breast Neoplasms
Stomach Neoplasms
Triple Negative Breast Neoplasms
Metastatic Breast Cancer
Metastatic Gastric Cancer
Advanced Breast Cancer
Advanced Gastric Cancer
Keywords: Breast Cancer
Gastric Cancer
GC
GEJ
HER2-Low Breast Cancer
HER2-Positive Breast Cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: RemeGen Co., Ltd.
First posted: 2023-12-06
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Number of participants with dose limiting toxicities (DLTs) in dose escalation phase
timeFrame: Up to 28 days
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30 days after the last study treatment; approximately 5 years
measure: Number of participants with laboratory abnormalities
timeFrame: Through 30-37 days after the last study treatment: approximately 5 years
measure: Number of participants with dose alterations
timeFrame: Through 30-37 days after the last study treatment: approximately 5 years
measure: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Duration of response (DOR) per RECIST v1.1 by investigator assessment
timeFrame: Approximately 5 years
measure: Disease control rate (DCR) per RECIST v1.1 by investigator assessment
timeFrame: Approximately 5 years
measure: Progression free survival (PFS) per RECIST v1.1 by investigator assessment
timeFrame: Approximately 5 years
measure: Overall survival (OS)
timeFrame: Approximately 5 years
measure: Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)
timeFrame: Through 30-37 days after the last study treatment; approximately 5 years
measure: PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
timeFrame: Approximately 1 month
measure: Incidence of anti-drug antibodies (ADAs) against disitamab vedotin
timeFrame: Through 30-37 days after the last study treatment; approximately 5 years
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center / University of Arizona
state: Arizona
city: Tucson
country: United States
facility: Banner-University Medical Center Tucson Campus
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-North Campus Pharmacy, Attn: Kelly Myrdal
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-Main
state: Arizona
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center University of California Irvine
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco | HDFCCC - Hematopoietic Malignancies
state: California
city: Santa Monica
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: Grand Junction
country: United States
facility: Colorado West Healthcare System, dba Community Hospital
state: Colorado
city: Grand Junction
country: United States
facility: Colorado West Healthcare, dba Grand Valley Oncology
state: Colorado
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Norwalk
country: United States
facility: The Whittingham Cancer Center / Norwalk Hospital
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: Moffitt Cancer Center - International Plaza
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center - McKinley Campus
state: Florida
city: Tampa
country: United States
facility: Moffitt McKinley Hospital
state: Florida
city: Wesley Chapel
country: United States
facility: Moffitt Cancer Center at Wesley Chapel
state: Florida
city: Athens
country: United States
facility: Georgia Cancer Specialists - Athens
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists - Annex
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Cancer Care - Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Georgia Cancer Specialists-Northside
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital, Inc.- Central Research Department
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Blairsville
country: United States
facility: Georgia Cancer Specialists - Blairsville
state: Georgia
city: Canton
country: United States
facility: Georgia Cancer Specialists - Canton
state: Georgia
city: Cumming
country: United States
facility: Atlanta Cancer Care - Cumming
state: Georgia
city: Cumming
country: United States
facility: Georgia Cancer Specialists - Cumming
state: Georgia
city: Decatur
country: United States
facility: Georgia Cancer Specialists - Decatur
state: Georgia
city: Duluth
country: United States
facility: Suburban Hematology-Oncology Associates - Duluth
state: Georgia
city: Lawrenceville
country: United States
facility: Suburban Hematology-Oncology Associates- Lawrenceville
state: Georgia
city: Macon
country: United States
facility: Georgia Cancer Specialists - Macon
state: Georgia
city: Marietta
country: United States
facility: Georgia Cancer Specialists - Marietta
state: Georgia
city: Shiloh
country: United States
facility: Memorial Hospital
state: Illinois
city: Shiloh
country: United States
facility: Siteman Cancer Center - Shiloh
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Newton
country: United States
facility: Dana Farber Cancer Institute- Chestnut Hill
state: Massachusetts
city: Creve Coeur
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Florissant
country: United States
facility: Siteman Cancer Center - North County
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute LLC
state: Missouri
city: Kansas City
country: United States
facility: St Lukes Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St Louis.
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St Peters
state: Missouri
city: Reno
country: United States
facility: Renown Oncology
state: Nevada
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - Main Hospital
state: New York
city: Columbus
country: United States
facility: Zangmeister Cancer Center
state: Ohio
city: Greenville
country: United States
facility: Saint Francis Hospital / Bon Secours - South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Pharmacy
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Parkland Health and Hospital System
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Simmons Cancer Center - Redbird
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Simmons Cancer Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center Clinical Lab-Zale Lipshy University Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center-Simmons Cancer Center Pharmacy
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center-William P. Clements Jr. University Hospital
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: University of Texas Southwestern Simmons Cancer Center - Fort Worth
state: Texas
city: Richardson
country: United States
facility: University of Texas Southwestern Medical Center Clinical Laboratory - Richardson/Plano
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
state: Wisconsin
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Richmond
country: Australia
facility: Peninsula & South Eastern Hematology and Oncology Group (PASO)
state: South Australia
city: Frankston
country: Australia
facility: Peninsula & South Eastern Hematology and Oncology Group (PASO)
state: Victoria
city: Frankston
country: Australia
facility: Slade Pharmacy Frankston
state: Victoria
city: Mount Waverley
country: Australia
facility: Slade Health
state: Victoria
city: Kelowna
country: Canada
facility: BC Cancer Kelowna.
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa / Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Ontario
city: Napoli
country: Italy
facility: A.O.U. Federico II
state: Campania
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) Federico II
state: Campania
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
state: Campania
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Lombardia
city: Milano
country: Italy
facility: Niguarda Ca' Granda Hospital
state: Lombardia
city: Misterbianco (CT)
country: Italy
facility: Humanitas Istituto Clinico Catanese
state: Sicilia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona.
state: Veneto
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona Srl
state: Veneto
city: Napoli
country: Italy
facility: UOC Diagnostica per lmmagini e Radioterapia
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
state: Other
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Other
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Suwon-si
country: Korea, Republic of
facility: St. Vincent's Hospital, The Catholic University of Korea
city: Barcelona
country: Spain
facility: Quirén Salud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron
city: Barcelona
country: Spain
facility: CETIR Grup Medic
city: Bilbao
country: Spain
facility: Hospital Universitario de Basurto
city: Erandio Bizkaia
country: Spain
facility: Grupo Hospitalario QuironSalud
city: L'Hospitalet de Llobregat
country: Spain
facility: L'Institut Catala d'Oncologia.
city: Madrid
country: Spain
facility: Farmacia-Ensayos. Planta S - Hospital Universitario HM Sanchinarro-CIOCC-START Madrid
city: Madrid
country: Spain
facility: START Madrid-CIOCC_Hospital HM Sanchinarro
city: Valencia
country: Spain
facility: Ecg Medica Sl
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Cancer Center
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
state: Surrey
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust (RM)
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: