Clinical trial NCT04389632: A Study of SGN-B6A in Advanced Solid Tumors
Official title: A Phase 1 Study of SGN-B6A in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small Cell Lung
Squamous Cell Carcinoma of Head and Neck
HER2 Negative Breast Neoplasms
Esophageal Squamous Cell Carcinoma
Esophageal Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Ovarian Neoplasms
Cutaneous Squamous Cell Cancer
Exocrine Pancreatic Adenocarcinoma
Urinary Bladder Neoplasms
Uterine Cervical Neoplasms
Stomach Neoplasms
Keywords: NSCLC
HNSCC
cSCC
ESCC
EAC
GEJ
HGSOC
Advanced HER2-Negative Breast Cancer
High Grade Serous Ovarian Cancer
Non-Small Cell Lung Cancer
Head and Neck Squamous Cell Cancer
Esophageal Cancer
Bladder Cancer
Cervical Cancer
Gastric Cancer
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-15
Enrollment: 1006
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This trial will look at a drug called sigvotatug vedotin (SGN-B6A) alone and with pembrolizumab, with or without chemotherapy, to find out whether it is safe for people who have solid tumors. It will study sigvotatug vedotin to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether sigvotatug vedotin works to treat solid tumors.

The study will have four parts.

* Part A of the study will find out how much sigvotatug vedotin should be given to participants.
* Part B will use the dose found in Part A to find out how safe sigvotatug vedotin is and if it works to treat solid tumors.
* Part C of the study will find out how safe sigvotatug vedotin is in combination with these other drugs.
* Part D will include people who have not received treatment. This part of the study will find out how safe sigvotatug vedotin is in combination with these other drugs and if these combinations work to treat solid tumors.
* In Parts C and D, participants will receive sigvotatug vedotin with either:

  * Pembrolizumab or,
  * Pembrolizumab and carboplatin, or
  * Pembrolizumab and cisplatin.


Eligibility criteria: Inclusion Criteria:

* Disease indication

  * Participants must have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the tumor types listed below (dependent on study part).

    * Non-small cell lung cancer (NSCLC)
    * Head and neck squamous cell cancer (HNSCC)
    * Advanced HER2-negative breast cancer
    * Esophageal squamous cell carcinoma (ESCC)
    * Esophageal/Gastro-esophageal junction adenocarcinoma (EAC/GEJ)
    * Cutaneous squamous cell cancer (cSCC)
    * Exocrine pancreatic adenocarcinoma
    * Bladder cancer
    * Cervical cancer
    * Gastric cancer
    * High grade serous ovarian cancer (HGSOC)
  * Part A only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies and should have no appropriate standard-of-care therapeutic options.
  * Part B only: Participants must have disease that is relapsed or refractory or be intolerant to standard-of-care therapies. Participants must have received platinum-based therapy and a PD-1/PD-(L)1 inhibitor, if applicable and available.
  * Part C only: For pembrolizumab combination cohorts, participants must be eligible for pembrolizumab per local standard of care. For pembrolizumab with cisplatin or carboplatin, participants must be eligible for both pembrolizumab and the platinum agent per local standard of care. Participants must be treatment naïve for locally advanced or metastatic systemic therapy (prior definitively intended or \[neo\]adjuvant therapy is allowed).
  * Part D only: Participants must be treatment naïve for locally advanced or metastatic systemic therapy.
* Participants enrolled in the following study parts should have a tumor site accessible for biopsy and agree to biopsy as follows:

  * Disease-specific expansion cohorts (Part B and Part D): A baseline fresh tumor biopsy is required. An archival biopsy collected within 90 days prior to first dose of study drug may be used.
  * Biology expansion cohort: pretreatment biopsy and on-treatment (Cycle 1) biopsy
* An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Measurable disease per the RECIST v1.1 at baseline

Exclusion Criteria

* History of another malignancy within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
* Known active central nervous system metastases. Participants with previously treated brain metastases may participate provided they:

  * are clinically stable for at least 4 weeks prior to study entry after brain metastasis treatment,
  * have no new or enlarging brain metastases, and
  * are off of corticosteroids prescribed for symptoms associated with brain metastases for at least 7 days prior to first dose of study drug.
* Carcinomatous meningitis
* Previous receipt of an MMAE-containing agent or an agent targeting integrin beta-6
* Pre-existing neuropathy Grade 1 or greater per the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0) for Parts C and D cohorts with cisplatin or carboplatin; Grade 2 or greater per the NCI CTCAE v5.0 for all other cohorts
* Any uncontrolled Grade 3 or higher (per NCI CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of sigvotatug vedotin.

  * Routine antimicrobial prophylaxis is permitted
* Grade ≥3 pulmonary disease unrelated to underlying malignancy. This includes clinically severe pulmonary function compromise resulting from clinically significant pulmonary illnesses
* Part C and D: Prior therapy with a PD-1 inhibitor, anti-PD-(L)1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor and was discontinued from that treatment due to a Grade 3 or higher immune-mediated adverse event (IMAE).
* History of noninfectious interstitial lung disease (ILD) or pneumonitis that required steroids, current ILD or pneumonitis, or suspected ILD or pneumonitis that cannot be ruled out by imaging at screening
* Known diffusing capacity of the lung for carbon monoxide (DLCO; adjusted for hemoglobin) \<50% predicted

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin. For participants receiving pembrolizumab up to 90 days after last dose of pembrolizumab; up to 3 years
measure: Number of patients with laboratory abnormalities
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary outcomes:
measure: Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment
timeFrame: Up to approximately 3 years
measure: Duration of objective response (DOR) per RECIST v1.1 by investigator assessment
timeFrame: Up to approximately 3 years
measure: Progression-free survival (PFS) per RECIST v1.1 by investigator assessment
timeFrame: Up to approximately 3 years
measure: Overall survival (OS)
timeFrame: Up to approximately 3 years
measure: Area under the concentration-time curve (AUC)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Concentration at the end of infusion (Ceoi)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Maximum observed concentration (Cmax)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Time to maximum observed concentration (Tmax)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Trough concentration (Ctrough)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
measure: Number of participants with antidrug antibodies (ADAs)
timeFrame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology
state: Alaska
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Springdale
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: Fullerton
country: United States
facility: Providence St. Jude Medical Center Virginia K Crosson and Infusion Center
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Research Center, LLC
state: California
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Department of Medicine-Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Department of Medicine - Hematology & Oncology
state: California
city: Torrance
country: United States
facility: Cancer AND Blood Specialty Clinic
state: California
city: Hollywood
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Orlando
country: United States
facility: Florida cancer Specialists
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West
state: Florida
city: Calumet City
country: United States
facility: Ingalls Family Care Center
state: Illinois
city: Chicago
country: United States
facility: UChicago Medicine - River East
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Flossmoor
country: United States
facility: UChicago Medicine at Ingalls - Flossmoor
state: Illinois
city: Harvey
country: United States
facility: UChicago Medicine Ingalls Memorial
state: Illinois
city: New Lenox
country: United States
facility: University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
state: Illinois
city: Orland Park
country: United States
facility: The University of Chicago Medicine Center for Advanced Care Orland Park
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University - Simmons Cancer Institute
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic Radiology - 800 Building
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic Radiology - Main Campus
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic, LLP
state: Illinois
city: Tinley Park
country: United States
facility: UChicago Medicine at Ingalls - Tinley Park
state: Illinois
city: Crown Point
country: United States
facility: UChicago Medicine - Northwest Indiana
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network Investigational Drug Services
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Fairway
country: United States
facility: The University of Kansas Cancer Center, Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Medical Center Medical Office Building
state: Kansas
city: Kansas City
country: United States
facility: University of Kansas Hospital Cambridge North Tower A
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center - Indian Creek Campus
state: Kansas
city: Westwood
country: United States
facility: The University of Kansas Cancer Center - Westwood
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center,East Campus Research Pharmacy
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
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: Coon Rapids
country: United States
facility: Allina Health Cancer Institute - Mercy Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute - Abbott Northwestern Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Babylon
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Bronx
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: New Hyde Park
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: New York
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: CUIMC Research Pharmacy
state: New York
city: Patchogue
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Port Jefferson Station
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Riverhead
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Shirley
country: United States
facility: New York Cancer and Blood Specialists
state: New York
city: Shirley
country: United States
facility: North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University at Stephenson Cancer Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: OU Health University of Oklahoma Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center (chemo location)
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Portland
country: United States
facility: Providence Cancer Institute Franz Clinic
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Oncology and Hematology Care Clinic - Westside
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center- Investigational Drug Services
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center
state: South Dakota
city: Houston
country: United States
facility: Oncology Consultants, PA
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, PA.
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, PA
state: Texas
city: Houston
country: United States
facility: The University of Texas M.D. Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: Tranquil Clinical Research & Consulting Services, LLC
state: Texas
city: Irving
country: United States
facility: US Oncology Investigational Product Center (IPC)
state: Texas
city: Pearland
country: United States
facility: Houston Medical Imaging
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center
state: Texas
city: Tyler
country: United States
facility: UT Health East Texas Hope Cancer Center
state: Texas
city: Webster
country: United States
facility: Tranquility Research
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Olympia
country: United States
facility: American Oncology Network Vista Oncology Division-West office
state: Washington
city: Olympia
country: United States
facility: American Oncology Network Vista Oncology Division-East office
state: Washington
city: Olympia
country: United States
facility: Vista Oncology Inc PS
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialities, PLLC
state: Washington
city: Villejuif Cedex
country: France
facility: Pharmacy Gustave Roussy
state: Agrigento
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Other
city: Angers
country: France
facility: Center Hospitalier Universitaire d' Angers
city: Moselle
country: France
facility: Institut de Cancérologie de Lorraine
city: Nice Cedex 2
country: France
facility: Centre de Lutte contre le Cancer (CLCC) - Centre Antoine Lacassagne
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Villejuif Cedex
country: France
facility: lnstitut Gustave Roussy, Departement d'lnnovation Therapeutique et d'Essais Precoces (DITEP)
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Madrid
country: Spain
facility: Farmacia Ensayos Hospital HM Universitario Sanchinarro
state: Agrigento
city: Elche
country: Spain
facility: Elche General University Hospital
state: Alicante
city: Santander
country: Spain
facility: Equipo de Farmacia Oncológica- Ensayos Clínicos Servicio de Farmacia Hospital Universitario Marqués
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos
state: Catalonia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Cataluna
city: Madrid
country: Spain
facility: START Madrid-CIOCC_Hospital HM Sanchinarro
state: Comunidad DE Madrid
city: Barcelona
country: Spain
facility: NEXT Oncology Barcelona - IOB - Hospital Quironsalud Barcelona
state: OTH
city: Barcelona
country: Spain
facility: Farmacia Ensayos clínicos, Unidad START Barcelona
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos - START Barcelona
city: Barcelona
country: Spain
facility: Hospital Quiron Salud Barcelona
city: Barcelona
country: Spain
facility: Area general-Planta Baixa | Unitat d'investigacio en terapia Molecular del Cancer "la Caixa"
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Elche
country: Spain
facility: Elche General University Hospital
city: Jerez de la Frontera
country: Spain
facility: Hospital Universitario De Jerez
city: Jerez de la Frontera
country: Spain
facility: UGC Farmacia Ensayos clinicos - Hospital Universitario de Jerez
city: Jerez de la Frontera
country: Spain
facility: Hospital Universitario de Jerez
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Servicio de Radiologia Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
city: Madrid
country: Spain
facility: Hospital HM Sanchinarro, START-Madrid-CIOCC
city: Malaga
country: Spain
facility: Quironsalud Malaga
city: Malaga
country: Spain
facility: Hospital Quiron Salud Malaga
city: Lausanne
country: Switzerland
facility: CHUV Service de Pharmacie
state: Agrigento
city: Chur
country: Switzerland
facility: Kantonsspital Graubunden
city: Lausanne
country: Switzerland
facility: University Hospital Lausanne CHUV
city: Lausanne
country: Switzerland
facility: CHUV - Service de pharmacie BH-04, Essais cliniques
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Medical University Hospital
state: R.o.c.
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital.
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Queensland
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute
city: London
country: United Kingdom
facility: Diagnostic centre
city: London
country: United Kingdom
facility: The Harley Street Clinic
city: London
country: United Kingdom
facility: Radiology
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: