Dysautonomia International

A Study of Sigvotatug Vedotin in Advanced Solid Tumors

Purpose

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.

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

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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. - In Part D, participants with untreated, asymptomatic CNS metastases smaller than 1 cm may be enrolled without definitive treatment as long as they have no neurological symptoms, no or minimal surrounding edema, and no requirements for corticosteroids. - 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 - Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: N/A
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part A: Dose escalation	sigvotatug vedotin monotherapy	Drug: sigvotatug vedotin Administered into the vein (IV; intravenously) Other names: SGN-B6A PF-08046047
Experimental Part B: Dose expansion	sigvotatug vedotin monotherapy	Drug: sigvotatug vedotin Administered into the vein (IV; intravenously) Other names: SGN-B6A PF-08046047
Experimental Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC	sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)	Drug: sigvotatug vedotin Administered into the vein (IV; intravenously) Other names: SGN-B6A PF-08046047 Drug: pembrolizumab 200mg every 3 weeks or 400mg every 6 weeks, given by IV Other names: Keytruda Drug: cisplatin 75 mg/m2 every 3 weeks, given by IV Drug: carboplatin AUC 5 mg/mL per min every 3 weeks, given by IV
Experimental Part D: sigvotatug vedotin combination therapy in 1L NSCLC	sigvotatug vedotin + pembrolizumab +/- (carboplatin)	Drug: sigvotatug vedotin Administered into the vein (IV; intravenously) Other names: SGN-B6A PF-08046047 Drug: pembrolizumab 200mg every 3 weeks or 400mg every 6 weeks, given by IV Other names: Keytruda Drug: carboplatin AUC 5 mg/mL per min every 3 weeks, given by IV
Experimental Part D: sigvotatug vedotin combination therapy in 1L HNSCC	sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)	Drug: sigvotatug vedotin Administered into the vein (IV; intravenously) Other names: SGN-B6A PF-08046047 Drug: pembrolizumab 200mg every 3 weeks or 400mg every 6 weeks, given by IV Other names: Keytruda Drug: cisplatin 75 mg/m2 every 3 weeks, given by IV Drug: carboplatin AUC 5 mg/mL per min every 3 weeks, given by IV

Recruiting Locations

Alaska Oncology and Hematology
Anchorage, Alaska 99508

Highlands Oncology Group
Fayetteville, Arkansas 72703

Highlands Oncology Group
Rogers, Arkansas 72758

Highlands Oncology Group
Springdale, Arkansas 72762

Providence Medical Foundation
Anaheim, California 92805

Providence Medical Foundation
Fullerton, California 92835

Providence St. Jude Medical Center Virginia K Crosson and Infusion Center
Fullerton, California 92835

Ronald Reagan UCLA Medical Center
Los Angeles, California 90095

The Regents of the University of California
Los Angeles, California 90095

UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California 90095

UCLA Department of Medicine - Hematology & Oncology
Santa Monica, California 90404

American Oncology Partners, PA. a Florida professional service corporation, d/b/a Vista Oncology
Fort Myers, Florida 33913

Florida Cancer Specialists & Research Institute, LLC
Fort Myers, Florida 33916

Memorial Cancer Institute
Hollywood, Florida 33021

Memorial Healthcare System
Hollywood, Florida 33021

Florida Cancer Specialists
Orlando, Florida 32827

Memorial Cancer Institute at Memorial Hospital West
Pembroke Pines, Florida 33028

Memorial Hospital West
Pembroke Pines, Florida 33028

Ingalls Family Care Center
Calumet City, Illinois 60409

UChicago Medicine - River East
Chicago, Illinois 60611

The University Of Chicago
Chicago, Illinois 60637

University of Chicago Medical Center
Chicago, Illinois 60637

UChicago Medicine at Ingalls - Flossmoor
Flossmoor, Illinois 60422

UChicago Medicine Ingalls Memorial
Harvey, Illinois 60426

University of Chicago Comprehensive Cancer Center at Silver Cross Hospital
New Lenox, Illinois 60451

The University of Chicago Medicine Center for Advanced Care Orland Park
Orland Park, Illinois 60462

Southern Illinois University - Simmons Cancer Institute
Springfield, Illinois 62702

Springfield Clinic Radiology - 800 Building
Springfield, Illinois 62702

Springfield Clinic
Springfield, Illinois 62702

Springfield Clinic Main Campus
Springfield, Illinois 62703

Springfield Clinic Radiology - Main Campus
Springfield, Illinois 62703

Springfield Memorial Hospital
Springfield, Illinois 62781

UChicago Medicine at Ingalls - Tinley Park
Tinley Park, Illinois 60477

UChicago Medicine - Northwest Indiana
Crown Point, Indiana 46307

Fort Wayne Medical Oncology and Hematology, Inc
Fort Wayne, Indiana 46804

Community Health Network, Inc
Indianapolis, Indiana 46219

Community Health Network, Inc.
Indianapolis, Indiana 46227

Community Health Network Investigational Drug Services
Indianapolis, Indiana 46250

Community Health Network, Inc.
Indianapolis, Indiana 46250

Community Health Network
Indianapolis, Indiana 46256

The University of Kansas Cancer Center, Investigational Drug Services
Fairway, Kansas 66205

The University of Kansas Clinical Research Center
Fairway, Kansas 66205

The University of Kansas Hospital
Kansas City, Kansas 66160

The University of Kansas Medical Center Medical Office Building
Kansas City, Kansas 66160

University of Kansas Hospital Cambridge North Tower A
Kansas City, Kansas 66160

University of Kansas Medical Center Research Institute
Kansas City, Kansas 66160

The University of Kansas Cancer Center - Indian Creek Campus
Overland Park, Kansas 66211

The University of Kansas Cancer Center - Westwood
Westwood, Kansas 66205

University of Kansas Cancer Center
Westwood, Kansas 66205

Massachusetts General Hospital
Boston, Massachusetts 02114

Brigham & Women's Hospital
Boston, Massachusetts 02115

Beth Israel Deaconess Medical Center,East Campus Research Pharmacy
Boston, Massachusetts 02215

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215

Dana Farber Cancer Institute
Boston, Massachusetts 02215

Dana-Farber Cancer Institute - Chestnut Hill
Newton, Massachusetts 02467

Allina Health Cancer Institute - Mercy Hospital
Coon Rapids, Minnesota 55433

Allina Health Cancer Institute - Abbott Northwestern Hospital
Minneapolis, Minnesota 55407

Allina Health Cancer Institute
Saint Paul, Minnesota 55102

Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada 89169

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Babylon, New York 11702

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Brooklyn, New York 11210

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
New Hyde Park, New York 11042

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
New York, New York 10028

Columbia University Irving Medical Center
New York, New York 10032

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Patchogue, New York 11772

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Port Jefferson Station, New York 11776

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Riverhead, New York 11901

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
Shirley, New York 11967

North Shore Hematology Oncology Associates P.C. DBA New York Cancer and Blood Specialists
The Bronx, New York 10469

OU Health University of Oklahoma Medical Center
Oklahoma City, Oklahoma 73104

Stephenson Cancer Center (chemo location)
Oklahoma City, Oklahoma 73104

University of Oklahoma Health Science Center
Oklahoma City, Oklahoma 73104

Providence Cancer Institute Franz Clinic
Portland, Oregon 97213

Providence Oncology and Hematology Care Clinic - Westside
Portland, Oregon 97225

Providence St. Vincent Medical Center- Investigational Drug Services
Portland, Oregon 97225

Providence St. Vincent Medical Center
Portland, Oregon 97225

Sanford Cancer Center
Sioux Falls, South Dakota 57104

Sanford Research
Sioux Falls, South Dakota 57104

Sanford USD Medical Center
Sioux Falls, South Dakota 57105

US Oncology Research LLC
Nashville, Tennessee 37203

Oncology Consultants, PA
Houston, Texas 77024

Oncology Consultants, PA.
Houston, Texas 77030

The University of Texas M.D. Anderson Cancer Center
Houston, Texas 77030

US Oncology Investigational Product Center (IPC)
Irving, Texas 75063

UT Health East Texas HOPE Cancer Center
Tyler, Texas 75701

UT Health East Texas Hope Cancer Center
Tyler, Texas 75708

Virginia Cancer Specialists
Fairfax, Virginia 22031

Swedish Cancer Institute - Edmonds Campus
Edmonds, Washington 98026

Swedish Cancer Institute Edmonds Campus
Edmonds, Washington 98026

American Oncology Network Vista Oncology Division-West office
Olympia, Washington 98502

American Oncology Network Vista Oncology Division-East office
Olympia, Washington 98506

Swedish Cancer Institute
Seattle, Washington 98104

Swedish Medical Center
Seattle, Washington 98122

More Details

Status: Recruiting
Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com