A Study of SGN-B6A in Advanced Solid Tumors

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase 1 Study of SGN-B6A in Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04389632
• Other study ID #: SGNB6A-001
• Secondary ID: 2023-508469-34
• Status: Recruiting
• Phase: Phase 1
• Start date: June 8, 2020
• Est. completion date: October 31, 2028

Study information

• Verified date: May 2024
• Source: Seagen Inc.
• Contact: Seagen Trial Information Support
• Phone: 866-333-7436
• Email: clinicaltrials[@]seagen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 824
• Est. completion date: October 31, 2028
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Breast Neoplasms
• Carcinoma
• Carcinoma, Non-Small Cell Lung
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Cutaneous Squamous Cell Cancer
• Esophageal Adenocarcinoma
• Esophageal Squamous Cell Carcinoma
• Exocrine Pancreatic Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma
• Neoplasms
• Neoplasms, Squamous Cell
• Ovarian Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Stomach Neoplasms
• Urinary Bladder Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• sigvotatug vedotin
Administered into the vein (IV; intravenously)
• pembrolizumab
200mg every 3 weeks or 400mg every 6 weeks, given by IV
• cisplatin
75 mg/m2 every 3 weeks, given by IV
• carboplatin
AUC 5 mg/mL per min every 3 weeks, given by IV

Locations

Country	Name	City	State
France	Institut Gustave Roussy	Villejuif Cedex	Other
Spain	Hospital HM Nou Delfos	Barcelona	Other
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Other
Spain	Elche General University Hospital	Elche	Other
Spain	Hospital Universitario De Jerez	Jerez de la Frontera	Other
Spain	Hospital Universitario Ramon y Cajal Servicio de Oncologia Medica Oficina de Ensayos Clinicos	Madrid	Other
Spain	START Madrid-CIOCC_Hospital HM Sanchinarro	Madrid	Other
Spain	Hospital Universitario Marques de Valdecilla	Santander	Other
Switzerland	University Hospital Lausanne CHUV	Lausanne	Other
United Kingdom	Sarah Cannon Research Institute UK	London	Other
United Kingdom	The Royal Marsden Hospital (Surrey)	Sutton	Other
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Vista Oncology Inc PS	Olympia	Washington
United States	Florida Cancer Specialists - Lake Nona	Orlando	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Sanford Cancer Center	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Countries where clinical trial is conducted

United States,  France,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs)	Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.	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
Primary	Number of patients with laboratory abnormalities		Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Primary	Number of participants with dose-limiting toxicities (DLTs)		Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment	The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to RECIST v1.1.	Up to approximately 3 years
Secondary	Duration of objective response (DOR) per RECIST v1.1 by investigator assessment	The time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease (PD) or to death due to any cause	Up to approximately 3 years
Secondary	Progression-free survival (PFS) per RECIST v1.1 by investigator assessment	The time from the start of any study treatment to the first documentation of PD, or death due to any cause	Up to approximately 3 years
Secondary	Overall survival (OS)	The time from the start of any study treatment to the date of death due to any cause	Up to approximately 3 years
Secondary	Area under the concentration-time curve (AUC)	Pharmacokinetic (PK) endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Concentration at the end of infusion (Ceoi)	PK endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Maximum observed concentration (Cmax)	PK endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Time to maximum observed concentration (Tmax)	PK endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Trough concentration (Ctrough)	PK endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Apparent terminal elimination half-life (t1/2)	PK endpoint	Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years
Secondary	Number of participants with antidrug antibodies (ADAs)		Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years