A Study of SGN-B6A in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT04389632
• Recruitment Status: Recruiting
• First Posted: May 15, 2020
• Last Update Posted: May 14, 2024
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: May 12, 2020
• First Posted Date: May 15, 2020
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: June 8, 2020
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2024)

• Number of participants with adverse events (AEs) [ Time Frame: 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 ]
  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.
• Number of patients with laboratory abnormalities [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
• Number of participants with dose-limiting toxicities (DLTs) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]

Original Primary Outcome Measures (submitted: May 12, 2020)

• Number of participants with treatment-emergent adverse events (AEs) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of participants with Grade 3 or higher AEs [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of participants with serious AEs [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of participants with treatment-related AEs [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of patients with laboratory abnormalities [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of participants with DLTs [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Number of participants with a DLT at each dose level [ Time Frame: Up to 21 days ]

Current Secondary Outcome Measures (submitted: February 9, 2024)

• Confirmed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
  The proportion of participants with complete response (CR) or partial response (PR) which is subsequently confirmed as assessed according to RECIST v1.1.
• Duration of objective response (DOR) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
  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
• Progression-free survival (PFS) per RECIST v1.1 by investigator assessment [ Time Frame: Up to approximately 3 years ]
  The time from the start of any study treatment to the first documentation of PD, or death due to any cause
• Overall survival (OS) [ Time Frame: Up to approximately 3 years ]
  The time from the start of any study treatment to the date of death due to any cause
• Area under the concentration-time curve (AUC) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  Pharmacokinetic (PK) endpoint
• Concentration at the end of infusion (Ceoi) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  PK endpoint
• Maximum observed concentration (Cmax) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  PK endpoint
• Time to maximum observed concentration (Tmax) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  PK endpoint
• Trough concentration (Ctrough) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  PK endpoint
• Apparent terminal elimination half-life (t1/2) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]
  PK endpoint
• Number of participants with antidrug antibodies (ADAs) [ Time Frame: Through 30-37 days following last dose of sigvotatug vedotin; up to 3 years ]

Original Secondary Outcome Measures (submitted: May 12, 2020)

• Area under the concentration-time curve (AUC) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  Pharmacokinetic (PK) endpoint
• Concentration at the end of infusion (Ceoi) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  PK endpoint
• Maximum concentration (Cmax) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  PK endpoint
• Time to maximum concentration (Tmax) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  PK endpoint
• Trough concentration (Ctrough) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  PK endpoint
• Apparent terminal elimination half-life (t1/2) [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
  PK endpoint
• Number of participants with antidrug antibodies [ Time Frame: Through 30-37 days following last dose of SGN-B6A; up to 2 years ]
• Objective response rate (ORR) per RECIST v1.1 [ Time Frame: Up to approximately 3 years ]
  The proportion of participants with complete response (CR) or partial response (PR)
• Duration of objective response (DOR) [ Time Frame: Up to approximately 3 years ]
  The time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression or to death due to any cause
• Progression-free survival (PFS) [ Time Frame: Up to approximately 3 years ]
  The time from first response to the first documentation of disease progression, or death due to any cause
• Overall survival (OS) [ Time Frame: Up to approximately 3 years ]
  The time from start of study treatment to the date of death due to any cause

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of SGN-B6A in Advanced Solid Tumors
• Official Title: A Phase 1 Study of SGN-B6A in Advanced Solid Tumors

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Drug: sigvotatug vedotin
  Administered into the vein (IV; intravenously)
  Other Name: SGN-B6A
• Drug: pembrolizumab
  200mg every 3 weeks or 400mg every 6 weeks, given by IV
  Other Name: 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

Study Arms

• Experimental: Part A: Dose escalation
  sigvotatug vedotin monotherapy
  Intervention: Drug: sigvotatug vedotin
• Experimental: Part B: Dose expansion
  sigvotatug vedotin monotherapy
  Intervention: Drug: sigvotatug vedotin
• Experimental: Part C: sigvotatug vedotin combination therapy in NSCLC, HNSCC, ESCC
  sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
  Interventions:

  • Drug: sigvotatug vedotin
  • Drug: pembrolizumab
  • Drug: cisplatin
  • Drug: carboplatin
• Experimental: Part D: sigvotatug vedotin combination therapy in 1L NSCLC
  sigvotatug vedotin + pembrolizumab +/- (carboplatin)
  Interventions:

  • Drug: sigvotatug vedotin
  • Drug: pembrolizumab
  • Drug: carboplatin
• Experimental: Part D: sigvotatug vedotin combination therapy in 1L HNSCC
  sigvotatug vedotin + pembrolizumab +/- (carboplatin or cisplatin)
  Interventions:

  • Drug: sigvotatug vedotin
  • Drug: pembrolizumab
  • Drug: cisplatin
  • Drug: carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2024): 824
• Original Estimated Enrollment (submitted: May 12, 2020): 235
• Estimated Study Completion Date: October 31, 2028
• Estimated Primary Completion Date: November 30, 2026 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Seagen Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

• Listed Location Countries: France, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT04389632
• Other Study ID Numbers: SGNB6A-001; 2023-508469-34 ( Other Identifier: Registry Identifier: CTIS (EU) )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: May 2024