A Safety Study of SEA-TGT (SGN-TGT) in Advanced Cancer

• ClinicalTrials.gov Identifier: NCT04254107
• Recruitment Status: Recruiting
• First Posted: February 5, 2020
• Last Update Posted: February 2, 2021
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Study Description

Brief Summary:

This trial will look at a drug called SEA-TGT (also known as SGN-TGT) to find out whether it is safe for patients with solid tumors and lymphomas. It will study SEA-TGT to find out what its side effects are. A side effect is anything the drug does besides treating cancer. It will also study whether SEA-TGT works to treat solid tumors and lymphomas.

The study will have three parts. Part A of the study will find out how much SEA-TGT should be given to patients. Part B will use the dose found in Part A to find out how safe SEA-TGT is and if it works to treat solid tumors and lymphomas. Part C will study how well SEA-TGT with pembrolizumab works to treat solid tumors. Pembrolizumab is a drug that can be used to treat these types of cancer.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer; Gastric Carcinoma; Gastroesophageal Junction Carcinoma; Classical Hodgkin Lymphoma; Diffuse Large B-cell Lymphoma; Peripheral T-cell Lymphoma; Cutaneous Melanoma; Head and Neck Squamous Cell Carcinoma; Bladder Cancer; Ovarian Cancer; Triple Negative Breast Cancer	Drug: SEA-TGT; Drug: pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 231 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of SEA-TGT (SGN-TGT) in Subjects With Advanced Malignancies
• Actual Study Start Date: May 29, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: March 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monotherapy (Parts A and B)	Drug: SEA-TGT; Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle; Other Name: SGN-TGT
Experimental: Combination Therapy (Part C)	Drug: SEA-TGT; Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle; Other Name: SGN-TGT; Drug: pembrolizumab; Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
   To be summarized using descriptive statistics
2. Number of participants with laboratory abnormalities by grade [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
   To be summarized using descriptive statistics
3. Number of participants with a DLT at each dose level [ Time Frame: Up to 21 days ]
   To be summarized using descriptive statistics

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: Up to approximately 3 years ]
   Proportion of participants with complete response (CR) and partial response (PR) per the participant's specific tumor response criteria
2. Complete response (CR) rate [ Time Frame: Up to approximately 3 years ]
   Proportion of participants with CR per the participant's specific tumor response criteria
3. Duration of objective response [ Time Frame: Up to approximately 3 years ]
   Time from first response to the first documentation of disease progression or death due to any cause
4. Duration of CR [ Time Frame: Up to approximately 3 years ]
   Time from start of the first documentation of CR to the first documentation of confirmed tumor progression or to death due to any cause, whichever comes first
5. Duration of progression-free survival [ Time Frame: Up to approximately 3 years ]
   Time from first dose to the first documentation of disease progression or death due to any cause
6. Duration of overall survival [ Time Frame: Up to approximately 3 years ]
   Time from start of study treatment to the date of death due to any cause
7. Area under the concentration-time curve (AUC) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
8. Time to maximum concentration (Tmax) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
9. Maximum concentration (Cmax) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
10. Trough concentration (Ctrough) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]
11. Number of participants with antidrug antibodies (ADA) [ Time Frame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Monotherapy Inclusion Criteria (Parts A and B)

• Histologically- or cytologically-confirmed advanced or metastatic malignancy, defined as:

  • One of the following disease indications:

    • Unresectable locally-advanced or metastatic NSCLC, gastric/gastroesophageal (GE) junction carcinoma, cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC), bladder cancer, ovarian cancer, or triple negative breast cancer (TNBC)

    • Lymphoma, including:

      • Classical Hodgkin lymphoma (cHL)
      • Diffuse large B-cell lymphoma (DLBCL)
      • Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)

    • Lymphoma: Participants should have disease progression on or after treatment with standard therapies expected to provide benefit in the judgement of the investigator.

      • cHL: Participants must have received at least 3 prior systemic therapies. Participants should have had disease recurrence or progression following brentuximab vedotin therapy or have been ineligible to receive brentuximab vedotin. Participants who have not received autologous stem cell transplant (SCT) must have refused or been deemed ineligible. Participants should have received or not be eligible to have received an anti-PD-1 agent.
      • DLBCL: Participants must have received at least 2 prior systemic chemo-immunotherapy regimens, including an anti-CD20 agent and combination chemotherapy. Unless clinically contraindicated, participants should have had disease that has relapsed after or be refractory to intensive salvage chemotherapy, including autologous SCT.
      • PTCL-NOS: Participants must have had at least 1 prior systemic therapy. Participants must have received or have been ineligible to receive the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy. Participants with CD30-positive disease must have received or be ineligible to receive brentuximab vedotin. Participants must have also received intensive salvage therapy (defined as combination chemotherapy ± autologous SCT) unless they refused or were deemed ineligible.

• Measurable disease defined as:

  • Solid tumors: Measurable disease according to RECIST V1.1
  • Lymphomas: Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and measurable disease of ≥15 mm in the greatest transverse diameter by computed tomography (CT) scan, as assessed by the site radiologist.
• A representative archival tumor tissue sample should be available as follows: Participants must provide archived tumor tissue, if available, from the most recent biopsy (≤24 months from screening). If archived tissue is not available, a fresh screening tumor biopsy will be requested for any participant enrolled in Part B whose tumors are considered accessible and appropriate in the opinion of the investigator.
• ECOG Performance Status score of 0 or 1

Combination Inclusion Criteria (Part C)

• Participants with a histologically-confirmed advanced NSCLC or gastric carcinoma meeting at least 1 of the following criteria:

  • Unresectable locally-advanced or metastatic
  • Relapsed, refractory, or progressive disease following at least 1 prior systemic therapy
• Measurable disease by CT or magnetic resonance imaging (MRI) as defined by RECIST V1.1
• A representative tumor tissue sample should be available as follows: Participants must provide archived tumor tissue, if available, from the most recent biopsy (≤24 months from screening). If archived tissue is not available, a fresh screening tumor biopsy will be requested for any participant whose tumors are considered accessible and appropriate in the opinion of the investigator.
• ECOG Performance Status score of 0 or 1

Monotherapy Exclusion Criteria (Parts A and B)

• History of another malignancy within 2 years before the 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.

• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not been completed before the first dose of study drug within the timeframe as follows:

  • Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks

    • Palliative radiotherapy (≤2 weeks of radiotherapy to non-central nervous system [CNS] disease): ≤7 days prior to start of SEA-TGT
  • Immune-checkpoint inhibitors: 4 weeks
  • Monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
  • T-cell or other cell-based therapies: 12 weeks

• Known CNS metastases

  • Participants with a history of CNS metastases are allowed if they have undergone treatment for the CNS disease, symptoms have resolved, and steroids have been discontinued.
  • Leptomeningeal involvement by malignant disease is excluded regardless of prior treatment.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT
• Previous allogeneic SCT. Participants with prior autologous SCT may be eligible if they are >100 days from autologous SCT and fulfill all other inclusion criteria.
• Prior use of any anti-TIGIT mAb.
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the absence of active immune disease.

Combination Exclusion Criteria (Part C)

• History of another malignancy within 2 years before the 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.
• Previous therapy with an anti-PD-1 or anti-PD-L1 inhibitor.

• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not been completed before the first dose of study drug within the timeframe as follows:

  • Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks

    • Palliative radiotherapy (≤2 weeks of radiotherapy to non-CNS disease): ≤7 days prior to start of SEA-TGT.
  • Immune-checkpoint inhibitors: 4 weeks
  • Monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
  • T-cell or other cell-based therapies: 12 weeks

• Known active CNS metastases.

  • Participants with a history of CNS metastases are allowed if they have undergone treatment for the CNS disease, symptoms have resolved, and steroids have been discontinued.
  • Leptomeningeal involvement by malignant disease is excluded regardless of prior treatment.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT
• Participants with active known or suspected autoimmune disease or significant autoimmune-related toxicity from prior immuno-oncology-based therapy (prior autoimmune colitis, pneumonitis, transaminitis); Participants with vitiligo, controlled type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• Uncontrolled diabetes mellitus
• History of interstitial lung disease
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the absence of active immune disease.
• Prior use of any anti-TIGIT mAb

Contacts and Locations

Contacts

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

Locations

United States, Alabama

University of Alabama at Birmingham; Recruiting

Birmingham, Alabama, United States, 35249

Contact: Jenny King jpking@uabmc.edu

Principal Investigator: Amitkumar Mehta

United States, California

City of Hope National Medical Center; Recruiting

Duarte, California, United States, 91010-3000

Principal Investigator: Jasmine Zain

United States, Minnesota

Mayo Clinic Rochester; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Ashley Moyer 507-284-0923 Haeska.Ashley@mayo.edu

Principal Investigator: Stephen Ansell

United States, Oregon

Providence Portland Medical Center; Recruiting

Portland, Oregon, United States, 97213

Contact: Lynn Freitas lynn.freitas@providence.org

Contact: Christina Lopez 503-215-5696 canrsrchstudies@providence.org

Principal Investigator: Rachel Sanborn

United States, Pennsylvania

Hillman Cancer Center / University of Pittsburgh Medical Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contact: Barbara Stadterman 412-647-2811 stadtermanbm@upmc.edu

Contact: Catherine Davis 412-647-2811 davisc20@upmc.edu

Principal Investigator: Diwakar Davar

France

Institut Gustave Roussy; Recruiting

Villejuif, France, 94805

Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Principal Investigator: Vincent Vibrag

Italy

Istituto Europeo di Oncologia; Recruiting

Milan, Italy, 20141

Spain

Hospital Universitario Vall d'Hebron; Recruiting

Barcelona, Spain, 08035

Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

United Kingdom

The Royal Marsden Hospital (Surrey); Recruiting

Sutton, United Kingdom, SM2 5PT

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

Principal Investigator: Anna Minchom

Sponsors and Collaborators

Seagen Inc.

Investigators

• Study Director: Andres Forero-Torres, MD; Seagen Inc.

More Information

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT04254107
• Other Study ID Numbers: SGNTGT-001
• First Posted: February 5, 2020
• Last Update Posted: February 2, 2021
• Last Verified: January 2021

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

Keywords provided by Seagen Inc.:

NSCLC; cHL; HNSCC; TNBC; DLBCL; PTCL-NOS; Seattle Genetics

Additional relevant MeSH terms:

Lymphoma; Carcinoma; Lymphoma, Large B-Cell, Diffuse; Triple Negative Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Lymphoma, T-Cell, Peripheral; Stomach Neoplasms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Site; Carcinoma, Squamous Cell; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Breast Neoplasms; Breast Diseases; Skin Diseases; Head and Neck Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pembrolizumab; Antineoplastic Agents, Immunological