A Safety Study of SGN-TGT in Patients With Advanced Cancer

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

Study Description

Brief Summary:

This trial will look at a drug called SGN-TGT to find out whether it is safe for patients with solid tumors and lymphomas. It will study SGN-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 SGN-TGT works to treat solid tumors and lymphomas.

The study will have three groups or "parts." Part A of the study will find out how much SGN-TGT should be given to patients. Part B will use the dose found in Part A to find out how safe SGN-TGT is and if it works to treat solid tumors and lymphomas. Part C will study how well SGN-TGT with the PD-1 inhibitor pembrolizumab works to treat solid tumors and lymphomas. PD-1 inhibitors are drugs that can be used to treat these types of cancer.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer; Gastric Carcinoma; Classical Hodgkin Lymphoma; Diffuse Large B-cell Lymphoma; Peripheral T-cell Lymphoma	Drug: SGN-TGT; Drug: pembrolizumab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 111 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of SGN-TGT in Subjects With Advanced Malignancies
• Estimated Study Start Date: May 31, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: January 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monotherapy (Parts A and B)	Drug: SGN-TGT; Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle
Experimental: Combination Therapy (Part C)	Drug: SGN-TGT; Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle; 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 reporting 1 or more TEAE [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
2. Number of participants with Grade 3 or higher adverse events (AEs) [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
3. Number of participants with 1 or more serious AE [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
4. Number of participants with 1 or more treatment-related AE [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
5. Number of participants with laboratory abnormalities by grade [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
6. Number of participants with a DLT at each dose level [ Time Frame: Up to 28 days ]

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. Best response rate [ Time Frame: Up to approximately 3 years ]
   Proportion of participants with CR, PR, or stable disease (SD) 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 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
8. Time to maximum concentration (Tmax) [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
9. Maximum concentration (Cmax) [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
10. Trough concentration (Ctrough) [ Time Frame: Through 30-37 days following last dose of SGN-TGT; up to approximately 3 years ]
11. Number of participants with antidrug antibodies (ADA) [ Time Frame: Through 30-37 days following last dose of SGN-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 or gastric carcinoma

    • Lymphoma, including:

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

  • Relapsed, refractory or progressive disease, specifically:

    • Solid tumors: Following at least 1 prior systemic therapy and for which no further standard therapy is available at the time of enrollment, and with the specific prior therapies as listed below.

      • NSCLC: Participants must have received platinum-based therapy. Participants must have received at least 1 PD-1- or PD-L1-targeted therapy, unless clinically contraindicated. Participants must have received mutation-targeted therapies as appropriate. These agents may have been administered either as single agents or in combination.
      • Gastric Carcinoma: Participants must have received prior platinum and fluoropyrimidine-based chemotherapy, unless clinically contraindicated. If appropriate, participants must also have received ramucirumab. In addition, participants should have received HER2/neu-targeted therapy if appropriate. Participants with PD-L1 expressing tumors (CPS scores of 1 or greater) must have received appropriate anti-PD-1 or anti-PD-L1 therapy unless clinically contraindicated.

    • 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 SGN-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 SGN-TGT
• Pervious 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 SGN-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 SGN-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: Seattle Genetics Trial Information Support; 866-333-7436; clinicaltrials@seagen.com

Locations

United States, Oregon

Providence Portland Medical Center; Recruiting

Portland, Oregon, United States, 97213

Contact: Lynn Freitas 503-215-6054 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

Sponsors and Collaborators

Seattle Genetics, Inc.

Investigators

• Study Director: Phillip Garfin, MD, PhD; Seattle Genetics, Inc.

More Information

• Responsible Party: Seattle Genetics, Inc.
• ClinicalTrials.gov Identifier: NCT04254107
• Other Study ID Numbers: SGNTGT-001
• First Posted: February 5, 2020
• Last Update Posted: June 2, 2020
• Last Verified: May 31, 2020

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

Keywords provided by Seattle Genetics, Inc.:

NSCLC; cHL; DLBCL; PTCL-NOS

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, T-Cell, Peripheral; Stomach Neoplasms; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents