Clinical Trials /

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

NCT04254107

Description:

This trial will look at a drug called SGN-TGT (also known as SEA-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.

Related Conditions:
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Gastric Carcinoma
  • Lymphoma
  • Non-Small Cell Lung Carcinoma
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Safety Study of SGN-TGT (SEA-TGT) in Patients With Advanced Cancer
  • Official Title: A Phase 1 Study of SGN-TGT in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: SGNTGT-001
  • NCT ID: NCT04254107

Conditions

  • Non-small Cell Lung Cancer
  • Gastric Carcinoma
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-cell Lymphoma
  • Peripheral T-cell Lymphoma

Interventions

DrugSynonymsArms
SGN-TGTSEA-TGTCombination Therapy (Part C)
pembrolizumabCombination Therapy (Part C)

Purpose

This trial will look at a drug called SGN-TGT (also known as SEA-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.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy (Parts A and B)Experimental
  • SGN-TGT
Combination Therapy (Part C)Experimental
  • SGN-TGT
  • pembrolizumab

Eligibility 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 (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 SGN-TGT
             (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 SGN-TGT (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 SGN-TGT
             (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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants reporting 1 or more TEAE
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Proportion of participants with complete response (CR) and partial response (PR) per the participant's specific tumor response criteria
Measure:Best response rate
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Proportion of participants with CR, PR, or stable disease (SD) per the participant's specific tumor response criteria
Measure:Duration of objective response
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from first response to the first documentation of disease progression or death due to any cause
Measure:Duration of CR
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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
Measure:Duration of progression-free survival
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from first dose to the first documentation of disease progression or death due to any cause
Measure:Duration of overall survival
Time Frame:Up to approximately 3 years
Safety Issue:
Description:Time from start of study treatment to the date of death due to any cause
Measure:Area under the concentration-time curve (AUC)
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:
Measure:Time to maximum concentration (Tmax)
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:
Measure:Maximum concentration (Cmax)
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:
Measure:Trough concentration (Ctrough)
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:
Measure:Number of participants with antidrug antibodies (ADA)
Time Frame:Through 30-37 days following last dose of study drug; up to approximately 3 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Trial Keywords

  • NSCLC
  • cHL
  • DLBCL
  • PTCL-NOS

Last Updated

July 7, 2020