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