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

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with adverse events (AEs)

Primary Outcome 1 - Timeframe: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years

Primary Outcome 2 - Measure: Number of participants with laboratory abnormalities by grade

Primary Outcome 2 - Timeframe: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years

Primary Outcome 3 - Measure: Number of participants with a dose-limiting toxicity (DLT) at each dose level

Primary Outcome 3 - Timeframe: Up to 21 days

CONDITION

• 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
• Cervical Cancer

ELIGIBILITY

Monotherapy Inclusion Criteria (Parts A and B)
* Histologically- or cytologically-confirmed advanced or metastatic malignancy, defined as:
* One of the following tumor types:
* Unresectable locally-advanced or metastatic non-small cell lung cancer (NSCLC), gastric/gastroesophageal (GE) junction carcinoma, cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC), bladder cancer, cervical cancer, ovarian cancer, or triple negative breast cancer (TNBC)

- * Lymphomas, including:
* 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 (less than or equal to [≤] 12 months from screening). If archived tissue is not available, a fresh baseline 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)
* ECOG Performance Status score of 0 or 1

- * NSCLC: histological or cytological confirmed metastatic disease. Participants must have received no prior anti-PD-1/PD-L1 therapy allowed.

- * HNSCC: histological or cytological confirmed metastatic disease. Participants must have received no prior exposure to anti-PD-1/PD-L1 therapy.

- * Cutaneous Melanoma: histological or cytological confirmed metastatic disease. Participants must not have received anti-PD-1/PD-L1 targeted therapy.

- * Measurable disease by CT or magnetic resonance imaging (MRI) as defined by RECIST V1.1

- * Participants must provide archival tumor tissue from the most recent biopsy (≤12 months from screening). If archival tissue is not available, a fresh baseline tumor biopsy that has not been previously irradiated is required for any participant whose tumors are considered accessible and appropriate in the opinion of the investigator.
Combination Inclusion Criteria (Part D)
* Histologically- or cytologically-confirmed advanced stage cHL

- * cHL patients that have failed standard of care for R/R disease including prior treatment with BV.

- * FDG PET emission tomography avid and bidimensional measurable disease of at least 1.5 cm in longest axis as documented by radiographic technique

- * ECOG performance status of ≤ 2

- * Participants are required to have tumor tissue, if available, from the most recent biopsy (≤12 months from screening) prior to start of study treatment. If archival tissue is not available, a fresh screening tumor biopsy is required for any participant whose tumors are considered accessible and appropriate in the opinion of the investigator.
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 (ADC), 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.

- * Previous allogeneic stem cell transplant (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 (greater than [>]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.

- * Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT
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.

- * Active, non-infectious pneumonitis, pulmonary fibrosis, or known history of immune mediated pneumonitis.

- * 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, ADC, 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 or sasanlimab

- * 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.

- * 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
Combination Exclusion Criteria (Part D)
* 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 CNS disease): ≤7 days prior to start of SEA-TGT

- * Immune-checkpoint inhibitors: 4 weeks

- * Monoclonal antibodies, ADC (except brentuximab vedotin), or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)

- * T-cell or other cell-based therapies: 12 weeks

- * Known active CNS involvement by lymphoma

- * 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Andres Forero-Torres, MD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Andres Forero-Torres, MD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION