Clinical trial NCT04254107: A Safety Study of SEA-TGT (SGN-TGT) in Advanced Cancer
Official title: A Phase 1 Study of SEA-TGT (SGN-TGT) in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Keywords: NSCLC
cHL
HNSCC
TNBC
DLBCL
PTCL-NOS
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-05
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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 four 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 sasanlimab works to treat solid tumors. Part D will study how well SEA-TGT with brentuximab vedotin works to treat classical Hodgkin lymphoma (cHL).


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Number of participants with laboratory abnormalities by grade
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Number of participants with a dose-limiting toxicity (DLT) at each dose level
timeFrame: Up to 21 days
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
measure: Complete response (CR) rate
timeFrame: Up to approximately 3 years
measure: Duration of objective response
timeFrame: Up to approximately 3 years
measure: Duration of CR
timeFrame: Up to approximately 3 years
measure: Duration of progression-free survival
timeFrame: Up to approximately 3 years
measure: Duration of overall survival
timeFrame: Up to approximately 3 years
measure: Area under the concentration-time curve (AUC)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Time to maximum concentration (tmax)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Maximum concentration (Cmax)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Trough concentration (Ctrough)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
measure: Number of participants with antidrug antibodies (ADA)
timeFrame: Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco | HDFCCC - Hematopoietic Malignancies
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology P.A.
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Blacksburg
country: United States
facility: Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: University of Alberta / Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Hospital
state: Other
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Rome
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: L'Institut Catala d'Oncologia
state: Other
city: Madrid
country: Spain
facility: HM Centro Integral Oncologico Clara Campal
state: Other
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
state: Other
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital (Surrey)
state: Other
Study officials:
affiliation: Seagen Inc.
name: Andres Forero-Torres, MD
role: STUDY_DIRECTOR
References: