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

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04254107

Collaborator

(none)

397

Enrollment

Locations

Arms

Anticipated Duration (Months)

13.2

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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 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 sasanlimab works to treat solid tumors.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: SEA-TGT Drug: sasanlimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

397 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of SEA-TGT (SGN-TGT) in Subjects With Advanced Malignancies

Actual Study Start Date :

May 29, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Monotherapy (Parts A and B) SEA-TGT	Drug: SEA-TGT Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle Other Names: SGN-TGT
Experimental: Combination Therapy (Part C) SEA-TGT + sasanlimab	Drug: SEA-TGT Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle Other Names: SGN-TGT Drug: sasanlimab Given via injection under the skin (subcutaneous) on Day 1 of each 21-day cycle

Arm

Intervention/Treatment

Experimental: Monotherapy (Parts A and B)

SEA-TGT

Drug: SEA-TGT

Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle

Other Names:

SGN-TGT

Experimental: Combination Therapy (Part C)

SEA-TGT + sasanlimab

Drug: SEA-TGT

Given into the vein (IV; intravenously) on Day 1 of each 21-day cycle

Other Names:

SGN-TGT

Drug: sasanlimab

Given via injection under the skin (subcutaneous) on Day 1 of each 21-day cycle

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Number of participants with laboratory abnormalities by grade [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics
Number of participants with a DLT at each dose level [Up to 21 days]
To be summarized using descriptive statistics

Secondary Outcome Measures

Objective Response Rate (ORR) [Up to approximately 3 years]
Proportion of participants with complete response (CR) and partial response (PR) per the participant's specific tumor response criteria
Complete response (CR) rate [Up to approximately 3 years]
Proportion of participants with CR per the participant's specific tumor response criteria
Duration of objective response [Up to approximately 3 years]
Time from first response to the first documentation of disease progression or death due to any cause
Duration of CR [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
Duration of progression-free survival [Up to approximately 3 years]
Time from first dose to the first documentation of disease progression or death due to any cause
Duration of overall survival [Up to approximately 3 years]
Time from start of study treatment to the date of death due to any cause
Area under the concentration-time curve (AUC) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics.
Time to maximum concentration (tmax) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics.
Maximum concentration (Cmax) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics.
Trough concentration (Ctrough) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics.
Number of participants with antidrug antibodies (ADA) [Through 45-52 days following last dose of SEA-TGT; up to approximately 3 years]
To be summarized using descriptive statistics.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:
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 (≤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 archived tumor tissue, if available, from the most recent biopsy (≤12 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.

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.
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.
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, 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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35249
2	Arizona Oncology Associates, PC - HOPE	Tucson	Arizona	United States	85710
3	City of Hope National Medical Center	Duarte	California	United States	91010-3000
4	University of California at San Francisco	San Francisco	California	United States	94134
5	Yale Cancer Center	New Haven	Connecticut	United States	06520
6	Johns Hopkins Medical Center	Baltimore	Maryland	United States	21287
7	Maryland Oncology Hematology, P.A.	Rockville	Maryland	United States	20850
8	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
9	Minnesota Oncology Hematology P.A.	Minneapolis	Minnesota	United States	55404
10	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
11	Weill Cornell Medicine	New York	New York	United States	10021
12	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina	United States	27157
13	University of Cincinnati Cancer Institute	Cincinnati	Ohio	United States	45219
14	Providence Portland Medical Center	Portland	Oregon	United States	97213
15	University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37204
17	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
18	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas	United States	75246
19	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030
20	Texas Oncology - Tyler	Tyler	Texas	United States	75702
21	Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care	Blacksburg	Virginia	United States	24060
22	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
23	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin	United States	53792
24	University Health Network, Princess Margaret Hospital	Toronto	Other	Canada	M5G 2C1
25	Institut Gustave Roussy	Villejuif Cedex	Other	France	94805
26	Istituto Europeo di Oncologia	Milano	Other	Italy	20141
27	Hospital Universitario Vall d'Hebron	Barcelona	Other	Spain	08035
28	HM Centro Integral Oncologico Clara Campal	Madrid	Other	Spain	28050
29	Sarah Cannon Research Institute UK	London	Other	United Kingdom	W1G 6AD
30	The Royal Marsden Hospital (Surrey)	Sutton	Other	United Kingdom	SM2 5PT