A Safety Study of SGN-35T in Adults With Advanced Cancers

Study Overview
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Brief Summary
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This clinical trial is studying lymphoma. Lymphoma is a cancer that starts in the blood cells that fight infections. There are several types of lymphoma. This study will enroll people who have lymphoma, such as classical Hodgkin lymphoma, peripheral T-cell lymphoma including systemic anaplastic large cell lymphoma, diffuse large B-cell lymphoma, or types of primary cutaneous lymphoma. This clinical trial uses a drug called SGN-35T. The study drug is in testing and has not been approved for sale. This is the first time SGN-35T will be used in people. The study drug will be given as an infusion through a vein. This study will test the safety of SGN-35T in participants with lymphoma. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. This study will have three parts. Parts A and B of the study will find out the best dose and dosing schedule for SGN-35T. Part C will use the dose found in parts A and B to find out how safe SGN-35T is and if it works to treat select lymphomas.

Detailed Description
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This is a phase 1, open-label, multicenter study designed to characterize the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of SGN-35T in adults with select relapsed/refractory lymphomas. SGN-35T is a CD30-directed antibody-drug conjugate and will be studied in patients with lymphomas expressing CD30.

Official Title
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An Open-label Phase 1 Study to Evaluate the Safety of SGN-35T in Adults With Advanced Malignancies

Conditions
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Lymphoma, T-Cell, Cutaneous, Hodgkin Disease, Lymphoma, T-Cell, Peripheral, Lymphoma, Large-Cell, Anaplastic, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: SGN-35T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Disease indication For dose escalation and dose optimization (Part A and Part B): Participants with a histologically confirmed lymphoid neoplasm (including relapsed/refractory [R/R] classical Hodgkin lymphoma [cHL], R/R peripheral T-cell lymphoma [PTCL], R/R systemic anaplastic large cell lymphoma [sALCL] , R/R mature B-cell neoplasms, and select R/R primary cutaneous lymphomas [PCLs]) who in the judgment of the investigator have no appropriate standard therapy available at the time of enrollment and are a candidate for SGN-35T treatment. Participants must have a detectable CD30 expression level (≥1%) in tumor tissue (except cHL and ALCL where CD30 is universally expressed). For dose expansion (Part C) Participants are eligible irrespective of CD30 expression on tumor tissue. Participants with cHL: Participants with R/R cHL who have received at least 3 prior systemic therapies (autologous stem cell transplant [ASCT] and the associated high dose chemotherapy prior to ASCT are considered to be 1 prior line) and meet all of the following additional criteria: Participants who have not received ASCT must have refused or been deemed ineligible. Participants must have received or been ineligible to receive an anti-PD-1 agent. Participants with PTCL: Participants with R/R PTCL (excluding R/R sALCL) who have received at least 2 prior systemic therapies or received at least 1 prior systemic therapy and there is no other available treatment that is considered appropriate by the investigator. Participants with R/R sALCL must have ALK status documented and must meet one of the following criteria: Disease recurrence or progression following at least 2 prior systemic therapies where 1 regimen included brentuximab vedotin, or Disease recurrence or progression following only 1 prior line of therapy which included brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone An Eastern Cooperative Oncology Group (ECOG) Performance Status score ≤1. Fluorodeoxyglucose positron emission tomography (FDG PET) avid and bidimensional measurable disease as documented by radiographic technique (spiral CT preferred) per Lugano criteria at baseline (Cheson 2014) (not applicable for subjects with PCL). Exclusion Criteria: Previous exposure to CD30 targeted therapy (exception: participants with cHL, PTCL, or PCL may have received prior brentuximab vedotin but no more than 2 prior brentuximab vedotin based lines of therapy and at least 3 months should have elapsed before enrollment). History of another malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death. Active cerebral/meningeal disease related to the underlying malignancy. Received previous ASCT infusion <12 weeks prior to first SGN-35T dose. Participants with previous allogeneic stem cell transplant (SCT) if they meet any of the following criteria: <100 days from allogeneic SCT. Participants ≥100 days from allogeneic SCT who are stable without immunosuppressive therapy for at least 12 weeks are permitted. Active acute or chronic graft versus host disease or receiving immunosuppressive therapy as treatment for or prophylaxis against graft versus host disease. Cytomegalovirus (CMV) PCR ≥500 IU/mL, OR rising DNA levels >5-times baseline within 1 month, OR detectable CMV PCR receiving pre-emptive therapy; prior PCR positivity that was successfully treated is acceptable provided the baseline PCR result is negative prior to the first dose of study drug. Grade 2 or higher pulmonary disease unrelated to underlying malignancy, or history of Grade 2 or higher drug-induced interstitial lung disease (ILD) or immune checkpoint inhibitor (ICI)-related ILD. Clinically significant lung disease requiring systemic corticosteroid treatment within 6 months prior to enrollment or who are suspected to have such diseases via radiographic imaging and/or functional tests conducted during the screening period.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-35T<br>SGN-35T monotherapy | Drug: SGN-35T<br>* Given into the vein (IV; intravenously)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention | Through 30-37 days after last study treatment, approximately 1 year | 
| Number of participants with laboratory abnormalities |  | Through 30-37 days after last study treatment, approximately 1 year | 
| Number of participants with dose modifications due to AEs |  | Up to approximately 1 year | 
| Number of participants with dose-limiting toxicities (DLTs) |  | Up to 21 days | 
| Number of participants with DLTs by dose level |  | Up to 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) parameter - Area under the concentration-time curve (AUC) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, approximately 1 year | 
| PK parameter - Maximum concentration (Cmax) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, approximately 1 year | 
| PK parameter - Time to Cmax (Tmax) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, approximately 1 year | 
| Number of participants with antidrug antibodies (ADA) | To be summarized using descriptive statistics | Through 30-37 days after last study treatment, approximately 1 year | 
| Objective response rate (ORR) as assessed by the investigator | A subject is determined to have an objective response if, based on disease-specific assessment criteria, they achieve a complete response (CR) or partial response (PR) as assessed by the investigator. The ORR is defined as the percentage of participants with an objective response. | Up to approximately 1 year | 
| Complete response (CR) rate as assessed by the investigator | CR rate is defined as the percentage of subjects with CR. | Up to approximately 1 year | 
| Duration of response (DOR) | DOR is defined as the time from the start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per disease-specific assessment criteria as assessed by the investigator or to death due to any cause, whichever comes first. | Up to approximately 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cHL, ALCL, PCL, PTCL, DLBCL, CTCL, Non-Hodgkin Lymphoma, Seattle Genetics