A Safety Study of SGN-2FF for Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is being done to find out the side effects (unwanted effects) that are caused in patients with cancers who are given SGN-2FF. This study will also attempt to find the most suitable dose in the disease or condition being studied and look at other effects of SGN2FF, including its effect on cancer. This study has several different parts. Part A will try to find the highest safe dose. Part B will enroll more patients to be treated at the highest safe dose or a lower dose to better understand how well SGN-2FF is tolerated. Part C will try to find the highest safe dose of SGN-2FF when it is given combined with pembrolizumab. Pembrolizumab is a standard treatment for cancer. Part D will enroll more patients to be treated at the highest safe dose of SGN-2FF combined with pembrolizumab or a lower dose of SGN-2FF to better understand how well SGN-2FF is tolerated when it is given with pembrolizumab.

Detailed Description
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This is a phase 1, open-label, multicenter, dose escalation study that will examine the safety profile of SGN-2FF given orally to patients with advanced solid tumors. The primary goal of the study is to identify the maximum tolerated dose (MTD), or optimal biological dose (OBD) that does not exceed the MTD. The pharmacokinetics (PK) and antitumor activity of SGN-2FF will also be evaluated. In this study, SGN-2FF will be evaluated as monotherapy and as combination therapy with the standard approved dose of pembrolizumab. The monotherapy portion of the study will be conducted in 2 sequential parts (Part A and Part B). Part A will enroll patients for dose escalation to estimate the MTD /OBD and help determine the dosing regimen that will be tested in Part B. The OBD will be evaluated by assessing the activity of SGN-2FF, including pharmacodynamics, PK, and other observations in dose escalation. Part B will explore the recommended dose/regimen in up to 3 focused expansion cohorts. The combination therapy portion of the study will be conducted in 2 sequential parts (Part C and Part D). SGN-2FF will be administered orally according to the dose and schedule assigned, with a lead-in period of 2 weeks prior to pembrolizumab administration. The lead-in period may be discontinued based on emerging nonclinical and/or clinical data. Part C will enroll patients for dose escalation to estimate the MTD /OBD and the dosing regimen that will be tested in Part D. Part D will explore the recommended dose/regimen in up to 3 focused expansion cohorts. Safety will be monitored throughout the trial by the safety monitoring committee which will meet frequently to review the emerging safety data and make dose-escalation and dosing-interval recommendations. Antitumor activity will be assessed by radiographic imaging. Patients may continue treatment until progression of their disease or intolerable side effects. Retreatment with SGN-2FF monotherapy or with SGN-2FF and pembrolizumab combination therapy is permitted with medical monitor approval for patients who achieve stable disease, a complete response, or partial response on study and then experience disease progression after discontinuing prior treatment with SGN 2FF.

Official Title
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A Phase 1, Multicenter, Open-label, Dose-escalation Study of SGN-2FF in Patients With Advanced Solid Tumors

Conditions
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Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Breast Neoplasms, Urinary Bladder Neoplasm, Carcinoma, Squamous Cell of Head and Neck, Colorectal Neoplasms, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma

Intervention / Treatment
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* Drug: SGN-2FF
* Drug: pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically-confirmed, locally advanced, or metastatic solid malignancy that is relapsed, refractory, or progressing following at least 1 prior systemic therapy (Part A) Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as defined by RECIST 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 1 Patients in Part B must have histologically or cytologically-confirmed, locally-advanced, or metastatic solid malignancy within the disease indications of Part A Adequate baseline hematologic, renal, and hepatic function Patients for whom there is no further standard therapy available at the time of enrollment (Part A) Patients with a histologically-confirmed, advanced solid malignancy meeting one of the following criteria: (1) indication for which pembrolizumab is approved or (2) relapsed, refractory, or progressive disease following at least 1 prior therapy and for which no further standard therapy is a available (Parts C and D) Exclusion Criteria: Patients with carcinomatous meningitis or active central nervous system (CNS) metastases Patients with recent (within 14 days) or serious ongoing infection Patients requiring systemic treatment with corticosteroids (greater than 10 mg prednisone equivalents) or immunosuppressive medications within 14 days of enrollment Patients with active known or suspected autoimmune disease or significant autoimmune-related toxicity from prior immuno-oncology therapy Known active or latent tuberculosis Uncontrolled diabetes mellitus History of interstitial lung disease Gastrointestinal abnormality that would affect absorption of SGN-2FF Patients tested positive for hepatitis B or with a known, active hepatitis C infection Women who are pregnant or breastfeeding Patients with deep vein thrombosis (DVT) Contraindication to prophylactic anticoagulation

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SGN-2FF<br>Dose escalation and dose expansion | Drug: SGN-2FF<br>* SGN-2FF oral daily dosing.<br>* Other names: 2-fluorofucose;|
| Experimental: SGN-2FF and Pembrolizumab<br>Dose escalation and dose expansion | Drug: SGN-2FF<br>* SGN-2FF oral daily dosing.<br>* Other names: 2-fluorofucose;Drug: pembrolizumab<br>* 200 mg every 3 weeks by IV infusion<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of participants with adverse events that are related to treatment | The number of patients who have side effects that are related to the study drug | Up to 90 days following last dose | 
| The number of participants with laboratory abnormalities that are related to treatment | The number of patients who have laboratory test results that are outside the normal range | Up to 90 days following last dose | 
| Incidence of dose-limiting toxicities (DLTs) | The rate of occurrence of side effects that prevent giving more of the treatment | 28 days from first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic assessments | Selected PK parameters, including area under the curve, maximum observed concentration, time to maximum observed concentration, and trough concentration. | Relative to most recent dosing event | 
| Markers of fucosylation status | Changes in pharmacodynamic biomarkers of fucosylation across dose levels | Up to 90 days following last dose | 
| Objective response rate | The proportion of patients who achieve a complete response (CR) or partial response (PR). | Up to 90 days following last dose | 
| Disease control rate | The proportion of patients who achieve either complete response (CR), partial response (PR), or stable disease (SD) | Up to approximately 5 years | 
| Duration of response | The time from the first documentation of objective response (CR or PR) to the first documentation of tumor progression (progressive disease per response criteria or clinical disease progression) or to death due to any cause, whichever comes first | Up to approximately 5 years | 
| Clinical benefit rate | The proportion of patients who achieve either complete response (CR), partial response (PR), or stable disease (SD) for at least 24 weeks | Up to approximately 5 years | 
| Progression-free survival | The time from start of study treatment to the first documentation of tumor progression (progressive disease per response criteria or clinical disease progression) or death due to any cause, whichever comes first | Up to approximately 5 years | 
| Overall survival | The time from start of study treatment to date of death due to any cause | Up to approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MSI-high, dMMR, PD-L1