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

• ClinicalTrials.gov Identifier: NCT02952989
• Recruitment Status: Terminated
• First Posted: November 2, 2016
• Last Update Posted: July 19, 2019
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: October 27, 2016
• First Posted Date: November 2, 2016
• Last Update Posted Date: July 19, 2019
• Actual Study Start Date: February 23, 2017
• Actual Primary Completion Date: June 24, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 8, 2018)

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

Original Primary Outcome Measures (submitted: October 31, 2016)

• The number of participants with adverse events that are related to treatment [ Time Frame: Through 1 month following last dose ]
• The number of participants with laboratory abnormalities that are related to treatment [ Time Frame: Through 1 month following last dose ]
• Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 28 days from first dose ]

Current Secondary Outcome Measures (submitted: March 8, 2018)

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

Original Secondary Outcome Measures (submitted: October 31, 2016)

• Estimate of area under the concentration-time curve [ Time Frame: Through 1 month following last dose ]
• Estimate of maximum concentration [ Time Frame: Through 1 month following last dose ]
• Estimate of time to maximum concentration [ Time Frame: Through 1 month following last dose ]
• Estimate of trough concentration [ Time Frame: Through 1 month following last dose ]
• Markers of fucosylation status [ Time Frame: Through 1 month following last dose ]
• Objective response rate [ Time Frame: Through 1 month following last dose ]
• Disease control rate [ Time Frame: Up to approximately 5 years ]
• Duration of response [ Time Frame: Up to approximately 5 years ]
• Clinical benefit rate [ Time Frame: Up to approximately 5 years ]
• Progression-free survival [ Time Frame: Up to approximately 5 years ]
• Overall survival [ Time Frame: Up to approximately 5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

• Drug: SGN-2FF
  SGN-2FF oral daily dosing.
  Other Name: 2-fluorofucose
• Drug: pembrolizumab
  200 mg every 3 weeks by IV infusion
  Other Name: Keytruda

Study Arms

• Experimental: SGN-2FF
  Dose escalation and dose expansion
  Intervention: Drug: SGN-2FF
• Experimental: SGN-2FF and Pembrolizumab
  Dose escalation and dose expansion
  Interventions:

  • Drug: SGN-2FF
  • Drug: pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 8, 2019): 47
• Original Estimated Enrollment (submitted: October 31, 2016): 158
• Actual Study Completion Date: June 24, 2019
• Actual Primary Completion Date: June 24, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02952989
• Other Study ID Numbers: SGN2FF-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Christina Derleth, MD; Seagen Inc.

• PRS Account: Seagen Inc.
• Verification Date: July 2019