Clinical trial NCT02952989: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Keywords: MSI-high
dMMR
PD-L1
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2016-11-02
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The number of participants with adverse events that are related to treatment
timeFrame: Up to 90 days following last dose
measure: The number of participants with laboratory abnormalities that are related to treatment
timeFrame: Up to 90 days following last dose
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 28 days from first dose
Secondary outcomes:
measure: Pharmacokinetic assessments
timeFrame: Relative to most recent dosing event
measure: Markers of fucosylation status
timeFrame: Up to 90 days following last dose
measure: Objective response rate
timeFrame: Up to 90 days following last dose
measure: Disease control rate
timeFrame: Up to approximately 5 years
measure: Duration of response
timeFrame: Up to approximately 5 years
measure: Clinical benefit rate
timeFrame: Up to approximately 5 years
measure: Progression-free survival
timeFrame: Up to approximately 5 years
measure: Overall survival
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital / University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
Study officials:
affiliation: Seagen Inc.
name: Christina Derleth, MD
role: STUDY_DIRECTOR
References: