NCT02376699

Safety Study of SEA-CD40 in Cancer Patients

A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 159 (actual)
• Sponsor: Seagen Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is being done to find out if SEA-CD40 is safe and effective when given alone, in combination with pembrolizumab, and in combination with pembrolizumab, gemcitabine, and nab-paclitaxel. The study will test increasing doses of SEA-CD40 given at least every 3 weeks to small groups of patients. The goal is to find the highest dose of SEA-CD40 that can be given to patients that does not cause unacceptable side effects. Different dose regimens will be evaluated. Different methods of administration may be evaluated. The pharmacokinetics, pharmacodynamic effects, biomarkers of response, and antitumor activity of SEA-CD40 will also be evaluated.

Detailed description

The study will be conducted in the following parts: Part A: Intravenous (IV) monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the IV SEA-CD40 monotherapy maximum tolerated dose (MTD) and/or the optimal biological dose (OBD) regimens in patients with solid tumors. The ability to increase the dose intensity (to give additional doses within a treatment cycle) may be evaluated. Part B: IV monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with doses at or below the IV SEA-CD40 monotherapy MTD and/or OBD determined in Part A. Part C: IV monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the IV SEA-CD40 monotherapy MTD and/or the OBD regimens in patients with lymphomas. The ability to increase the dose intensity (to give additional doses within a treatment cycle) may be evaluated. Part D: IV monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the IV SEA-CD40 monotherapy MTD and/or OBD determined in Part C. Part E: Combination therapy dose-regimen finding for solid tumors -- IV SEA-CD40 dose-escalation to define the MTD and/or the OBD regimen to be administered in combination with standard approved dose of pembrolizumab in patients with solid tumors. Part F: Combination therapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with IV SEA-CD40 and pembrolizumab combination therapy; doses of SEA-CD40 will be at or below the MTD and/or OBD determined in Part E. Part G: Subcutaneous (SC) injection (injected under the skin) monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the SC SEA-CD40 monotherapy maximum tolerated dose (MTD) and/or the optimal biological dose (OBD) regimens in patients with solid tumors. Part H: SC monotherapy solid tumor expansion cohorts -- Disease-specific solid tumor expansion cohorts may be enrolled where patients will be treated with doses at or below the SC SEA-CD40 monotherapy MTD and/or OBD determined in Part G. (Note: There is no Part I) Part J: SC monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the SC SEA-CD40 monotherapy MTD and/or the OBD regimens in patients with lymphomas. Part K: SC monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the SC SEA-CD40 monotherapy MTD and/or OBD determined in Part J. Part L: Combination therapy in pancreatic cancer -- Patients will be treated with SEA-CD40 doses at or below MTD and/or OBD. An established dose of pembrolizumab and a standard regimen of gemcitabine and nab-paclitaxel will be used. In Parts A, C, E, G, and J, a maximum feasible dose (MFD) will be defined if an MTD and/or OBD cannot be identified. Parts B, D, F, H, K. and L will explore the recommended dosing regimen once the MTD and/or OBD, or MFD (if the MTD and/or OBD cannot be identified) has been determined.

Conditions

• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Squamous Cell
• Hodgkin Disease
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Melanoma
• Neoplasm Metastasis
• Neoplasms, Head and Neck
• Neoplasms, Squamous Cell
• Non-Small Cell Lung Cancer
• Non-Small Cell Lung Cancer Metastatic
• Non-small Cell Carcinoma
• Squamous Cell Cancer
• Squamous Cell Carcinoma
• Squamous Cell Carcinoma of the Head and Neck
• Squamous Cell Neoplasm
• Lymphoma, Non-Hodgkin
• Pancreatic Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Intravenous (IV) SEA-CD40	Given intravenously; schedule is cohort-specific.
DRUG	Pembrolizumab	Given intravenously; schedule is cohort-specific.
DRUG	Subcutaneous (SC) SEA-CD40	Given subcutaneously on Day 1 every 3 weeks
DRUG	Gemcitabine	1000 mg/m\^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
DRUG	Nab-paclitaxel	125 mg/m\^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle

Timeline

• Start date: 2015-02-28
• Primary completion: 2023-03-06
• Completion: 2023-04-14
• First posted: 2015-03-03
• Last updated: 2023-05-01

Locations

19 sites across 1 country: United States