Safety Study of SEA-CD40 in Cancer Patients

ID: NCT02376699
Status: Recruiting
Phase: Phase 1
Start Date: February 01, 2015
First Submitted: February 17, 2015
Last Updated: January 30, 2018
Results: N/A
Sponsors & Collaborators: Seattle Genetics, Inc.
Location: United States
Conditions: Cancer, Carcinoma, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Hematologic Malignancies, Hodgkin Disease, Lymphoma, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Melanoma, Neoplasms, 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
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Study Description

Brief Summary

This study will examine the safety profile of SEA-CD40 given alone and in combination with pembrolizumab. 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. 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: Monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the 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: 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 SEA-CD40 monotherapy MTD and/or OBD determined in Part A.

Part C: Monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the 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: Monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the SEA-CD40 monotherapy MTD and/or OBD determined in Part C.

Part E: Combination therapy dose-regimen finding for solid tumors -- 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 SEA-CD40 and pembrolizumab combination therapy; doses of SEA-CD40 will be at or below the MTD and/or OBD determined in Part E.
Condition or disease Intervention/treatment Phase

Cancer

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Hematologic Malignancies

Hodgkin Disease

Lymphoma

Lymphoma, B-Cell

Lymphoma, Follicular

Lymphoma, Large B-Cell, Diffuse

Lymphoma, Non-Hodgkin

Melanoma

Neoplasm Metastasis

Neoplasms

Neoplasms, Head and Neck

Neoplasms, Squamous Cell

Non-small Cell Carcinoma

Non-Small Cell Lung Cancer

Non-Small Cell Lung Cancer Metastatic

Squamous Cell Cancer

Squamous Cell Carcinoma

Squamous Cell Carcinoma of the Head and Neck

Squamous Cell Neoplasm

Drug: SEA-CD40 monotherapy regimen
Other Names
SEA-CD40
Drug: Pembrolizumab
Other Names
Keytruda
Phase 1

Tracking Information

First Submitted DateFebruary 17, 2015
Last Update Posted DateJanuary 30, 2018
Start DateFebruary 01, 2015
Anticipated Completion DateJuly 01, 2021
Primary Completion DateApril 01, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Incidence of adverse events [Time Frame: Through up to approximately 6 weeks following last dose]

  • Incidence of chemistry and hematology laboratory abnormalities [Time Frame: Through up to approximately 6 weeks following last dose]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Blood concentrations of SEA-CD40 [Time Frame: Through up to approximately 6 weeks after dosing]

  • Incidence of antitherapeutic antibodies against SEA-CD40 [Time Frame: Through up to approximately 6 weeks after dosing]

  • Mean absolute and percent change from baseline over time of selected pharmacodynamic markers [Time Frame: Through up to approximately 6 weeks after dosing]

  • Objective response rate [Time Frame: Through up to approximately 6 weeks following last dose]

  • Disease control rate [Time Frame: Through up to approximately 6 weeks following last dose]

  • Duration of response [Time Frame: Up to approximately 6 years]

  • Progression-free survival [Time Frame: Up to approximately 6 years]

  • Overall survival [Time Frame: Up to approximately 6 years]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleSafety Study of SEA-CD40 in Cancer Patients
Official TitleA Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies
Brief Summary

This study will examine the safety profile of SEA-CD40 given alone and in combination with pembrolizumab. 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. 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: Monotherapy dose-regimen finding for solid tumors -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the 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: 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 SEA-CD40 monotherapy MTD and/or OBD determined in Part A.

Part C: Monotherapy dose-regimen finding for lymphomas -- Dose-escalation, and possible dose-interval modification to lengthen the treatment cycle, to define the 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: Monotherapy lymphoma expansion cohorts -- Disease-specific lymphoma expansion cohorts may be enrolled where patients will be treated with doses at or below the SEA-CD40 monotherapy MTD and/or OBD determined in Part C.

Part E: Combination therapy dose-regimen finding for solid tumors -- 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 SEA-CD40 and pembrolizumab combination therapy; doses of SEA-CD40 will be at or below the MTD and/or OBD determined in Part E.

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
290
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Cancer
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Hematologic Malignancies
Hodgkin Disease
Lymphoma
Lymphoma, B-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Melanoma
Neoplasm Metastasis
Neoplasms
Neoplasms, Head and Neck
Neoplasms, Squamous Cell
Non-small Cell Carcinoma
Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer Metastatic
Squamous Cell Cancer
Squamous Cell Carcinoma
Squamous Cell Carcinoma of the Head and Neck
Squamous Cell Neoplasm
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: SEA-CD40 monotherapy regimen

Given intravenously on Day 1 every 3 weeks; or Days 1 and 8 every 3 weeks for 2 cycles, and then Day 1 every 3 weeks in subsequent cycles. Number of cycles: until progression or unacceptable toxicity develops.

Other Names
SEA-CD40
Drug: Pembrolizumab

Given intravenously on Day 2 every 3 weeks. Number of cycles: until progression or unacceptable toxicity develops.

Other Names
Keytruda
Study Groups/Cohorts
Monotherapy in Solid Tumors
SEA-CD40

Monotherapy in Lymphomas
SEA-CD40

Combination Therapy in Solid Tumors
SEA-CD40 + pembrolizumab

Study Arms
Experimental Combination Therapy in Solid Tumors
SEA-CD40 + pembrolizumab
Drug : SEA-CD40 monotherapy regimen
Given intravenously on Day 1 every 3 weeks; or Days 1 and 8 every 3 weeks for 2 cycles, and then Day 1 every 3 weeks in subsequent cycles. Number of cycles: until progression or unacceptable toxicity develops.

Experimental Combination Therapy in Solid Tumors
SEA-CD40 + pembrolizumab
Drug : Pembrolizumab
Given intravenously on Day 2 every 3 weeks. Number of cycles: until progression or unacceptable toxicity develops.

Experimental Monotherapy in Lymphomas
SEA-CD40
Drug : SEA-CD40 monotherapy regimen
Given intravenously on Day 1 every 3 weeks; or Days 1 and 8 every 3 weeks for 2 cycles, and then Day 1 every 3 weeks in subsequent cycles. Number of cycles: until progression or unacceptable toxicity develops.

Experimental Monotherapy in Solid Tumors
SEA-CD40
Drug : SEA-CD40 monotherapy regimen
Given intravenously on Day 1 every 3 weeks; or Days 1 and 8 every 3 weeks for 2 cycles, and then Day 1 every 3 weeks in subsequent cycles. Number of cycles: until progression or unacceptable toxicity develops.

Arm Intervention/Treatment
Experimental Combination Therapy in Solid Tumors
SEA-CD40 + pembrolizumab
Drug : SEA-CD40 monotherapy regimen
Experimental Combination Therapy in Solid Tumors
SEA-CD40 + pembrolizumab
Drug : Pembrolizumab
Experimental Monotherapy in Lymphomas
SEA-CD40
Drug : SEA-CD40 monotherapy regimen
Experimental Monotherapy in Solid Tumors
SEA-CD40
Drug : SEA-CD40 monotherapy regimen

Recruitment Information

Recruitment Status:Recruiting
Enrollment290
Completion DateJuly 01, 2021
Eligibility Criteria: Inclusion Criteria:
- (Parts A, B, C, and D) -- Histologically confirmed advanced malignancy, either: (a) Metastatic or unresectable solid malignancy; or (b) Classical Hodgkin lymphoma (HL), or diffuse large B-cell lymphoma (DLBCL), or indolent lymphoma (including follicular lymphoma [FL])
- (Parts A, B, C, and D) -- Relapsed, refractory, or progressive disease, specifically: (a) Solid tumors: Following at least 1 prior systemic therapy, and no further standard therapy is available for the patient's advanced solid tumor at the time of enrollment; or (b) Classical HL: Following at least 2 prior systemic therapies in patients who are not candidates for autologous stem cell transplant (SCT), or following failure of autologous SCT; or (c) DLBCL: Following at least 1 prior systemic therapy; patients must have also received intensive salvage therapy unless they refused or were deemed ineligible; or (d) Indolent lymphoma: Following at least 1 prior chemoimmunotherapy regimen that included an anti-CD20 monoclonal antibody and for which no other more appropriate treatment option exists
- (Part E and Part F) -- Histologically confirmed advanced solid malignancy for which pembrolizumab treatment is approved
- Representative baseline tumor tissue sample is available
- Measurable disease
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate baseline hematologic, renal, and hepatic function
- Recovery to Grade 1 of any clinically significant toxicity prior to initiation of study drug administration

Exclusion Criteria:
- Prior chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies) within 2 weeks
- Prior immune-checkpoint inhibitors within 4 weeks
- Prior monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates within 4 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
- Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
- Recent or ongoing serious infections within 2 weeks
- Known positivity for hepatitis B infection
- Known active hepatitis C infection
- Active autoimmune or auto-inflammatory ocular disease within 6 months
- Known or suspected active organ-threatening autoimmune disease
- Prior or current central nervous system tumor or metastases
- Patients with lymphomas: prior allogeneic SCT
- Patients in Part E or Part F: history of severe immune-mediated adverse reactions to pembrolizumab
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02376699
Other Study ID Numbers
SGNS40-001
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Seattle Genetics, Inc.
Collaborators
Not Available
Investigators
Study Director
Thomas Manley, MD
Seattle Genetics, Inc.