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Safety Study of SEA-CD40 in Cancer Patients

Primary Purpose

Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Hodgkin Disease

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Intravenous (IV) SEA-CD40
Pembrolizumab
Subcutaneous (SC) SEA-CD40
Gemcitabine
Nab-paclitaxel
Sponsored by
Seagen Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring CD40 Antigen, Drug Therapy, Follicular Lymphoma, Hodgkin Disease, Immunotherapy, Indolent Lymphoma, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Monoclonal Antibody, Neoplasms, Neoplasm Metastasis, Solid tumor, Seattle Genetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- 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])
  • (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- 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
  • (Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed advanced or metastatic solid malignancy for which pembrolizumab treatment is approved. In Part F, other advanced solid tumor indications may be eligible as identified by the Sponsor.
  • (Pancreatic Cancer Cohort - Part L) - Histologically or cytologically confirmed metastatic exocrine ductal adenocarcinoma of the pancreas not amenable to curative therapy. Patients must not have received any prior systemic therapy for metastatic disease; patients who have received prior therapy for non-metastatic pancreatic adenocarcinoma are eligible if therapy was fully completed more than 4 months before start of study treatment.
  • Representative baseline tumor tissue sample is available (Parts A-K)
  • 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 attributed to prior anticancer therapy prior to initiation of study drug administration

Exclusion Criteria:

  • Parts A-K

    1. Prior chemotherapy, small molecule inhibitors, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies) within 4 weeks
    2. Prior radiotherapy: therapeutic radiotherapy within 4 weeks, or palliative radiotherapy (to non-CNS disease) within 1 week
    3. Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology doublet used as the prior line of therapy)
    4. Prior monoclonal antibodies, antibody-drug conjugates, or radioimmunoconjugates within 4 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
    5. Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
  • Part L

    1. History of radiation pneumonitis
    2. Neuropathy Grade 2 or higher
    3. Has received prior therapy with an anti-PD-1, anti-PDL1, or anti-PD-L2 agent, with an agent directed to another stimulatory or co-inhibitory T-cell receptor
    4. Has had allogenic tissue/solid organ transplant
  • All Parts

    1. Recent or ongoing serious infections within 2 weeks
    2. Known positivity for hepatitis B infection
    3. Known active hepatitis C infection
    4. Active autoimmune or auto-inflammatory ocular disease within 6 months
    5. Known or suspected active organ-threatening autoimmune disease
    6. Active central nervous system tumor or metastases
  • Patients with lymphomas: prior allogeneic SCT
  • Patients in Part E, F, or L: history of severe immune-mediated adverse reactions or severe hypersensitivity to pembrolizumab

Sites / Locations

  • University of Alabama at Birmingham
  • HonorHealth Scottsdale Shea Medical Center
  • Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
  • Angeles Clinic and Research Institute, The
  • Rush University Medical Center
  • University of Chicago Medical Center
  • University of Michigan Comprehensive Cancer Center
  • Karmanos Cancer Institute / Wayne State University
  • Mayo Clinic Rochester
  • Comprehensive Cancer Centers of Nevada
  • Hackensack University Medical Center
  • University of New Mexico Cancer Center
  • Montefiore Medical Center
  • UNC Lineberger Comprehensive Cancer Center / University of North Carolina
  • Case Western Reserve University / University Hospitals Cleveland Medical Center
  • Providence Portland Medical Center
  • MD Anderson Cancer Center / University of Texas
  • Utah Cancer Specialists
  • Seattle Cancer Care Alliance / University of Washington

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

IV Monotherapy in Solid Tumors

IV Monotherapy in Lymphomas

Combination Therapy in Solid Tumors

SC Monotherapy in Solid Tumors

SC Monotherapy in Lymphomas

Combination Therapy in Pancreatic Cancer

Arm Description

SEA-CD40 administered IV

SEA-CD40 administered IV

SEA-CD40 (administered IV) + pembrolizumab

SEA-CD40 administered SC

SEA-CD40 administered SC

SEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel

Outcomes

Primary Outcome Measures

Incidence of adverse events (Parts A-K)
Incidence of laboratory abnormalities (Parts A-K)
Objective response rate (ORR) per RECIST according to investigator assessment in the efficacy-evaluable population (Part L)

Secondary Outcome Measures

Incidence of adverse events (Part L)
ORR per iRECIST (Part L)
ORR (Parts A-K)
Disease control rate (All Parts)
Duration of response (All Parts)
Progression-free survival (All Parts)
Overall survival (All Parts)
Cmax (maximum observed concentration)
Tmax (time of maximum observed concentration)
AUClast (AUC from time 0 to last quantifiable timepoint)
AUCinf (AUC from time 0 to infinity)
Apparent total clearance
T1/2 (apparent terminal elimination half-life)
Incidence of antitherapeutic antibodies against SEA-CD40
Blood concentrations of SEA-CD40

Full Information

First Posted
February 17, 2015
Last Updated
April 27, 2023
Sponsor
Seagen Inc.
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02376699
Brief Title
Safety Study of SEA-CD40 in Cancer Patients
Official Title
A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Terminated
Why Stopped
Study closed due to portfolio prioritization
Study Start Date
February 28, 2015 (Actual)
Primary Completion Date
March 6, 2023 (Actual)
Study Completion Date
April 14, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
CD40 Antigen, Drug Therapy, Follicular Lymphoma, Hodgkin Disease, Immunotherapy, Indolent Lymphoma, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Monoclonal Antibody, Neoplasms, Neoplasm Metastasis, Solid tumor, Seattle Genetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV Monotherapy in Solid Tumors
Arm Type
Experimental
Arm Description
SEA-CD40 administered IV
Arm Title
IV Monotherapy in Lymphomas
Arm Type
Experimental
Arm Description
SEA-CD40 administered IV
Arm Title
Combination Therapy in Solid Tumors
Arm Type
Experimental
Arm Description
SEA-CD40 (administered IV) + pembrolizumab
Arm Title
SC Monotherapy in Solid Tumors
Arm Type
Experimental
Arm Description
SEA-CD40 administered SC
Arm Title
SC Monotherapy in Lymphomas
Arm Type
Experimental
Arm Description
SEA-CD40 administered SC
Arm Title
Combination Therapy in Pancreatic Cancer
Arm Type
Experimental
Arm Description
SEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel
Intervention Type
Drug
Intervention Name(s)
Intravenous (IV) SEA-CD40
Other Intervention Name(s)
SEA-CD40
Intervention Description
Given intravenously; schedule is cohort-specific.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Given intravenously; schedule is cohort-specific.
Intervention Type
Drug
Intervention Name(s)
Subcutaneous (SC) SEA-CD40
Other Intervention Name(s)
SEA-CD40
Intervention Description
Given subcutaneously on Day 1 every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
1000 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Nab-paclitaxel
Other Intervention Name(s)
Abraxane
Intervention Description
125 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
Primary Outcome Measure Information:
Title
Incidence of adverse events (Parts A-K)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Incidence of laboratory abnormalities (Parts A-K)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Objective response rate (ORR) per RECIST according to investigator assessment in the efficacy-evaluable population (Part L)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Secondary Outcome Measure Information:
Title
Incidence of adverse events (Part L)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
ORR per iRECIST (Part L)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
ORR (Parts A-K)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Disease control rate (All Parts)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Duration of response (All Parts)
Time Frame
Up to approximately 6 years
Title
Progression-free survival (All Parts)
Time Frame
Up to approximately 6 years
Title
Overall survival (All Parts)
Time Frame
Up to approximately 6 years
Title
Cmax (maximum observed concentration)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Tmax (time of maximum observed concentration)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
AUClast (AUC from time 0 to last quantifiable timepoint)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
AUCinf (AUC from time 0 to infinity)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Apparent total clearance
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
T1/2 (apparent terminal elimination half-life)
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Incidence of antitherapeutic antibodies against SEA-CD40
Time Frame
Through 6 weeks following last dose, up to an average of 6 months
Title
Blood concentrations of SEA-CD40
Time Frame
Through 6 weeks following last dose, up to an average of 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- 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]) (Monotherapy - Parts A, B, C, D, G, H, J, and K) -- 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 (Combination Therapy - Part E and Part F) -- Histologically or cytologically confirmed advanced or metastatic solid malignancy for which pembrolizumab treatment is approved. In Part F, other advanced solid tumor indications may be eligible as identified by the Sponsor. (Pancreatic Cancer Cohort - Part L) - Histologically or cytologically confirmed metastatic exocrine ductal adenocarcinoma of the pancreas not amenable to curative therapy. Patients must not have received any prior systemic therapy for metastatic disease; patients who have received prior therapy for non-metastatic pancreatic adenocarcinoma are eligible if therapy was fully completed more than 4 months before start of study treatment. Representative baseline tumor tissue sample is available (Parts A-K) 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 attributed to prior anticancer therapy prior to initiation of study drug administration Exclusion Criteria: Parts A-K Prior chemotherapy, small molecule inhibitors, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies) within 4 weeks Prior radiotherapy: therapeutic radiotherapy within 4 weeks, or palliative radiotherapy (to non-CNS disease) within 1 week Prior immune-checkpoint inhibitors within 4 weeks (or 8 weeks, if immuno-oncology doublet used as the prior line of therapy) 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) Part L History of radiation pneumonitis Neuropathy Grade 2 or higher Has received prior therapy with an anti-PD-1, anti-PDL1, or anti-PD-L2 agent, with an agent directed to another stimulatory or co-inhibitory T-cell receptor Has had allogenic tissue/solid organ transplant All Parts 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 Active central nervous system tumor or metastases Patients with lymphomas: prior allogeneic SCT Patients in Part E, F, or L: history of severe immune-mediated adverse reactions or severe hypersensitivity to pembrolizumab
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Schmitt, MD, PhD
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
HonorHealth Scottsdale Shea Medical Center
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Angeles Clinic and Research Institute, The
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Karmanos Cancer Institute / Wayne State University
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Case Western Reserve University / University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4095
Country
United States
Facility Name
Utah Cancer Specialists
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Seattle Cancer Care Alliance / University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States

12. IPD Sharing Statement

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Safety Study of SEA-CD40 in Cancer Patients

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