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Safety Study of SEA-CD40 in Cancer Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02376699
Recruitment Status : Active, not recruiting
First Posted : March 3, 2015
Last Update Posted : May 19, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Seagen Inc.

Tracking Information
First Submitted Date  ICMJE February 17, 2015
First Posted Date  ICMJE March 3, 2015
Last Update Posted Date May 19, 2022
Actual Study Start Date  ICMJE February 28, 2015
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 6, 2019)
  • Incidence of adverse events (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Incidence of laboratory abnormalities (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2019)
  • Incidence of adverse events (Part L) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • ORR per iRECIST (Part L) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • ORR (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Disease control rate (All Parts) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Duration of response (All Parts) [ Time Frame: Up to approximately 6 years ]
  • Progression-free survival (All Parts) [ Time Frame: Up to approximately 6 years ]
  • Overall survival (All Parts) [ Time Frame: Up to approximately 6 years ]
  • Cmax (maximum observed concentration) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Tmax (time of maximum observed concentration) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • AUClast (AUC from time 0 to last quantifiable timepoint) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • AUCinf (AUC from time 0 to infinity) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Apparent total clearance [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • T1/2 (apparent terminal elimination half-life) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Incidence of antitherapeutic antibodies against SEA-CD40 [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
  • Blood concentrations of SEA-CD40 [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2015)
  • 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 3 years ]
  • Progression-free survival [ Time Frame: Up to approximately 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of SEA-CD40 in Cancer Patients
Official Title  ICMJE A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Intravenous (IV) SEA-CD40
    Given intravenously; schedule is cohort-specific.
    Other Name: SEA-CD40
  • Drug: Pembrolizumab
    Given intravenously; schedule is cohort-specific.
    Other Name: Keytruda
  • Drug: Subcutaneous (SC) SEA-CD40
    Given subcutaneously on Day 1 every 3 weeks
    Other Name: SEA-CD40
  • Drug: Gemcitabine
    1000 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
    Other Name: Gemzar
  • Drug: Nab-paclitaxel
    125 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
    Other Name: Abraxane
Study Arms  ICMJE
  • Experimental: IV Monotherapy in Solid Tumors
    SEA-CD40 administered IV
    Intervention: Drug: Intravenous (IV) SEA-CD40
  • Experimental: IV Monotherapy in Lymphomas
    SEA-CD40 administered IV
    Intervention: Drug: Intravenous (IV) SEA-CD40
  • Experimental: Combination Therapy in Solid Tumors
    SEA-CD40 (administered IV) + pembrolizumab
    Interventions:
    • Drug: Intravenous (IV) SEA-CD40
    • Drug: Pembrolizumab
  • Experimental: SC Monotherapy in Solid Tumors
    SEA-CD40 administered SC
    Intervention: Drug: Subcutaneous (SC) SEA-CD40
  • Experimental: SC Monotherapy in Lymphomas
    SEA-CD40 administered SC
    Intervention: Drug: Subcutaneous (SC) SEA-CD40
  • Experimental: Combination Therapy in Pancreatic Cancer
    SEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel
    Interventions:
    • Drug: Intravenous (IV) SEA-CD40
    • Drug: Pembrolizumab
    • Drug: Gemcitabine
    • Drug: Nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 12, 2021)
159
Original Estimated Enrollment  ICMJE
 (submitted: February 25, 2015)
144
Estimated Study Completion Date  ICMJE October 31, 2024
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02376699
Other Study ID Numbers  ICMJE SGNS40-001
PN 863 ( Other Identifier: Merck Sharp & Dohme Corp )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Seagen Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Seagen Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Merck Sharp & Dohme LLC
Investigators  ICMJE
Study Director: Michael Schmitt, MD, PhD Seagen Inc.
PRS Account Seagen Inc.
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP