Clinical Trials /

Safety Study of SEA-CD40 in Cancer Patients

NCT02376699

Description:

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.

Related Conditions:
  • Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoma
  • Malignant Solid Tumor
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: SGNS40-001
  • SECONDARY ID: PN 863
  • NCT ID: NCT02376699

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
  • Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
Intravenous (IV) SEA-CD40SEA-CD40IV Monotherapy in Solid Tumors
PembrolizumabKeytrudaCombination Therapy in Solid Tumors
Subcutaneous (SC) SEA-CD40SEA-CD40SC Monotherapy in Solid Tumors
GemcitabineGemzarCombination Therapy in Pancreatic Cancer
Nab-paclitaxelAbraxaneCombination Therapy in Pancreatic Cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
IV Monotherapy in Solid TumorsExperimentalSEA-CD40 administered IV
  • Intravenous (IV) SEA-CD40
IV Monotherapy in LymphomasExperimentalSEA-CD40 administered IV
  • Intravenous (IV) SEA-CD40
Combination Therapy in Solid TumorsExperimentalSEA-CD40 (administered IV) + pembrolizumab
  • Intravenous (IV) SEA-CD40
  • Pembrolizumab
SC Monotherapy in Solid TumorsExperimentalSEA-CD40 administered SC
  • Subcutaneous (SC) SEA-CD40
SC Monotherapy in LymphomasExperimentalSEA-CD40 administered SC
  • Subcutaneous (SC) SEA-CD40
Combination Therapy in Pancreatic CancerExperimentalSEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel
  • Intravenous (IV) SEA-CD40
  • Pembrolizumab
  • Gemcitabine
  • Nab-paclitaxel

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

               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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (Parts A-K)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence of adverse events (Part L)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:ORR per iRECIST (Part L)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:ORR (Parts A-K)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Disease control rate (All Parts)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Duration of response (All Parts)
Time Frame:Up to approximately 6 years
Safety Issue:
Description:
Measure:Progression-free survival (All Parts)
Time Frame:Up to approximately 6 years
Safety Issue:
Description:
Measure:Overall survival (All Parts)
Time Frame:Up to approximately 6 years
Safety Issue:
Description:
Measure:Cmax (maximum observed concentration)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Tmax (time of maximum observed concentration)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:AUClast (AUC from time 0 to last quantifiable timepoint)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:AUCinf (AUC from time 0 to infinity)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Apparent total clearance
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:T1/2 (apparent terminal elimination half-life)
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Incidence of antitherapeutic antibodies against SEA-CD40
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:
Measure:Blood concentrations of SEA-CD40
Time Frame:Through 6 weeks following last dose, up to an average of 6 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Trial 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

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