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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

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

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
IV Monotherapy in Solid Tumors
SEA-CD40 administered IV
  • Drug: Intravenous (IV) SEA-CD40
    Given intravenously; schedule is cohort-specific.
    Other names:
    • SEA-CD40
Experimental
IV Monotherapy in Lymphomas
SEA-CD40 administered IV
  • Drug: Intravenous (IV) SEA-CD40
    Given intravenously; schedule is cohort-specific.
    Other names:
    • SEA-CD40
Experimental
Combination Therapy in Solid Tumors
SEA-CD40 (administered IV) + pembrolizumab
  • Drug: Intravenous (IV) SEA-CD40
    Given intravenously; schedule is cohort-specific.
    Other names:
    • SEA-CD40
  • Drug: Pembrolizumab
    Given intravenously; schedule is cohort-specific.
    Other names:
    • Keytruda
Experimental
SC Monotherapy in Solid Tumors
SEA-CD40 administered SC
  • Drug: Subcutaneous (SC) SEA-CD40
    Given subcutaneously on Day 1 every 3 weeks
    Other names:
    • SEA-CD40
Experimental
SC Monotherapy in Lymphomas
SEA-CD40 administered SC
  • Drug: Subcutaneous (SC) SEA-CD40
    Given subcutaneously on Day 1 every 3 weeks
    Other names:
    • SEA-CD40
Experimental
Combination Therapy in Pancreatic Cancer
SEA-CD40 (administered IV) + pembrolizumab + gemcitabine + nab-paclitaxel
  • Drug: Intravenous (IV) SEA-CD40
    Given intravenously; schedule is cohort-specific.
    Other names:
    • SEA-CD40
  • Drug: Pembrolizumab
    Given intravenously; schedule is cohort-specific.
    Other names:
    • Keytruda
  • Drug: Gemcitabine
    1000 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
    Other names:
    • Gemzar
  • Drug: Nab-paclitaxel
    125 mg/m^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle
    Other names:
    • Abraxane

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10467
Contact:
Mohammad Ghalib
718-405-8515
mhghalib@montefiore.org

More Details

NCT ID
NCT02376699
Status
Recruiting
Sponsor
Seattle Genetics, Inc.

Study Contact

Seattle Genetics Trial Information Support
866-333-7436
clinicaltrials@seagen.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.