NCT02376699

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
159

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Feb 2015

Longer than P75 for phase_1

Geographic Reach
1 country

19 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2015

Completed
11 days until next milestone

Study Start

First participant enrolled

February 28, 2015

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 3, 2015

Completed
8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 6, 2023

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

April 14, 2023

Completed
Last Updated

May 1, 2023

Status Verified

April 1, 2023

Enrollment Period

8 years

First QC Date

February 17, 2015

Last Update Submit

April 27, 2023

Conditions

Keywords

CD40 AntigenDrug TherapyFollicular LymphomaHodgkin DiseaseImmunotherapyIndolent LymphomaLymphomaLymphoma, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinMonoclonal AntibodyNeoplasmsNeoplasm MetastasisSolid tumorSeattle Genetics

Outcome Measures

Primary Outcomes (3)

  • Incidence of adverse events (Parts A-K)

    Through 6 weeks following last dose, up to an average of 6 months

  • Incidence of laboratory abnormalities (Parts A-K)

    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)

    Through 6 weeks following last dose, up to an average of 6 months

Secondary Outcomes (15)

  • Incidence of adverse events (Part L)

    Through 6 weeks following last dose, up to an average of 6 months

  • ORR per iRECIST (Part L)

    Through 6 weeks following last dose, up to an average of 6 months

  • ORR (Parts A-K)

    Through 6 weeks following last dose, up to an average of 6 months

  • Disease control rate (All Parts)

    Through 6 weeks following last dose, up to an average of 6 months

  • Duration of response (All Parts)

    Up to approximately 6 years

  • +10 more secondary outcomes

Study Arms (6)

IV Monotherapy in Solid Tumors

EXPERIMENTAL

SEA-CD40 administered IV

Drug: Intravenous (IV) SEA-CD40

IV Monotherapy in Lymphomas

EXPERIMENTAL

SEA-CD40 administered IV

Drug: Intravenous (IV) SEA-CD40

Combination Therapy in Solid Tumors

EXPERIMENTAL

SEA-CD40 (administered IV) + pembrolizumab

Drug: Intravenous (IV) SEA-CD40Drug: Pembrolizumab

SC Monotherapy in Solid Tumors

EXPERIMENTAL

SEA-CD40 administered SC

Drug: Subcutaneous (SC) SEA-CD40

SC Monotherapy in Lymphomas

EXPERIMENTAL

SEA-CD40 administered SC

Drug: Subcutaneous (SC) SEA-CD40

Combination Therapy in Pancreatic Cancer

EXPERIMENTAL

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

Drug: Intravenous (IV) SEA-CD40Drug: PembrolizumabDrug: GemcitabineDrug: Nab-paclitaxel

Interventions

Given intravenously; schedule is cohort-specific.

Also known as: SEA-CD40
Combination Therapy in Pancreatic CancerCombination Therapy in Solid TumorsIV Monotherapy in LymphomasIV Monotherapy in Solid Tumors

Given intravenously; schedule is cohort-specific.

Also known as: Keytruda
Combination Therapy in Pancreatic CancerCombination Therapy in Solid Tumors

Given subcutaneously on Day 1 every 3 weeks

Also known as: SEA-CD40
SC Monotherapy in LymphomasSC Monotherapy in Solid Tumors

1000 mg/m\^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle

Also known as: Gemzar
Combination Therapy in Pancreatic Cancer

125 mg/m\^2 given intravenously on Day 1, 8, and 15 of each 28-day cycle

Also known as: Abraxane
Combination Therapy in Pancreatic Cancer

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (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

You may not qualify if:

  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

HonorHealth Scottsdale Shea Medical Center

Scottsdale, Arizona, 85258, United States

Location

Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Angeles Clinic and Research Institute, The

Santa Monica, California, 90404, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637-1470, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030-4095, United States

Location

Utah Cancer Specialists

Salt Lake City, Utah, 84106, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Related Publications (1)

  • Coveler AL, Smith DC, Phillips T, Curti BD, Goel S, Mehta AN, Kuzel TM, Markovic SN, Rixe O, Bajor DL, Gajewski TF, Gutierrez M, Lee HJ, Gopal AK, Caimi P, Heath EI, Thompson JA, Ansari S, Jacquemont C, Topletz-Erickson A, Zhou P, Schmitt MW, Grilley-Olson JE. Phase 1 dose-escalation study of SEA-CD40: a non-fucosylated CD40 agonist, in advanced solid tumors and lymphomas. J Immunother Cancer. 2023 Jun;11(6):e005584. doi: 10.1136/jitc-2022-005584.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHodgkin DiseaseLymphomaLymphoma, B-CellLymphoma, FollicularLymphoma, Large B-Cell, DiffuseMelanomaNeoplasm MetastasisHead and Neck NeoplasmsNeoplasms, Squamous CellSquamous Cell Carcinoma of Head and NeckLymphoma, Non-HodgkinNeoplasms

Interventions

pembrolizumabInjections, SubcutaneousGemcitabine130-nm albumin-bound paclitaxelAlbumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteLung DiseasesRespiratory Tract DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsSkin DiseasesSkin and Connective Tissue DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

InjectionsDrug Administration RoutesDrug TherapyTherapeuticsHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingPaclitaxelTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesAlbuminsProteinsAmino Acids, Peptides, and Proteins

Study Officials

  • Michael Schmitt, MD, PhD

    Seagen Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 17, 2015

First Posted

March 3, 2015

Study Start

February 28, 2015

Primary Completion

March 6, 2023

Study Completion

April 14, 2023

Last Updated

May 1, 2023

Record last verified: 2023-04

Locations