Clinical trial NCT02376699: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: 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
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-03-03
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of adverse events (Parts A-K)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Incidence of laboratory abnormalities (Parts A-K)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Objective response rate (ORR) per RECIST according to investigator assessment in the efficacy-evaluable population (Part L)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
Secondary outcomes:
measure: Incidence of adverse events (Part L)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: ORR per iRECIST (Part L)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: ORR (Parts A-K)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Disease control rate (All Parts)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Duration of response (All Parts)
timeFrame: Up to approximately 6 years
measure: Progression-free survival (All Parts)
timeFrame: Up to approximately 6 years
measure: Overall survival (All Parts)
timeFrame: Up to approximately 6 years
measure: Cmax (maximum observed concentration)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Tmax (time of maximum observed concentration)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: AUClast (AUC from time 0 to last quantifiable timepoint)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: AUCinf (AUC from time 0 to infinity)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Apparent total clearance
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: T1/2 (apparent terminal elimination half-life)
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Incidence of antitherapeutic antibodies against SEA-CD40
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
measure: Blood concentrations of SEA-CD40
timeFrame: Through 6 weeks following last dose, up to an average of 6 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth Scottsdale Shea Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
state: California
city: Santa Monica
country: United States
facility: Angeles Clinic and Research Institute, The
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
Study officials:
affiliation: Seagen Inc.
name: Michael Schmitt, MD, PhD
role: STUDY_DIRECTOR
References: