Safety Study of SEA-CD40 in Cancer Patients

• ClinicalTrials.gov Identifier: NCT02376699
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2015
• Last Update Posted: February 8, 2023
• Sponsor: Seagen Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Seagen Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: Intravenous (IV) SEA-CD40; Drug: Pembrolizumab; Drug: Subcutaneous (SC) SEA-CD40; Drug: Gemcitabine; Drug: Nab-paclitaxel	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 159 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies
• Actual Study Start Date: February 28, 2015
• Estimated Primary Completion Date: January 31, 2024
• Estimated Study Completion Date: October 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: IV Monotherapy in Solid Tumors; SEA-CD40 administered IV	Drug: Intravenous (IV) SEA-CD40; Given intravenously; schedule is cohort-specific.; Other Name: SEA-CD40
Experimental: IV Monotherapy in Lymphomas; SEA-CD40 administered IV	Drug: Intravenous (IV) SEA-CD40; Given intravenously; schedule is cohort-specific.; Other Name: 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 Name: SEA-CD40; Drug: Pembrolizumab; Given intravenously; schedule is cohort-specific.; Other Name: 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 Name: 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 Name: 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 Name: SEA-CD40; Drug: Pembrolizumab; Given intravenously; schedule is cohort-specific.; Other Name: Keytruda; 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

Outcome Measures

Primary Outcome Measures :

1. Incidence of adverse events (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
2. Incidence of laboratory abnormalities (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
3. 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 ]

Secondary Outcome Measures :

1. Incidence of adverse events (Part L) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
2. ORR per iRECIST (Part L) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
3. ORR (Parts A-K) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
4. Disease control rate (All Parts) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
5. Duration of response (All Parts) [ Time Frame: Up to approximately 6 years ]
6. Progression-free survival (All Parts) [ Time Frame: Up to approximately 6 years ]
7. Overall survival (All Parts) [ Time Frame: Up to approximately 6 years ]
8. Cmax (maximum observed concentration) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
9. Tmax (time of maximum observed concentration) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
10. AUClast (AUC from time 0 to last quantifiable timepoint) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
11. AUCinf (AUC from time 0 to infinity) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
12. Apparent total clearance [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
13. T1/2 (apparent terminal elimination half-life) [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
14. Incidence of antitherapeutic antibodies against SEA-CD40 [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]
15. Blood concentrations of SEA-CD40 [ Time Frame: Through 6 weeks following last dose, up to an average of 6 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35249

United States, Arizona

HonorHealth Scottsdale Shea Medical Center

Scottsdale, Arizona, United States, 85258

United States, California

Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, United States, 90048

Angeles Clinic and Research Institute, The

Santa Monica, California, United States, 90404

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

University of Chicago Medical Center

Chicago, Illinois, United States, 60637-1470

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic Rochester

Rochester, Minnesota, United States, 55905

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87131

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

United States, North Carolina

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

Chapel Hill, North Carolina, United States, 27599

United States, Ohio

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States, 44106

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

United States, Texas

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States, 77030-4095

United States, Utah

Utah Cancer Specialists

Salt Lake City, Utah, United States, 84106

United States, Washington

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, United States, 98109-1023

Sponsors and Collaborators

Seagen Inc.

Merck Sharp & Dohme LLC

Investigators

• Study Director: Michael Schmitt, MD, PhD; Seagen Inc.

More Information

• Responsible Party: Seagen Inc.
• ClinicalTrials.gov Identifier: NCT02376699
• Other Study ID Numbers: SGNS40-001; PN 863 ( Other Identifier: Merck Sharp & Dohme Corp )
• First Posted: March 3, 2015
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Keywords provided by Seagen Inc.:

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

Additional relevant MeSH terms:

Lymphoma; Carcinoma; Lung Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Neoplasm Metastasis; Squamous Cell Carcinoma of Head and Neck; Hodgkin Disease; Lymphoma, Non-Hodgkin; Neoplasms, Squamous Cell; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Head and Neck Neoplasms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Pathologic Processes