Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Adenocarcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Lymphoma, Large B-Cell, Diffuse

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasm Metastasis

Lung Neoplasms

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Follicular

Hodgkin Disease

Lymphoma, B-Cell

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Neoplasms, Glandular and Epithelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplastic Processes

B-cell Lymphoma

Lymphosarcoma

Follicular Lymphoma

Hodgkin Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Paclitaxel

Albumin-Bound Paclitaxel

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

SEA-CD40 (administered IV) + pembrolizumab

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

Given intravenously; schedule is cohort-specific.

Intravenous (IV) SEA-CD40

Given subcutaneously on Day 1 every 3 weeks

Subcutaneous (SC) SEA-CD40

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

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

Nab-paclitaxel

Michael Schmitt, MD, PhD

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.

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.

Safety Study of SEA-CD40 in Cancer Patients

A Phase 1, Open-label, Dose-escalation Study of SEA-CD40 in Adult Patients With Advanced Malignancies

Merck Sharp & Dohme LLC

Seagen Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety Study of SEA-CD40 in Cancer Patients	NCT02376699	Carcinoma, Non-... Carcinoma, Squa... Hodgkin Disease Lymphoma Lymphoma, B-Cel... Lymphoma, Folli... Lymphoma, Large... Melanoma Neoplasm Metast... Neoplasms, Head... Neoplasms, Squa... Non-Small Cell ... Non-Small Cell ... Non-small Cell ... Squamous Cell C... Squamous Cell C... Squamous Cell C... Squamous Cell N... Lymphoma, Non-H... Pancreatic Aden...	Intravenous (IV... Pembrolizumab Subcutaneous (S... Gemcitabine Nab-paclitaxel	18 Years -	Seagen Inc.
Safety Study of SEA-CD40 in Cancer Patients	NCT02376699	Carcinoma, Non-... Carcinoma, Squa... Hodgkin Disease Lymphoma Lymphoma, B-Cel... Lymphoma, Folli... Lymphoma, Large... Melanoma Neoplasm Metast... Neoplasms, Head... Neoplasms, Squa... Non-Small Cell ... Non-Small Cell ... Non-small Cell ... Squamous Cell C... Squamous Cell C... Squamous Cell C... Squamous Cell N... Lymphoma, Non-H... Pancreatic Aden...	Intravenous (IV... Pembrolizumab Subcutaneous (S... Gemcitabine Nab-paclitaxel	18 Years -	Seagen Inc.

Spots Global Cancer Trial Database for squamous cell neoplasm