A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies

NCT ID: NCT03329950

Last Updated: 2024-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 132 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-01
• Study Completion Date: 2022-09-13

Brief Summary

This is a study to determine the maximum tolerated dose (MTD) for CDX-1140 (CD40 antibody), either alone or in combination with CDX-301 (FLT3L), pembrolizumab, or chemotherapy and to further evaluate its tolerability and efficacy in expansion cohorts once the MTD is determined.

Detailed Description

This study will determine the MTD of CDX-1140 while also evaluating the safety, tolerability and efficacy of CDX-1140 alone (Part 1) or in combination with CDX-301 (Part 2), pembrolizumab (Part 3), or chemotherapy (Part 4) in patients with cancer.

Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-1140. The dose-escalation part of the study will test the safety profile of CDX-1140, alone or in combination with CDX-301, pembrolizumab or chemotherapy and determine which dose(s) of CDX-1140 will be studied in the expansion portions of the study.

All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.

Conditions

Melanoma; Non-small Cell Lung Cancer; Breast Cancer; Gastric Cancer; Renal Cell Carcinoma; Ovarian Cancer; Cholangiocarcinoma; Bladder Urothelial Carcinoma; Pancreatic Adenocarcinoma; Colorectal Cancer; Esophageal Cancer; Hepatic Cancer; Head and Neck Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer; Other Solid Tumors; Diffuse Large B-cell Lymphoma (DLBCL); Mantle Cell Lymphoma; Indolent B-cell Lymphomas; Non-Hodgkin Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Waldenstrom's Disease; Marginal Zone Lymphoma; Mucosa Associated Lymphoid Tissue; Small Lymphocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CDX-1140

Part 1: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance, or two years of treatment.

Group Type: EXPERIMENTAL

CDX-1140

Intervention Type: DRUG

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

CDX-1140 and CDX-301

Part 2: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, intolerance or two years of treatment. A fixed dose of CDX-301 is injected once a day for five days before cycles 1 and 2 of CDX-1140.

Group Type: EXPERIMENTAL

CDX-1140

Intervention Type: DRUG

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

CDX-301

Intervention Type: DRUG

CDX-301 will be injected once a day for five days before Cycles 1 and 2.

CDX-1140 and pembrolizumab

Part 3: Eligible patients will receive CDX-1140, based on cohort assigned, in 3 week cycles until progression, or intolerance, or two years of treatment. A fixed dose of pembrolizumab will also be given in 3 week cycles.

Group Type: EXPERIMENTAL

CDX-1140

Intervention Type: DRUG

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

pembrolizumab

Intervention Type: DRUG

pembrolizumab will be administered every 3 weeks.

CDX-1140 and chemotherapy

Part 4: Eligible patients will receive CDX-1140, based on cohort assigned, in 4 week cycles until progression, or intolerance, or two years of treatment. Chemotherapy will also be given according to standard of care.

Group Type: EXPERIMENTAL

CDX-1140

Intervention Type: DRUG

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

Chemotherapy

Intervention Type: DRUG

Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

Interventions

CDX-1140

CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.

Intervention Type: DRUG

CDX-301

CDX-301 will be injected once a day for five days before Cycles 1 and 2.

Intervention Type: DRUG

pembrolizumab

pembrolizumab will be administered every 3 weeks.

Intervention Type: DRUG

Chemotherapy

Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

Intervention Type: DRUG

Other Intervention Names

KEYTRUDA®

Eligibility Criteria

Inclusion Criteria

1. Recurrent, locally advanced or metastatic melanoma (including mucosal and/or ocular), bladder/urothelial, non-small cell lung cancer, pancreatic adenocarcinoma, breast, colorectal, gastric, esophageal, renal cell, hepatic, ovarian fallopian or primary peritoneal carcinoma, head and neck, and cholangiocarcinoma. Additional tumor types (except primary CNS tumors) may be enrolled after discussion with, and approval from, the medical monitor.

2. Must have received all standard of care therapies (approved or unapproved) as deemed appropriate by the treating physician. Patients who refuse standard therapy are excluded from the study.

3. If of childbearing potential (male or female), agrees to practice an effective form of contraception during study treatment and for at least 3 months following last treatment

4. Willingness to undergo a pre-treatment and on-treatment biopsy, if required.

1. Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.

2. Lymphoma patients must have received ≥ 1 prior systemic therapy

1. Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1 based regimens for FDA approved indications

2. Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen

1. Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting

Exclusion Criteria

1. History of severe hypersensitivity reactions to other monoclonal antibodies.

2. Previous treatment with any anti-CD40 antibody or with FLT3L.

3. Inadequate washout period from prior therapy as defined in the Protocol.

4. Major surgery within 4 weeks prior to study treatment.

5. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.

6. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers. For all other cancers, the patient must be disease-free for at least 3 years to be allowed to enroll.

7. Active, untreated central nervous system metastases.

8. Active autoimmune disease or documented history of autoimmune disease.

9. History of (non-infectious) pneumonitis or has current pneumonitis.

10. Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.

1. Prior allogenic stem cell transplantation

2. Patients who have received autologous stem cell transplant ≤ 12 weeks prior to the first dose of study drug.

There are additional criteria your study doctor will review with you to confirm your eligibility for the study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Celldex Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

HonorHealth Research Insititute

Scottsdale, Arizona, United States

Northside Hospital, Inc.

Atlanta, Georgia, United States

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States

Oncology Hematology West, PC dba Nebraska Cancer Specialists

Omaha, Nebraska, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Gabrail Cancer Center Research LLC

Canton, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Abramson Cancer Center at the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Rhode Island Hospital (RIH) The Miriam Hospital (TMH)

Providence, Rhode Island, United States

Houston Methodist

Houston, Texas, United States

Countries

United States

Other Identifiers

KEYNOTE-A23

Identifier Type: OTHER

Identifier Source: secondary_id

CDX1140-01

Identifier Type: -

Identifier Source: org_study_id