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

Breast Cancer Clinical Trial

Official title:

A Phase 1 Study of CDX-1140 as Monotherapy or in Combination in Patients With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03329950
• Other study ID #: CDX1140-01
• Secondary ID: KEYNOTE-A23
• Status: Completed
• Phase: Phase 1
• Start date: December 1, 2017
• Est. completion date: September 13, 2022

Study information

• Verified date: March 2024
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: September 13, 2022
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

Additional Inclusion Criteria for Part 1:

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

Additional Inclusion Criteria for Part 3:

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

Additional Inclusion Criteria for Part 4:

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

Key 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.

Additional Exclusion Criteria for lymphoma patients in Part 1:

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• CDX-1140
CDX-1140 will be administered every 4 weeks in Parts 1, 2 and 4, and every 3 weeks in Part 3.
• CDX-301
CDX-301 will be injected once a day for five days before Cycles 1 and 2.
• pembrolizumab
pembrolizumab will be administered every 3 weeks.
• Chemotherapy
Gemcitabine and Nab-paclitaxel will be administered on Day 1, Day 8 and Day 15 of each 4 week Cycle.

Locations

Country	Name	City	State
United States	Northside Hospital, Inc.	Atlanta	Georgia
United States	Georgia Cancer Center at Augusta University	Augusta	Georgia
United States	Gabrail Cancer Center Research LLC	Canton	Ohio
United States	Houston Methodist	Houston	Texas
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	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Abramson Cancer Center at the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Rhode Island Hospital (RIH) The Miriam Hospital (TMH)	Providence	Rhode Island
United States	HonorHealth Research Insititute	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Celldex Therapeutics	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0	The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.	From first dose through 30 days after last dose
Secondary	Objective Response Rate	The percentage of patients who achieved a confirmed complete response or partial response by evaluation criteria in solid tumors for immune-based therapeutics (iRECIST; for solid tumor patients) and the lymphoma response to immunomodulatory therapy criteria (LYRIC; for lymphoma patients).	Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years.
Secondary	Clinical benefit rate	The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months	Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years
Secondary	Duration of Response	The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented	First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)
Secondary	Progression-free survival	The time from start of study drug to time of progression or death, whichever occurs first	From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)
Secondary	Overall survival	The time from start of study drug to death	The time from start of study drug to death from any cause (up to approximately 1-3 years)
Secondary	Immunogenicity evaluation	Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies	Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years
Secondary	Pharmacokinetic evaluation	CDX-1140 and CDX-301 concentrations will be measured	Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years