A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies
- Conditions
- Breast CancerGastric CancerFallopian Tube CancerOther Solid TumorsIndolent B-cell LymphomasWaldenstrom's DiseaseMarginal Zone LymphomaPancreatic AdenocarcinomaEsophageal CancerPrimary Peritoneal Cancer
- Interventions
- Registration Number
- NCT03329950
- Lead Sponsor
- Celldex Therapeutics
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 132
- 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.
- 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.
- 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
- Willingness to undergo a pre-treatment and on-treatment biopsy, if required.
Additional Inclusion Criteria for Part 1:
- Advanced diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, or indolent B-cell lymphoma are also eligible.
- Lymphoma patients must have received ≥ 1 prior systemic therapy
Additional Inclusion Criteria for Part 3:
- Patients must have documented progression while receiving anti-PD-1 or anti-PD-L1 based regimens for FDA approved indications
- Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen
Additional Inclusion Criteria for Part 4:
- Patients must have metastatic pancreatic adenocarcinoma, and have not received previous treatment in a metastatic setting
Key
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Previous treatment with any anti-CD40 antibody or with FLT3L.
- Inadequate washout period from prior therapy as defined in the Protocol.
- Major surgery within 4 weeks prior to study treatment.
- Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment.
- 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.
- Active, untreated central nervous system metastases.
- Active autoimmune disease or documented history of autoimmune disease.
- History of (non-infectious) pneumonitis or has current pneumonitis.
- Active infection requiring systemic therapy, known infection of HIV, Hepatitis B, or Hepatitis C.
Additional Exclusion Criteria for lymphoma patients in Part 1:
- Prior allogenic stem cell transplantation
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CDX-1140 and CDX-301 CDX-1140 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. CDX-1140 and pembrolizumab CDX-1140 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. CDX-1140 and CDX-301 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. CDX-1140 and chemotherapy 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. CDX-1140 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. CDX-1140 and chemotherapy CDX-1140 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. CDX-1140 and pembrolizumab 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.
- Primary Outcome Measures
Name Time Method Safety and Tolerability of CDX-1140 as assessed by CTCAE v5.0 From first dose through 30 days after last dose The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.
- Secondary Outcome Measures
Name Time Method Progression-free survival From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years) The time from start of study drug to time of progression or death, whichever occurs first
Clinical benefit rate Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least four months
Duration of Response First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years) The interval from which measurement criteria are first met for CR or PR until the first date that progressive disease is objectively documented
Objective Response Rate Every 8-12 weeks, starting with first dose until disease progression, assessed up to approximately 1-3 years. 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).
Overall survival The time from start of study drug to death from any cause (up to approximately 1-3 years) The time from start of study drug to death
Immunogenicity evaluation Prior to each dose of study treatment and at treatment discontinuation, up to approximately 1-3 years Serum samples will be obtained for assessment of human anti-CDX-1140 and anti-CDX-301 antibodies
Pharmacokinetic evaluation Prior to each study treatment, multiple timepoints after each study treatment, and at treatment discontinuation up to approximately 1-3 years CDX-1140 and CDX-301 concentrations will be measured
Trial Locations
- Locations (11)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Houston Methodist
🇺🇸Houston, Texas, 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
HonorHealth Research Insititute
🇺🇸Scottsdale, Arizona, 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
Rhode Island Hospital (RIH) The Miriam Hospital (TMH)
🇺🇸Providence, Rhode Island, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States