Bladder Urothelial Carcinoma, Breast Cancer, Cholangiocarcinoma, Esophageal Cancer, Fallopian Tube Cancer, Gastric Cancer, Head and Neck Cancer, Hepatic Cancer, MSI-H Colorectal Cancer, Non-small Cell Lung Cancer, Other Solid Tumors, Ovarian Cancer, Primary Peritoneal Carcinoma, Renal Cell Carcinoma
Conditions
Brief summary
This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in patients with selected solid tumors.
Detailed description
This study will determine the safety, tolerability and activity of CDX-527. Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-527. The dose-escalation part of the study will determine the safety profile of CDX-527 and determine which dose(s) of CDX-527 will be studied in the expansion part of the study. The expansion part of the study will enroll eligible patients with certain solid tumors to be treated at dose(s) identified during dose-escalation Up to 40 patients will be enrolled. 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.
Interventions
DRUGCDX-527
CDX-527 is administered by infusion every 2 weeks
Sponsors
Celldex Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Recurrent, locally advanced or metastatic solid tumor cancer excluding the following: MSI-low colorectal cancer, glioblastoma multiforme, prostate cancer, pancreatic cancer, mucosal and ocular melanoma. 2. Receipt of all standard therapies for the tumor type 3. Measurable (target) disease by iRECIST 4. 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 5. Willingness to undergo a pre-treatment and on-treatment biopsy, if required Key
Exclusion criteria
1. History of severe hypersensitivity reactions to other monoclonal antibodies. 2. Previous treatment with any anti-CD27 antibody. 3. Inadequate washout period from prior therapy as defined in the Protocol. 4. Patients who have received more than 0 or 1 prior PD-1/PD-L1 inhibitor depending on their tumor type 5. Major surgery within 4 weeks prior to study treatment. 6. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to study treatment. 7. 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. 8. Thrombotic events within the last 6 months prior to study treatment 9. Active, untreated central nervous system metastases. 10. Active autoimmune disease or documented history of autoimmune disease. 11. History of (non-infectious) pneumonitis or has current pneumonitis. 12. Active diverticulitis 13. Known infection of HIV, Hepatitis B, or Hepatitis C. There are additional criteria your study doctor will review with you to confirm your eligibility for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of CDX-527 as assessed by CTCAE v5.0 | From first dose through 28 days after last dose | The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years. | The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months |
| Duration of Response | First occurrence of a documented objective response to disease progression or death (up to approximately 1-2 years) | The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented |
| Progression-free Survival | From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 years) | The time from start of study drug to time of progression or death, whichever occurs first |
| Objective Response Rate | Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years. | The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR) |
| Immunogenicity Evaluation | Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose | Serum samples will be obtained for assessment of human anti-CDX-527 antibodies |
| Pharmacokinetic Evaluation | Before and after dosing, with additional timepoints after the first two doses, then intermittently before dosing and up to 60 days after the last dose | CDX-527 serum concentrations will be measured at specified visits. |
| Overall Survival | The time from start of study drug to death from any cause (up to approximately 1-2 years) | The time from start of study drug to death |
Countries
United States
Outcome results
None listed