Clinical trial NCT04440943: A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies
Official title: A Phase 1 Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Non-small Cell Lung Cancer
Breast Cancer
Gastric Cancer
Renal Cell Carcinoma
Ovarian Cancer
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Cholangiocarcinoma
Bladder Urothelial Carcinoma
MSI-H Colorectal Cancer
Esophageal Cancer
Hepatic Cancer
Head and Neck Cancer
Other Solid Tumors
Lead sponsor: Celldex Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-06-22
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability of CDX-527 as assessed by CTCAE v5.0
timeFrame: From first dose through 28 days after last dose
Secondary outcomes:
measure: Objective Response Rate
timeFrame: Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years.
measure: Clinical Benefit Rate
timeFrame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years.
measure: Duration of Response
timeFrame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-2 years)
measure: Progression-free Survival
timeFrame: From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 years)
measure: Overall Survival
timeFrame: The time from start of study drug to death from any cause (up to approximately 1-2 years)
measure: Immunogenicity Evaluation
timeFrame: Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose
measure: Pharmacokinetic Evaluation
timeFrame: 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
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
Study officials:
References: