A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies

Breast Cancer Clinical Trial

Official title:

A Phase 1 Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04440943
• Other study ID #: CDX527-01
• Status: Completed
• Phase: Phase 1
• Start date: August 4, 2020
• Est. completion date: April 6, 2023

Study information

• Verified date: June 2023
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in patients with selected solid tumors.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: April 6, 2023
• Est. primary completion date: April 6, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bladder Urothelial Carcinoma
• Breast Cancer
• Carcinoma
• Carcinoma, Renal Cell
• Cholangiocarcinoma
• Esophageal Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Gastric Cancer
• Head and Neck Cancer
• Hepatic Cancer
• Liver Neoplasms
• MSI-H Colorectal Cancer
• Non-small Cell Lung Cancer
• Other Solid Tumors
• Ovarian Cancer
• Primary Peritoneal Carcinoma
• Renal Cell Carcinoma

Intervention

Drug:
• CDX-527
CDX-527 is administered by infusion every 2 weeks

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia
United States	University of Chicago	Chicago	Illinois
United States	Duke Cancer Center	Durham	North Carolina
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	Providence Portland Medical Center	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of CDX-527 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 28 days after last dose
Secondary	Objective Response Rate	The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)	Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years.
Secondary	Clinical Benefit Rate	The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months	Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years.
Secondary	Duration of Response	The interval from which measurement criteria are first met for iCR or iPR 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 1-2 years)
Secondary	Progression-free Survival	The time from start of study drug to time of progression or death, whichever occurs first	From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 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 1-2 years)
Secondary	Immunogenicity Evaluation	Serum samples will be obtained for assessment of human anti-CDX-527 antibodies	Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose
Secondary	Pharmacokinetic Evaluation	CDX-527 serum concentrations will be measured at specified visits.	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