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

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

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

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma; Breast Cancer; Head and Neck Cancer; Gastric Cancer; Esophageal Cancer; Ovarian Cancer; Fallopian Tube Cancer; Cholangiocarcinoma; Non-small Cell Lung Cancer; Primary Peritoneal Carcinoma; Hepatic Cancer; Bladder Urothelial Carcinoma; Other Solid Tumors; MSI-H Colorectal Cancer
• Intervention / Treatment: Drug: CDX-527

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.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDX-527; Dose-escalation phase: Eligible patients will receive CDX-527 treatment based on cohort assigned until progression or intolerance. Expansion phase: Patients will receive CDX-527 at the dose level(s) chosen during the escalation phase.	Drug: CDX-527; CDX-527 is administered by infusion every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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)
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)
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)
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
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

Collaborators and Investigators

• Sponsor: Celldex Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): April 6, 2023
• Study Completion (Actual): April 6, 2023

Study Registration Dates

• First Submitted: June 11, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 22, 2020

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Adnexal Diseases; Digestive System Neoplasms; Liver Diseases; Kidney Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Carcinoma, Renal Cell; Carcinoma; Fallopian Tube Neoplasms; Cholangiocarcinoma; Liver Neoplasms
• Other Study ID Numbers: CDX527-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No