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

Primary Purpose

Non-small Cell Lung Cancer, Breast Cancer, Gastric Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

CDX-527

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

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.
Receipt of all standard therapies for the tumor type
Measurable (target) disease by iRECIST
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

Key Exclusion Criteria:

History of severe hypersensitivity reactions to other monoclonal antibodies.
Previous treatment with any anti-CD27 antibody.
Inadequate washout period from prior therapy as defined in the Protocol.
Patients who have received more than 0 or 1 prior PD-1/PD-L1 inhibitor depending on their tumor type
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.
Thrombotic events within the last 6 months prior to study treatment
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 diverticulitis
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.

Sites / Locations

Northside Hospital
University of Chicago
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Duke Cancer Center
Providence Portland Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CDX-527

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Objective Response Rate

The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)

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

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

Progression-free Survival

The time from start of study drug to time of progression or death, whichever occurs first

Overall Survival

The time from start of study drug to death

Immunogenicity Evaluation

Serum samples will be obtained for assessment of human anti-CDX-527 antibodies

Pharmacokinetic Evaluation

CDX-527 serum concentrations will be measured at specified visits.

Full Information

NCT ID

NCT04440943

First Posted

June 11, 2020

Last Updated

June 16, 2023

Sponsor

Celldex Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04440943

Brief Title

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

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

August 4, 2020 (Actual)

Primary Completion Date

April 6, 2023 (Actual)

Study Completion Date

April 6, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Celldex Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CDX-527

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

CDX-527

Intervention Description

CDX-527 is administered by infusion every 2 weeks

Primary Outcome Measure Information:

Title

Safety and Tolerability of CDX-527 as assessed by CTCAE v5.0

Description

The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.

Time Frame

From first dose through 28 days after last dose

Secondary Outcome Measure Information:

Title

Objective Response Rate

Description

The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)

Time Frame

Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years.

Title

Clinical Benefit Rate

Description

The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months

Time Frame

Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years.

Title

Duration of Response

Description

The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented

Time Frame

First occurrence of a documented objective response to disease progression or death (up to approximately 1-2 years)

Title

Progression-free Survival

Description

The time from start of study drug to time of progression or death, whichever occurs first

Time Frame

From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 years)

Title

Overall Survival

Description

The time from start of study drug to death

Time Frame

The time from start of study drug to death from any cause (up to approximately 1-2 years)

Title

Immunogenicity Evaluation

Description

Serum samples will be obtained for assessment of human anti-CDX-527 antibodies

Time Frame

Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose

Title

Pharmacokinetic Evaluation

Description

CDX-527 serum concentrations will be measured at specified visits.

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: 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. Receipt of all standard therapies for the tumor type Measurable (target) disease by iRECIST 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 Key Exclusion Criteria: History of severe hypersensitivity reactions to other monoclonal antibodies. Previous treatment with any anti-CD27 antibody. Inadequate washout period from prior therapy as defined in the Protocol. Patients who have received more than 0 or 1 prior PD-1/PD-L1 inhibitor depending on their tumor type 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. Thrombotic events within the last 6 months prior to study treatment 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 diverticulitis 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.

Facility Information:

Facility Name

Northside Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

University of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Oncology Hematology West, PC dba Nebraska Cancer Specialists

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68130

Country

United States

Facility Name

Duke Cancer Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Providence Portland Medical Center

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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