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

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

Detailed Description
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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.

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

Conditions
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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

Intervention / Treatment
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* Drug: CDX-527


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDX-527<br>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<br>* CDX-527 is administered by infusion every 2 weeks<br>|

What is the study measuring?
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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 |