A Study of CDX-585 in Patients With Advanced Malignancies

Celldex Therapeutics20 enrolled

Overview

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

This study will determine the maximum tolerated dose of CDX-585 while also evaluating the safety, tolerability, and efficacy of CDX-585 in patients with cancer. Eligible patients that enroll to the dose-escalation portion of the study will be assigned to one of several dose levels of CDX-585. The dose-escalation part of the study will test the safety profile of CDX-585 and determine which dose of CDX-585 will be studied in the expansion portions of the study. 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. The expansion portion of the study will further evaluate the safety of CDX-585 in selected tumor types at the dose level chosen during the escalation part of the study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Non-small Cell Lung Cancer Gastric Cancer Head and Neck Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Recurrent, locally advanced, or metastatic solid tumor cancer excluding primary central nervous system tumors (e.g., glioblastoma). 2. Receipt of standard therapy for the tumor type in the recurrent, locally advanced, or metastatic setting. 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-ILT4 antibody. 3. Patients who have received more than 1 anti-PD-1 or anti-PD-L1 targeted therapy, including in the adjuvant setting. 4. Prior anti-PD-L1 based therapy within 12 weeks and prior anti-PD-1 based therapy within four weeks to the planned start of study treatment. 5. 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 one year to be allowed to enroll. 6. Thrombotic events within the last six months prior to study treatment 7. Active, untreated central nervous system metastases. 8. Active autoimmune disease or documented history of autoimmune disease. 9. History of (non-infectious) pneumonitis or has current pneumonitis. There are additional criteria your study doctor will review with you to confirm eligibility.

Outcomes

Primary Outcomes

Dose escalation: To determine the maximum tolerated dose of CDX-585 and to select the CDX-585 dose(s) for evaluation in tumor-specific expansion cohorts

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

Time frame: Approximately 12 months

Tumor-specific expansion cohorts: To further evaluate the safety of CDX-585 by tumor type.

The rates of drug-related adverse events will be summarized, and further evaluated in specific tumor types.

Time frame: Approximately 6 months

Secondary Outcomes

Safety and Tolerability of CDX-585 as assessed by CTCAE v5.0

The rates of drug-related adverse events will be summarized and evaluated.

Time frame: From first dose through 90 days after last dose

Objective Response Rate

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

Time frame: Assessed up to approximately 1-3 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

Time frame: Assessed up to approximately 1-3 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

Time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)

Progression-free Survival

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

Time frame: Cycle 1, day 1 to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)

Overall Survival

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 1-3 years)

Pharmacokinetic Evaluation

CDX-585 serum concentrations will be measured at specified visits

Time frame: Prior to, during, and at multiple time points after doses 1-4. Prior to every other dose from fifth dose, and at 30 and 90 days post last dose of study treatment

Immunogenicity Evaluation

Samples will be obtained for assessment of human anti-CDX-585

Time frame: Prior to the first three doses and every other dose from the fifth dose of study treatment, then 30 and 90 days after the last dose