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A Study of CDX-585 in Patients With Advanced Malignancies

Phase 1
Active, not recruiting
Conditions
Colorectal Cancer
Esophageal Cancer
Non-small Cell Lung Cancer
Ovarian Cancer
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Bladder Urothelial Carcinoma
Hepatic Cancer
Gastric Cancer
Head and Neck Cancer
Interventions
Drug: CDX-585
Registration Number
NCT05788484
Lead Sponsor
Celldex Therapeutics
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 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.

Approximately 130 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.

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
130
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

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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.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
CDX-585CDX-585Dose-escalation phase: Eligible patients will receive treatment, based on cohort assigned, in 2-week cycles until progression or intolerance. Expansion phase: Patients enrolled in the expansion phase of the study will receive CDX-585 at the dose level chosen during the escalation phase.
Primary Outcome Measures
NameTimeMethod
Tumor-specific expansion cohorts: To further evaluate the safety of CDX-585 by tumor type.Approximately 6 months

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

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 cohortsApproximately 12 months

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

Secondary Outcome Measures
NameTimeMethod
Safety and Tolerability of CDX-585 as assessed by CTCAE v5.0From first dose through 90 days after last dose

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

Pharmacokinetic EvaluationPrior 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

CDX-585 serum concentrations will be measured at specified visits

Progression-free SurvivalCycle 1, day 1 to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years)

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

Objective Response RateAssessed up to approximately 1-3 years.

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

Duration of ResponseFirst occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years)

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

Clinical Benefit RateAssessed up to approximately 1-3 years.

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

Overall SurvivalThe time from start of study drug to death from any cause (up to approximately 1-3 years)

The time from start of study drug to death

Immunogenicity EvaluationPrior 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

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

Trial Locations

Locations (4)

George Washington University Cancer Center

🇺🇸

Washington, District of Columbia, United States

AdventHealth Celebration

🇺🇸

Celebration, Florida, United States

Perlmutter Cancer Center at NYU Langone Health

🇺🇸

New York, New York, United States

Providence Cancer Institute

🇺🇸

Portland, Oregon, United States

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