A Phase 1 Dose-escalation and Expansion Study of the PD-1 x ILT4 Bispecific Antibody CDX-585 in Patients With Advanced Malignancies
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Celldex Therapeutics
- Enrollment
- 20
- Locations
- 4
- Primary Endpoint
- Tumor-specific expansion cohorts: To further evaluate the safety of CDX-585 by tumor type.
Study Overview
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.
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Recurrent, locally advanced, or metastatic solid tumor cancer excluding primary central nervous system tumors (e.g., glioblastoma).
- •Receipt of standard therapy for the tumor type in the recurrent, locally advanced, or metastatic setting.
- •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.
Exclusion Criteria
- •History of severe hypersensitivity reactions to other monoclonal antibodies.
- •Previous treatment with any anti-ILT4 antibody.
- •Patients who have received more than 1 anti-PD-1 or anti-PD-L1 targeted therapy, including in the adjuvant setting.
- •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.
- •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.
- •Thrombotic events within the last six 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.
- •There are additional criteria your study doctor will review with you to confirm eligibility.
Arms & Interventions
CDX-585
Dose-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.
Intervention: CDX-585 (Drug)
Outcomes
Primary Outcomes
Tumor-specific expansion cohorts: To further evaluate the safety of CDX-585 by tumor type.
Time Frame: 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 cohorts
Time Frame: Approximately 12 months
The rates of drug-related adverse events will be summarized, and maximum tolerated dose will be determined.
Secondary Outcomes
- Safety and Tolerability of CDX-585 as assessed by CTCAE v5.0(From first dose through 90 days after last dose)
- Pharmacokinetic Evaluation(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)
- Progression-free Survival(Cycle 1, day 1 to the first occurrence of disease progression or death due to any cause (up to approximately 1-3 years))
- Objective Response Rate(Assessed up to approximately 1-3 years.)
- Duration of Response(First occurrence of a documented objective response to disease progression or death (up to approximately 1-3 years))
- Clinical Benefit Rate(Assessed up to approximately 1-3 years.)
- Overall Survival(The time from start of study drug to death from any cause (up to approximately 1-3 years))
- Immunogenicity Evaluation(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)