CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer

NCT05029999 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SCCC-03121; STU-2021-0657
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

This research study is being done to find out if the immunotherapy drugs called CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment pegylated liposomal doxorubicin (PLD, Doxil) are safe and effective at controlling the cancer in patients with metastatic triple Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer, and to determine a safe dose and treatment schedule of the three drugs. This research study will also test how your immune system responds to these treatments alone and in combination.

Conditions

HER2-negative Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Safety (tolerability) of the drug combination of CDX-1140, CDX-301 and PLD as measured by the number of participants with Dose Limiting Toxicity (DLT)

  DLTs are defined as toxicities that meet pre-defined severity criteria including serious Hematologic/Non-Hematologic adverse events (AEs) and AEs at Grade 3 or above; Any ≥ grade 2 eye pain or reduction of visual acuity that does not improved to ≤ grade 1 severity within 2 weeks of initiation of topical therapy or requires systemic treatment. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

  Baseline up to 12 months

Secondary Outcomes (6)

• Anti-tumor immune response by on-treatment CD8 T cell infiltrate

  After Cycle 1 (~4 weeks)

• Change in CD8 T cell infiltrate

  Baseline, After Cycle 1 (~4 weeks)

• Median Progression Free Survival by RECIST v1.1 with administration of CDX-1140, CDX-301, and PLD chemotherapy.

  Baseline until date of first observed disease progression or death, assessed up to12 months

• Overall Response Rate(ORR) by RECIST v1.1 with administration of CDX-1140, CDX-301, and PLD chemotherapy.

  Baseline until date of first observed objective tumor response assessed up to12 months

• Duration of Response(DoR) by RECIST v1.1 to CDX-1140, CDX-301, and PLD chemotherapy.

  Date of response until progression or death from any cause, assessed up to 12 months

Study Arms (2)

Cohort A

EXPERIMENTAL

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle until toxicity or progression. CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle until toxicity or progression for up to 24 months. CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 days cycles 1 and 2 only.

Drug: PLD Chemotherapy; Drug: CDX-1140; Drug: CDX-301

Cohort C

EXPERIMENTAL

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle until toxicity or progression. CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle starting on cycle 2 until toxicity or progression for up to 24 months. CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 days cycles 2 and 3 only.

Drug: PLD Chemotherapy; Drug: CDX-1140; Drug: CDX-301

Interventions

PLD Chemotherapy DRUG

PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle.

Also known as: Pegylated liposomal doxorubicin

Cohort A; Cohort C

CDX-1140 DRUG

CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle.

Also known as: CD40 monoclonal antibody

Cohort A; Cohort C

CDX-301 DRUG

CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 doses per cycle for 2 cycles.

Also known as: Flt3 Ligand

Cohort A; Cohort C

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unresectable Stage III or Stage IV HER2 negative breast cancer (either triple negative or hormone receptor positive)
• Triple negative breast cancer for this study is defined as estrogen receptor \<10%, progesterone receptor \<10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
• Hormone receptor positive breast cancer for this study is defined as either estrogen receptor ≥10% or progesterone receptor ≥10% by immunohistochemistry, and HER2- negative by Herceptest (0 or 1+) or not amplified by in situ hybridization as per routine clinical testing.
• Age 18 years or older
• Performance status ECOG 0-2
• Life expectancy ≥ 12 weeks
• Documented progressive disease, based on radiographic, clinical or pathologic assessment, during or subsequent to last anticancer therapy. Patients who need to change systemic therapy for other indications such as toxicity that are otherwise eligible for this study may enroll with approval of the lead principal investigator.
• For triple negative breast cancer patients, subject is in first to fourth line setting of treatment for metastatic or unresectable disease, and have received 0 to 3 prior regimens for metastatic or unresectable disease.
• For hormone receptor positive breast cancer patients, subjects must have received prior cyclin dependent kinase inhibitor in the metastatic setting. They may have received up to 3 prior lines of chemotherapy and/or antibody drug conjugates for metastatic or unresectable disease.
• Among triple negative breast cancer patients enrolled in the first line treatment setting, subjects must be PD-L1 negative by 22C3 assay and not be eligible for FDA approved standard of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical trial. This does not apply if patients have previously received PD-1 or PD-L1 blockade as part of neoadjuvant or adjuvant therapy regimen.
• Screening laboratory values must meet the following criteria:
• Neutrophils ≥ 1500/uL
• Platelets ≥ 100 x10(9)/L
• Hemoglobin ≥ 8 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Creatinine ≤ 2 mg/dL

You may not qualify if:

• Among any patients enrolled in the first line treatment setting, tumors should not be PD-L1+ by 22C3 assays or eligible for FDA approved standard of care chemotherapy and anti-PD-1/PD-L1 combination therapy as alternative to this clinical trial. This does not apply if patients have previously received PD-1 or PD-L1 blockade as part of neoadjuvant or adjuvant therapy regimen.
• History of severe hypersensitivity reactions to mAbs.
• Prior treatment with any anti-CD40 antibody or rhuFlt3L product.
• Treatment with anthracycline in the metastatic setting.
• Prior progression while on anthracycline based therapy or within 6 months of completing neoadjuvant or adjuvant anthracycline.
• Prior history of acute myeloid leukemia (AML), or tumor with known Flt3 mutation/amplification
• Receipt of any antibody targeting T cell check point or co-stimulation pathways within 4 weeks, use of any other monoclonal based therapies within 4 weeks, and all other immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) within 2 weeks prior to the planned start of study treatment.
• Prior T-cell or other cell-based therapies within 12 weeks (or 2 weeks if patient experienced disease progression on the prior treatment)
• Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
• Chemotherapy or antibody drug conjugate within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
• Any kinase inhibitors within 2 weeks prior to the first dose of study treatment.
• Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
• Use of other investigational drugs within 4 weeks or 5 half-lives (whichever is longer) prior to study treatment administration.
• Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment. Topical, inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if the patient is on a stable dose. Non-absorbed intraarticular corticosteroid and replacement steroids (≤ 10 mg/day prednisone or equivalent) will be permitted.
• Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Celldex Therapeutics: collaborator
• Gateway for Cancer Research: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (7)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

WITHDRAWN

Texas Oncology, P.A.

Dallas, Texas, 75251, United States

ACTIVE NOT RECRUITING

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

liposomal doxorubicin; flt3 ligand protein

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Sangeetha Reddy

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meredith Carter, MS

CONTACT

(214) 648-7020; Meredith.carter@utsouthwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 1, 2021
• Study Start: April 20, 2022
• Primary Completion: April 20, 2026
• Study Completion: April 20, 2026
• Last Updated: August 13, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)