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CD40 Agonist, Flt3 Ligand, and Chemotherapy in HER2 Negative Breast Cancer | Clinical Trials | Clareo Health

RECRUITINGPHASE1

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

Phase 1 Pilot Study With Dose Expansion of Chemotherapy in Combination With CD40 Agonist and Flt3 Ligand in Metastatic HER2 Negative Breast Cancer

NCT05029999•University of Texas Southwestern Medical Center

View on ClinicalTrials.gov

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.

Detailed Description

The immunotherapy drugs CDX-301 and CDX-1140 in combination with the standard chemotherapy treatment PLD work by kickstarting the immune response against cancer cells. CDX-301 increases the antigen presenting immune cells needed to kickstart the immune response, CDX-1140 activates these cells, and chemotherapy helps release antigens from the cancer cells to train these antigen presenting immune cells to recognize the cancer for the immune system to attack it. Metastatic or unresectable triple negative breast cancer patients will receive this triplet combination that has been shown in preclinical studies to be more effective than the individual treatments or doublet combinations. To understand how the immunotherapies are working, some patients will receive the immunotherapy or chemotherapy only for one cycle prior to receiving the full triplet combination therapy. Ultimately, all patients will receive the triplet combination to study safety and how effective this treatment is at controlling triple negative breast cancer and improving survival outcomes. The original design of the project includes 3 cohorts (arms). In February 2024 Cohort B (experimental arm) was closed to further enrollment. Cohort B includes the following design: PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle starting on cycle 2 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.

Eligibility

Age

18 - 99 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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.
+16 more criteria

Exclusion Criteria

•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.
+17 more criteria

Locations (7)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Johns Hopkins University

Baltimore, Maryland, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Texas Oncology, P.A.

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Key Dates

Start Date

April 20, 2022

Primary Completion Date

April 20, 2026

Completion Date

April 20, 2026

Last Updated

August 13, 2025

Enrollment

ESTIMATED participants

Conditions

HER2-negative Breast CancerMetastatic Breast Cancer

Interventions

PLD Chemotherapy

DRUG

CDX-1140

DRUG

CDX-301

DRUG

Contacts

Meredith Carter, MS

CONTACT

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

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: August 13, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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