NCT05029999

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

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

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.

Conditions

• HER2-negative Breast Cancer
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	PLD Chemotherapy	PLD chemotherapy will be administered 40 mg/m2 as intravenous injection once per cycle.
DRUG	CDX-1140	CDX-1140 will be administered 1.5mg/kg as intravenous injection once per cycle.
DRUG	CDX-301	CDX-301 will be administered 75µg/kg as subcutaneous injection daily x 5 doses per cycle for 2 cycles.

Timeline

• Start date: 2022-04-20
• Primary completion: 2026-04-20
• Completion: 2026-04-20
• First posted: 2021-09-01
• Last updated: 2025-08-13

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study