Immunotherapy + Chemotherapy for Triple Negative Breast Cancer

Recruiting at 5 trial locations

Overseen By Meredith Carter, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, Corticosteroids, Anthracyclines, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two immunotherapy drugs, CDX-301 and CDX-1140, with the chemotherapy drug Doxil (Pegylated Liposomal Doxorubicin) is safe and effective for individuals with triple-negative breast cancer, a type that has spread and lacks the HER2 protein. Researchers seek to identify the optimal dose and schedule while assessing the immune system's response to these treatments. The trial seeks participants with advanced breast cancer that cannot be surgically removed and is worsening despite previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like immunotherapy, chemotherapy, and some other medications must be stopped for a specific period before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CDX-1140, when combined with pembrolizumab, is generally well-tolerated. The most common serious side effects can be managed, indicating that CDX-1140 might be safe for many patients.

CDX-301 effectively increases certain important blood cells without major safety concerns, which is a positive sign for its safety in humans.

Pegylated liposomal doxorubicin (PLD) is already used to treat some cancers. Studies have indicated it is safe for long-term use, even in older patients or those at risk for heart problems, suggesting a good safety profile for PLD.

In summary, early results show that CDX-1140 and CDX-301 are generally well-tolerated. PLD is already known to be safe for many patients. However, this combination is new. The trial aims to confirm safety and determine the best dose. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for triple negative breast cancer because they combine innovative immunotherapy agents, CDX-1140 and CDX-301, with standard chemotherapy. Unlike traditional chemotherapy, which attacks cancer cells directly, CDX-1140 is an antibody that stimulates the immune system by targeting a protein called CD40, potentially enhancing the body's own ability to fight cancer. CDX-301, on the other hand, boosts the production of dendritic cells, which are crucial for launching an immune response. This combination aims to not only attack cancer cells but also empower the immune system, offering a two-pronged approach that could improve outcomes in a cancer type notoriously difficult to treat.

What evidence suggests that this trial's treatments could be effective for metastatic triple negative breast cancer?

Research shows that CDX-1140, one of the treatments in this trial, has demonstrated promising early results in combating difficult cancers when combined with other treatments. In some studies, it worked well with pembrolizumab, another cancer drug, and showed potential in shrinking tumors. CDX-301, another treatment option in this trial, increases certain immune cells, enhancing the body's ability to fight cancer. For pegylated liposomal doxorubicin (PLD), also part of this trial, research found it effective in treating advanced breast cancer, achieving a disease control rate of 51.3% in some patients, while causing fewer side effects compared to standard doxorubicin. Together, these drugs aim to harness the immune system to improve outcomes for patients with triple-negative breast cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Sangeetha Reddy, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with metastatic triple negative breast cancer who have a life expectancy of at least 12 weeks. They should be in their first to third line of treatment and may have had up to two prior regimens. Participants must not be pregnant, agree to use contraception, and cannot have certain health conditions or treatments that would conflict with the trial.

Inclusion Criteria

I have at least one cancer lesion that can be measured over time.

My cancer has worsened despite treatment, or I had to stop treatment due to side effects.

I agree to have biopsies before and during treatment, from areas that haven't been irradiated and are safe to biopsy.

Exclusion Criteria

Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.

I do not have serious heart problems or recent major heart events.

I haven't taken any kinase inhibitors in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CDX-301, CDX-1140, and PLD chemotherapy in cycles. CDX-301 is administered daily for 5 days in cycles 1 and 2, CDX-1140 is administered once per cycle for up to 24 months, and PLD is administered once per cycle until toxicity or progression.

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of overall response rate and progression-free survival.

12 months

Extension

Participants may continue to receive treatment until disease progression or unacceptable toxicity.

What Are the Treatments Tested in This Trial?

Interventions

• CDX-1140
• CDX-301
• PLD Chemotherapy

Trial Overview The study tests if combining immunotherapy drugs CDX-301 and CDX-1140 with standard chemotherapy PLD is safe and effective against this type of breast cancer. It aims to find the right dose and schedule for these drugs while also observing how they affect the body's immune response to cancer.

How Is the Trial Designed?

Group I: Cohort C Experimental Treatment 3 Interventions

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.

Group II: Cohort A Experimental Treatment 3 Interventions

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.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Celldex Therapeutics

Industry Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Published Research Related to This Trial

The study developed doxorubicin-loaded platelet decoys (PD@Dox) that not only deliver chemotherapy but also induce immunogenic cell death (ICD) in triple-negative breast cancer (TNBC), enhancing the immune response against tumors.

Combining PD@Dox with PD-1 antibody therapy significantly improved treatment efficacy by blocking tumor immune escape and activating T cells, suggesting a promising new approach for TNBC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin-Loaded Platelet Decoys for Enhanced Chemoimmunotherapy Against Triple-Negative Breast Cancer in Mice Model. Dong, H., Gao, M., Lu, L., et al.[2023]

The maximum tolerated dose (MTD) for pegylated liposomal doxorubicin was determined to be 10 mg/m² per week when combined with paclitaxel at 80 mg/m² per week, based on a study involving 19 patients with advanced solid tumors.

The treatment was generally well tolerated, with manageable dose-limiting toxicities including grade 3 neutropenia and diarrhea, and no significant cardiac toxicity observed, suggesting it is safe for further evaluation in sensitive tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of weekly paclitaxel and liposomal doxorubicin in patients with advanced solid tumours. Androulakis, N., Kouroussis, C., Mavroudis, D., et al.[2019]

Stealth liposomal doxorubicin (Caelyx, Doxil) shows promise as a treatment for breast cancer, leveraging its unique liposomal formulation to improve drug delivery and efficacy.

The liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics and reduces toxicity compared to traditional non-liposomal doxorubicin, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. Ranson, MR., Cheeseman, S., White, S., et al.[2019]

The ALICE trial demonstrated that adding atezolizumab (an anti-PD-L1 immune checkpoint inhibitor) to chemotherapy improved progression-free survival in patients with metastatic triple-negative breast cancer, with a median of 4.3 months compared to 3.5 months for those receiving placebo.

The treatment was generally well-tolerated, with 18% of patients in the atezo-chemo group experiencing adverse events leading to drug discontinuation, compared to 7% in the placebo group, suggesting that atezolizumab can be safely combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial. Røssevold, AH., Andresen, NK., Bjerre, CA., et al.[2023]

The combination of doxorubicin (DOX) with ginsenoside Rg3-loaded nanoparticles significantly enhanced immunogenic cell death (ICD) in triple-negative breast cancer (TNBC), leading to a stronger immune response compared to DOX alone.

Using a thermo-sensitive hydrogel to co-deliver DOX and Rg3-PNPs, along with PD-L1 immunotherapy, effectively transformed nonimmunogenic tumors into immunogenic ones, resulting in substantial antitumor effects and improved recruitment of memory T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ginsenoside Rg3 nanoparticles with permeation enhancing based chitosan derivatives were encapsulated with doxorubicin by thermosensitive hydrogel and anti-cancer evaluation of peritumoral hydrogel injection combined with PD-L1 antibody. Wu, H., Wei, G., Luo, L., et al.[2022]

In a study of 42 patients receiving cumulative doses of pegylated liposomal doxorubicin (doxil) exceeding 500 mg/m2, none developed clinical congestive heart failure, indicating a favorable safety profile for higher doses compared to traditional doxorubicin.

While five patients experienced a drop in left ventricular ejection fraction (LVEF), the overall risk of cardiomyopathy appears significantly lower with doxil, even in patients previously treated with doxorubicin, suggesting that doxil may be a safer option for patients with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. Safra, T., Muggia, F., Jeffers, S., et al.[2022]

In a phase I study involving 26 patients with advanced solid tumors, the combination of pegylated liposomal doxorubicin (Caelyx) and paclitaxel was found to be feasible, with a maximum tolerated dose established at 15 mg/m2 for Caelyx and 115 mg/m2 for paclitaxel, administered every two weeks.

The treatment regimen showed acceptable toxicity levels, with mild hematologic side effects and no significant cardiotoxicity, while achieving a complete response in one patient and partial responses in four, particularly among breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. Mavroudis, D., Kouroussis, Ch., Kakolyris, S., et al.[2018]

In a phase II study involving 34 patients with metastatic breast cancer, the combination of paclitaxel and liposomal doxorubicin was effective in 73% of patients, showing a high response rate with 7 complete and 18 partial responses.

The treatment had a moderate toxicity profile, with only a small number of severe side effects reported, including 2 toxic deaths (6%), indicating that while effective, careful monitoring for serious adverse effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. Vorobiof, DA., Rapoport, BL., Chasen, MR., et al.[2015]

In a study of 27 metastatic breast cancer patients treated with pegylated liposomal doxorubicin (PLD) and vinorelbine, there were no treatment interruptions or cardiac toxicity, highlighting the cardiac safety of PLD compared to traditional doxorubicin.

The combination treatment showed a median progression-free survival of 5.3 months and an overall clinical benefit rate of 55.5%, indicating its efficacy in patients previously treated with anthracycline-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin (Caelyx®) and oral vinorelbine in first-line metastatic breast cancer patients previously treated with anthracyclines. Livi, L., Meattini, I., Scotti, V., et al.[2018]

Triple-negative breast cancer is a diverse and aggressive type of cancer, and while molecular characterization isn't standard practice, it can help in understanding the disease better and predicting outcomes.

Recent advances in treatment options include neoadjuvant platinum-based chemotherapy and targeted therapies for patients with BRCA mutations, which may improve outcomes in various stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the systemic treatment of triple-negative breast cancer. Lebert, JM., Lester, R., Powell, E., et al.[2023]

In a study of 162 patients with stages I-III Triple-negative breast cancer (TNBC), pegylated liposomal doxorubicin (PLD) showed similar overall survival (OS) and relapse-free survival (RFS) rates compared to conventional chemotherapy, indicating its efficacy as an alternative treatment.

PLD-based chemotherapy resulted in a lower incidence of severe neutropenia (25% vs. 41.6%) but a higher incidence of hand-foot syndrome (16.3% vs. 4.4%), suggesting a different safety profile compared to traditional anthracycline treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. Lien, MY., Liu, LC., Wang, HC., et al.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1126

Phase 1 pilot study with dose expansion of chemotherapy ... This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05029999

Study Details | NCT05029999 | CD40 Agonist, Flt3 Ligand ... 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 ...

3. aacrjournals.org aacrjournals.org/cancerres/article/83/5_Supplement/OT2-17-01/717518/Abstract-OT2-17-01-Phase-1-trial-of-anthracycline

Abstract OT2-17-01: Phase 1 trial of anthracycline ... This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with ...

4. onclive.com onclive.com/view/cdx-1140-plus-pembrolizumab-elicits-responses-in-pd-1-pd-l1-resistant-solid-tumors

CDX-1140 Plus Pembrolizumab Elicits Responses in PD-1/ ... The utilization of the anti-CD40 agonist, CDX-1140, in combination with pembrolizumab was generally well tolerated and demonstrated preliminary efficacy.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12289982/

The untapped potential of radiation and immunotherapy for ... Immune checkpoint inhibition (ICI) is an established treatment for triple-negative BC (TNBC) in combination with chemotherapy. While ICI has not ...