Trial Summary
What is the purpose of this trial?This trial tests a new combination of two immune-boosting drugs and a chemotherapy drug in patients with hard-to-treat breast cancer. The goal is to see if this combination is safe and effective at controlling the cancer.
Is the drug CDX-1140, CDX-301, PLD Chemotherapy a promising treatment for triple-negative breast cancer?Yes, the drug CDX-1140, CDX-301, PLD Chemotherapy is promising for triple-negative breast cancer because it combines chemotherapy with immune therapy, which has shown potential in improving cancer treatment. PLD, a form of chemotherapy, is effective and less toxic, and combining it with immune-stimulating drugs like CDX-1140 and CDX-301 could enhance the body's ability to fight cancer.7891011
What safety data is available for the treatment of triple negative breast cancer with immunotherapy and chemotherapy?The safety data for the treatment involving pegylated liposomal doxorubicin (Caelyx/Doxil) and paclitaxel shows a moderate toxicity profile. In a phase II study, grade 3/4 toxicities were observed in a small number of patients, with two toxic deaths reported. Another study indicated reduced cardiotoxicity with pegylated liposomal doxorubicin, even at high doses. Phase I studies identified dose-limiting toxicities such as neutropenia and diarrhea, but overall, the combination was well-tolerated with manageable side effects. These studies support the cardiac safety and efficacy of pegylated liposomal doxorubicin in combination with other agents for breast cancer treatment.13456
What data supports the idea that Immunotherapy + Chemotherapy for Triple Negative Breast Cancer is an effective treatment?The available research shows that combining immunotherapy with chemotherapy, specifically using drugs like pegylated liposomal doxorubicin (PLD) and atezolizumab, can be effective for treating triple-negative breast cancer. For example, in the ALICE trial, patients who received this combination had a longer time before their cancer progressed compared to those who received chemotherapy alone. This suggests that the combination treatment might help control the disease better than chemotherapy by itself.2791011
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, there are restrictions on certain treatments before starting the trial, such as no chemotherapy or antibody drug conjugates within 21 days, no kinase inhibitors within 2 weeks, and no immunosuppressive medications within 4 weeks prior to the trial. It's best to discuss your specific medications with the trial team.
Eligibility Criteria
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 is PD-L1 negative and I can't have standard FDA-approved chemotherapy.
I am 18 years old or older.
My breast cancer is advanced and cannot be removed by surgery.
I am able to get out of my bed or chair and move around.
Any side effects from my previous cancer treatments have mostly gone away.
Exclusion Criteria
I haven't taken any kinase inhibitors in the last 2 weeks.
I have received a high dose of a specific chemotherapy drug.
I do not have an active infection needing treatment, HIV, or hepatitis B/C.
I have had or currently have lung inflammation not caused by an infection.
I haven't had chemotherapy in the last 3 weeks or within its half-life period before starting the study treatment.
I have had acute myeloid leukemia or my tumor has a Flt3 mutation.
I am not pregnant or nursing, and I have a negative pregnancy test.
I have brain metastases that haven't been treated.
I haven't taken immunosuppressants or steroids in the last 4 weeks.
I have been treated with anthracycline for cancer that has spread.
I have not been treated with anti-CD40 antibody or rhuFlt3L products.
I have not had major surgery in the last 4 weeks.
I haven't had any type of radiation therapy in the last 2 to 8 weeks.
I've been cancer-free for 3 years, except for minor skin cancers or in situ cancers.
My cancer got worse on anthracycline therapy or within 6 months after stopping it.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Group I: Cohort CExperimental Treatment3 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 AExperimental Treatment3 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.
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of North CarolinaChapel Hill, NC
University of Chicago Comprehensive Cancer CenterChicago, IL
Texas Oncology, P.A.Dallas, TX
UT Southwestern Medical CenterDallas, TX
More Trial Locations
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Who is running the clinical trial?
University of Texas Southwestern Medical CenterLead Sponsor
Celldex TherapeuticsIndustry Sponsor
Gateway for Cancer ResearchCollaborator
References
Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m2. [2022]The indications for pegylated liposomal doxorubicin (doxil) are expanding. We, therefore, wished to assess the safety of delivering doses exceeding 500 mg/m2 of doxil to patients with solid tumors.
Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. [2019]Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.
Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx) administered every 2 weeks in patients with advanced solid tumors. [2018]Paclitaxel and doxorubicin are among the most active chemotherapeutic agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a more favorable pharmacokinetic and toxicity profile than the free drug. We conducted a phase I study to determine the maximum tolerated doses (MTD) and the dose limiting toxicities (DLT) of the combination administered every 2 weeks in patients with advanced solid tumors.
Phase I study of weekly paclitaxel and liposomal doxorubicin in patients with advanced solid tumours. [2019]The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities (DLT) of a weekly administration of paclitaxel and pegylated liposomal doxorubicin (Caelyx; Schering Plough Pharmaceutical) in patients with advanced solid tumours. 19 pretreated patients with solid tumours received escalated doses of pegylated liposomal doxorubicin (6-12 mg/m(2)) as a 1-h intravenous (i.v.) infusion followed by a fixed dose of paclitaxel (80 mg/m(2)) weekly for 4 consecutive weeks in cycles of 6 weeks. DLT was defined as grade 4 neutropenia or thrombocytopenia, febrile neutropenia, grades 3 or 4 non-haematological toxicity or treatment delay due to unresolved toxicity during cycle 1. The MTD was reached at the dose of pegylated liposomal doxorubicin of 10 mg/m(2)/week and paclitaxel of 80 mg/m(2)/week. The DLTs were treatment delay due to grade 3 neutropenia and grade 3 diarrhoea. A total of 55 chemotherapy cycles were administered, and grades 3-4 neutropenia occurred in seven cycles (13%); the non-haematological toxicity was mild with grades 2/3 diarrhoea occurring in 4 (7%), grades 2-4 asthenia in 11 (20%) and grade 2 mucositis in 7 (13%) cycles. There was no case with more than a 10% LVEF decrease after a median of 3 (range 2-6) administered cycles/patients. One patient with breast cancer and 1 with ovarian cancer experienced a major partial response. The weekly administration of pegylated liposomal doxorubicin at the dose of 10 mg/m(2) in combination with paclitaxel at the dose of 80 mg/m(2) for 4 consecutive weeks, in cycles of 6 weeks which represent the recommended doses for further phase II studies, is a well tolerated regimen, which merits further evaluation in tumours known to be sensitive to taxanes and/or anthracyclines.
First line therapy with paclitaxel (Taxol) and pegylated liposomal doxorubicin (Caelyx) in patients with metastatic breast cancer: a multicentre phase II study. [2015]The aim of this multicentric phase II study was to investigate the efficacy and toxicity of a combination of chemotherapy containing paclitaxel (Taxol) and a novel compound, a liposomal encapsulated doxorubicin (Caelyx), as first line therapy for patients with metastatic breast cancer. Thirty-four patients with advanced breast cancer were treated with a combination of paclitaxel 175 mg/m2 and liposomal doxorubicin 30 mg/m2, every 3 weeks. The combination chemotherapy was effective in 73% of the patients (ITT) (95% CI 55-86%) (7 complete and 18 partial responses). Grade 3/4 toxicities were documented in a small number of patients. Two toxic deaths (6%) were documented, one a hepatorenal failure and another a febrile neutropenia. One patient experienced pulmonary embolism but continued on treatment after appropriate therapy. The combination of paclitaxel and liposomal encapsulated doxorubicin induces a high and durable response rate with a moderate toxicity profile.
Pegylated liposomal doxorubicin (Caelyx®) and oral vinorelbine in first-line metastatic breast cancer patients previously treated with anthracyclines. [2018]Doxorubicin is highly effective and widely used in breast cancer; however, its use is limited by cardiotoxicity related to its cumulative dose. In previous studies, pegylated liposomal doxorubicin (PLD) has shown an acceptable toxicity profile with minimal cardiotoxicity. Between June 2006 and October 2009, 27 metastatic breast cancer patients were treated with first-line PLD and vinorelbine at the University of Florence, Radiotherapy Unit. PLD (30 mg/m²) was administered on day 1, and oral vinorelbine (60 mg/m²) was administered on days 1 and 8 of a 4-week cycle. All patients were previously treated with anthracycline-based adjuvant chemotherapy. Median age was 52 years (range 38-69) and median time to metastasis was 78.5 months. There were no treatment interruptions or discontinuation for cardiac toxicity and no treatment-related deaths. Grade 3 hematological toxicity was observed in 18.6% of patients, and 3.7% had grade 3 non-hematological adverse events. With a median follow-up of 13.2 months (range 3-33), median response duration was 6.1 months, and median PFS was 5.3 months. The overall clinical benefit rate was 55.5%. Our experience adds to evidence supporting the activity and cardiac safety of PLD and vinorelbine in metastatic breast cancer patients previously treated with anthracycline-based adjuvant chemotherapy.
Safety and efficacy of pegylated liposomal doxorubicin-based adjuvant chemotherapy in patients with stage I-III triple-negative breast cancer. [2018]Pegylated liposomal doxorubicin (PLD) has been proven to be an effective antitumor drug for metastatic breast cancer, with less toxicity than conventional anthracycline. Our objective was to evaluate the efficacy and safety of PLD-based adjuvant chemotherapy compared to conventional chemotherapy for patients with stages I-III Triple-negative breast cancer (TNBC).
Advances in the systemic treatment of triple-negative breast cancer. [2023]Triple-negative breast cancer constitutes a heterogeneous group of malignancies that are often aggressive and associated with a poor prognosis. Molecular characterization, while not a standard of care, can further subtype triple-negative breast cancer and provide insight into prognostication and behaviour. Optimal chemotherapy regimens have yet to be established; however, there have been advances in the systemic treatment of triple-negative breast cancer in the neoadjuvant, adjuvant, and metastatic settings. In this review, we discuss evidence for the potential benefit of neoadjuvant platinum-based chemotherapy, adjuvant combination chemotherapy with weekly paclitaxel, and BRCA mutation-directed therapy in the metastatic setting. The role for adjuvant capecitabine in patients who do not achieve a pathologic complete response with neoadjuvant chemotherapy is reviewed. Future directions and data concerning novel targeted agents are reviewed, including the most recent data on parp [poly (adp-ribose) polymerase] inhibitors, antiandrogen agents, and immunotherapy.
Atezolizumab plus anthracycline-based chemotherapy in metastatic triple-negative breast cancer: the randomized, double-blind phase 2b ALICE trial. [2023]Immune checkpoint inhibitors have shown efficacy against metastatic triple-negative breast cancer (mTNBC) but only for PD-L1positive disease. The randomized, placebo-controlled ALICE trial ( NCT03164993 , 24 May 2017) evaluated the addition of atezolizumab (anti-PD-L1) to immune-stimulating chemotherapy in mTNBC. Patients received pegylated liposomal doxorubicin (PLD) and low-dose cyclophosphamide in combination with atezolizumab (atezo-chemo; n = 40) or placebo (placebo-chemo; n = 28). Primary endpoints were descriptive assessment of progression-free survival in the per-protocol population (>3 atezolizumab and >2 PLD doses; n = 59) and safety in the full analysis set (FAS; all patients starting therapy; n = 68). Adverse events leading to drug discontinuation occurred in 18% of patients in the atezo-chemo arm (7/40) and in 7% of patients in the placebo-chemo arm (2/28). Improvement in progression-free survival was indicated in the atezo-chemo arm in the per-protocol population (median 4.3 months versus 3.5 months; hazard ratio (HR) = 0.57; 95% confidence interval (CI) 0.33-0.99; log-rank P = 0.047) and in the FAS (HR = 0.56; 95% CI 0.33-0.95; P = 0.033). A numerical advantage was observed for both the PD-L1positive (n = 27; HR = 0.65; 95% CI 0.27-1.54) and PD-L1negative subgroups (n = 31; HR = 0.57, 95% CI 0.27-1.21). The progression-free proportion after 15 months was 14.7% (5/34; 95% CI 6.4-30.1%) in the atezo-chemo arm versus 0% in the placebo-chemo arm. The addition of atezolizumab to PLD/cyclophosphamide was tolerable with an indication of clinical benefit, and the findings warrant further investigation of PD1/PD-L1 blockers in combination with immunomodulatory chemotherapy.
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. [2022]Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear "cold" tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.
Doxorubicin-Loaded Platelet Decoys for Enhanced Chemoimmunotherapy Against Triple-Negative Breast Cancer in Mice Model. [2023]Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis. Current single-agent checkpoint therapy has limited effectiveness in TNBC patients. In this study, we developed doxorubicin-loaded platelet decoys (PD@Dox) for chemotherapy and induction of tumor immunogenic cell death (ICD). By combining PD-1 antibody, PD@Dox has the potential to enhance tumor therapy through chemoimmunotherapy in vivo.