Avelumab Combinations for Triple Negative Breast Cancer (InCITe Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Hope Rugo, MD
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies how well the combination of avelumab with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan works in treating patients with triple negative breast cancer that is stage IV or is not able to be removed by surgery (unresectable) and has come back (recurrent). Immunotherapy with checkpoint inhibitors like avelumab require activation of the patient's immune system.
This trial includes a two week induction or lead-in of medications that can stimulate the immune system. It is our hope that this induction will improve the response to immunotherapy with avelumab. One treatment, sacituzumab Govitecan, is a monoclonal antibody called sacituzumab linked to a chemotherapy drug called SN-38. Sacituzumab govitecan is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as Tumor-associated calcium signal transducer 2 (TROP2) receptors, and delivers SN-38 to kill them. Another treatment, liposomal doxorubicin, is a form of the anticancer drug doxorubicin that is contained in very tiny, fat-like particles. It may have fewer side effects and work better than doxorubicin, and may enhance factors associated with immune response. The third medication is called binimetinib, which may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth, and may help activate the immune system. It is not yet known whether giving avelumab in combination with liposomal doxorubicin with or without binimetinib, or the combination of avelumab with sacituzumab govitecan will work better in treating patients with triple negative breast cancer.
How is the drug combination of Avelumab, Liposomal Doxorubicin, and Sacituzumab Govitecan unique for treating triple-negative breast cancer?
This drug combination is unique because it includes sacituzumab govitecan, an antibody-drug conjugate that targets a specific protein (Trop-2) on cancer cells, delivering a potent chemotherapy agent (SN-38) directly to the tumor, which can improve survival outcomes compared to standard chemotherapy.
12356Is sacituzumab govitecan safe for humans?
Sacituzumab govitecan has been shown to have a manageable safety profile in clinical trials for metastatic triple-negative breast cancer, with common side effects including nausea, neutropenia (low white blood cell count), and diarrhea.
23458What data supports the effectiveness of the drug Sacituzumab Govitecan for treating triple-negative breast cancer?
Research shows that Sacituzumab Govitecan helps patients with metastatic triple-negative breast cancer live longer and shrink tumors more effectively than standard chemotherapy. However, it may cause more side effects like low white blood cell counts and diarrhea.
23567Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, there are specific 'washout' periods (time without taking certain medications) required for prior therapies, such as chemotherapy and radiation, before starting the trial. It's best to discuss your current medications with the study team to understand any necessary adjustments.
Eligibility Criteria
This trial is for adults with stage IV or unresectable, recurrent triple negative breast cancer. Participants must be over 18, have an ECOG status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but ambulatory), and adequate organ function. They should not have had more than two chemotherapy treatments in the metastatic setting nor more than one prior checkpoint inhibitor therapy.Inclusion Criteria
My breast cancer is at stage IV or has come back in the same area and cannot be surgically removed.
I am 18 years old or older.
I am willing to undergo a biopsy for the study.
My cancer's PD-L1 status is known.
I am fully active or have some restrictions but can still care for myself.
Exclusion Criteria
I have received an organ or stem cell transplant.
I have had pancreatitis, eye vein blockage, or take blood thinners.
I do not have significant infections like HIV or hepatitis.
I don't have lasting side effects from past treatments, severe allergies to monoclonal antibodies, or a history of severe allergic reactions.
I do not have severe lung problems, uncontrolled heart or blood pressure issues.
I have had more than one treatment with checkpoint inhibitors for my advanced cancer.
I have had more than 2 chemotherapy treatments for my cancer after it spread.
I have brain metastases but meet certain criteria for this trial.
I have an autoimmune disease that might worsen with immune-stimulating treatments.
I have a muscle disorder that causes high levels of creatine kinase.
I have previously been treated with sacituzumab govitecan.
Participant Groups
The study tests avelumab combined with liposomal doxorubicin, with/without binimetinib, or paired with sacituzumab govitecan to see which works best for treating patients. Avelumab is an immunotherapy drug; sacituzumab govitecan targets tumor cells directly; liposomal doxorubicin is a chemo drug that may reduce side effects; binimetinib blocks enzymes needed for cell growth.
6Treatment groups
Experimental Treatment
Group I: CLOSED TO ENROLLMENT: Arm III (utomilumab, avelumab)Experimental Treatment2 Interventions
Patients will receive a 15-day lead-in of utomilumab, followed by utomilumab IV over 60 minutes every 4 weeks and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group II: CLOSED TO ENROLLMENT: Arm II (anti-OX40 antibody PF-04518600, avelumab)Experimental Treatment2 Interventions
Patients will receive a 15-day lead-in of anti-OX40 antibody PF-04518600, followed by anti-OX40 antibody PF-04518600 IV over 60 minutes and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group III: CLOSED TO ENROLLMENT: Arm I (binimetinib, avelumab)Experimental Treatment2 Interventions
Patients will receive a 15-day lead-in of binimetinib, followed by binimetinib PO BID and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group IV: Arm C (avelumab, liposomal doxorubicin)Experimental Treatment2 Interventions
Patients will receive a 15-day lead-in of liposomal doxorubicin, followed by liposomal doxorubicin on Day 1 and 10mg/kg avelumab over 60 minutes on Day 1 and Day 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Group V: Arm B (avelumab, sacituzumab govitecan)Experimental Treatment2 Interventions
Patients will receive a 15-day lead-in of sacituzumab govitecan given on day -15, followed by sacituzumab govitecan day 8 and day 15 of Cycle (C) 1; day 1,8, and 21 of C2; day 1, 15 and 21 of C3; day 8 and 15 of C4, and schedule continues with two weeks on, one week off for 21-day cycles. Patients also receive 10mg/kg avelumab over 60 minutes on day 1 and day 15 of each 28 day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity.
Group VI: Arm A (avelumab, binimetinib, liposomal doxorubicin)Experimental Treatment3 Interventions
Patients receive a 15 day lead-in of binimetinib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then receive binimetinib PO BID on days 1-28, avelumab intravenously (IV) over 60 minutes on days 1 and 15, and liposomal doxorubicin IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Avelumab is already approved in European Union, United States, Japan for the following indications:
🇪🇺 Approved in European Union as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
🇺🇸 Approved in United States as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
🇯🇵 Approved in Japan as Bavencio for:
- Merkel cell carcinoma
- Renal cell carcinoma
- Urothelial carcinoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Duke Cancer InstituteDurham, NC
University of Chicago Medicine Comprehensive Cancer CenterEvergreen Park, IL
Georgetown UniversityWashington, United States
Dana-Farber Cancer InstituteBoston, MA
More Trial Locations
Loading ...
Who is running the clinical trial?
Hope Rugo, MDLead Sponsor
Translational Breast Cancer Research ConsortiumCollaborator
Hoosier Cancer Research NetworkCollaborator
PfizerIndustry Sponsor
Breast Cancer Research FoundationCollaborator
Gilead SciencesIndustry Sponsor
Array BioPharmaIndustry Sponsor
Johns Hopkins UniversityCollaborator
References
An ADC for Triple-Negative Breast Cancer. [2018]A phase II study indicates that sacituzumab govitecan (IMMU-132), a Trop-2-specific antibody linked to the irinotecan metabolite SN-38, prolongs the progression-free survival of patients with advanced triple-negative breast cancer. IMMU-132 is well tolerated, causing fewer and more manageable side effects than irinotecan.
Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors.
ADC Could Benefit Some with Breast Cancer. [2020]Results from a phase I/II trial suggest that an antibody-drug conjugate, sacituzumab govitecan, is active against refractory, metastatic triple-negative breast cancer. A phase III trial is under way to compare its safety and efficacy with that of standard chemotherapy.
Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer. [2020]Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan. Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for 'sacituzumab govitecan' and 'clinical trial'. Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.
Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.
Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. [2022]The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes.
A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer. [2021]Sacituzumab Govitecan (also known by the brand name TRODELVY®) is a new and available treatment for metastatic triple-negative breast cancer, or mTNBC for short. Metastatic breast cancer means the breast cancer has spread to other parts of the body. Triple negative means the breast cancer does not have 3 common proteins on the cell surface called receptors. This is a summary of the ASCENT study, published in the New England Journal of Medicine in April 2021. This study compared Sacituzumab Govitecan with standard chemotherapy. Chemotherapy is a treatment that kills cancer cells or stops them from dividing. 529 people with mTNBC took part in the study across 7 countries. All who took part had already received 2 previous chemotherapies, which stopped working for their cancer. The study showed that patients who took Sacituzumab Govitecan lived longer than those who took a different chemotherapy while on the study. Tumors shrank in more patients who took Sacituzumab Govitecan than in patients who took chemotherapy. In general, patients who took Sacituzumab Govitecan experienced more side effects. This included low levels of a type of white blood cell known as neutrophils (neutropenia) and loose or watery stool (diarrhea). Use of supportive care lessened these side effects. This summary also includes insights and perspectives from 2 breast cancer patient advocates. ClinicalTrials.gov NCT number: NCT02574455. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here.
The European Medicines Agency review of sacituzumab govitecan for the treatment of triple-negative breast cancer. [2022]Sacituzumab govitecan (SG) is an antineoplastic agent which combines a humanized monoclonal antibody binding to trophoblast cell surface antigen-2 (Trop-2)-expressing cancer cells, linked with cytotoxic moiety SN-38 (govitecan) with topoisomerase I inhibitor action. On 22 November 2021, a marketing authorization valid through the European Union (EU) was issued under the European Medicines Agency (EMA)'s accelerated assessment program for SG as monotherapy for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. The assessment was based on results from an open-label, randomized, phase III trial to evaluate the safety, tolerability, pharmacokinetics and efficacy of SG versus treatment of physician's choice (TPC) in patients with mTNBC who received at least two prior treatments including at least one of them for advanced disease. The efficacy results in the overall population, based on mature data, showed a statistically significant improvement of SG over TPC in progression-free survival (PFS) and overall survival (OS). The median PFS was 4.8 months versus 1.7 months [hazard ratio (HR) = 0.43, n = 529; 95% CI 0.35-0.54; P 30%) side effects of SG were diarrhea, neutropenia, nausea, fatigue, alopecia, anemia, constipation and vomiting. The aim of this manuscript is to summarize the scientific review of the application leading to regulatory approval in the EU.