Clinical trials

Claudin 18.2 or CLDN18.2 is a protein found on cells in the digestive system. It is also found in some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a type of immune cell called a T cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with gastric cancer (also known as stomach cancer) or gastroesophageal junction cancer (GEJ cancer). GEJ is where the tube that carries food (esophagus) joins the stomach. This study is for people with gastric or GEJ cancer that has spread nearby (locally advanced) and is not removable by surgery (unresectable), or has spread to other parts of the body (metastatic). It is for those whose cancer is human epidermal growth factor receptor 2 (HER2)-negative and CLDN18.2-positive. HER2-negative means the cancer does not have extra HER2 protein, so medicines that target HER2 do not work and are therefore not used. CLDN18.2-positive means people have a certain amount of CLDN18.2 proteins on their cancer cells. In this study, researchers want to learn if ASP2138 given together with standard treatments (chemotherapy and pembrolizumab) help people with HER2-negative and CLDN18.2-positive gastric or GEJ cancer. The main aim is to learn how long people who are given ASP2138 with chemotherapy and pembrolizumab live without their cancer getting worse, compared with placebo given with chemotherapy with or without pembrolizumab, and if they live for longer. Placebo looks like the study treatment but does not have any medicine in it. The main aim of this study is to check how well ASP2138 works when given together with chemotherapy and pembrolizumab compared with placebo plus chemotherapy with or without pembrolizumab. People aged 18 years or older with locally advanced unresectable or metastatic gastric or GEJ cancer can take part. Their tumor should be HER2-negative and CLDN18.2-positive. The study doctors will check people for any health conditions that can exclude them from taking part, interfere with the study procedures, or pose an unacceptable risk. This is a double-blind study. That means the people and the study doctors will not know who will receive which treatment. People will be assigned to one of 2 treatment groups by chance: Group A: People will receive ASP2138 along with chemotherapy and pembrolizumab. Group B: People will receive placebo along with chemotherapy, with or without pembrolizumab. People will keep receiving treatment until their cancer gets worse, they have medical problems that require stopping treatment, or a study rule says they must stop. There will be regular safety checks. People will continue to have scans of their tumor until their cancer becomes worse.

The purpose of this study is to assess the efficacy and safety of cevostamab in combination with pomalidomide and dexamethasone (CevosPd) versus standard of care (SOC) in participants with multiple myeloma (MM) who have received one to three prior lines of therapy and have been exposed to an anti-CD38 monoclonal antibody (mAb) and lenalidomide.

This phase III trial compares standard of care hormone therapy plus ribociclib to chemotherapy followed by hormone therapy plus ribociclib for the treatment of patients with high anatomic stage breast cancer with low risk of the cancer returning (low risk recurrence). Ribociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy, with letrozole, anastrozole or exemestane, lowers the amount of estrogen made by the body. This may help stop the growth of tumor cells that need estrogen to grow. Chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Hormone therapy plus ribociclib may work as well as chemotherapy followed by hormone therapy plus ribociclib for the treatment of high anatomic stage breast cancer with low recurrence risk.

This is a Phase Ⅲ, randomized, open-label, Sponsor-blinded, 3-arm, global, multicenter study assessing the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm.

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

The purpose of this multicenter, open label trial (NAPISTAR 1-01) is to evaluate the safety/tolerability, pharmacokinetics and preliminary efficacy of TUB-040 and to find the best dose of TUB-040 in participants with ovarian cancer and Non Small Cell Lung Cancer. TUB-040 is an antibody-drug-conjugate which delivers a topoisomerase I inhibitor to tumor cells which overexpress the target NaPi2b. The study consists of three parts: In dose escalation, ovarian cancer participants and lung cancer participants receive increasing doses of TUB-040 until the maximal tolerated dose is found. In dose optimization, at least two doses are compared with each other to determine which dose is optimal for participants. In dose expansion, a single dose will be used in a larger number of participants. TUB-040 is given IV every 3 weeks until the disease progresses or the participants has to stop due to side effects.

This phase II ComboMATCH treatment trial compares the effect of neratinib to the combination of neratinib and palbociclib in treating patients with HER2 positive solid tumors. Neratinib and palbociclib are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving neratinib and palbociclib in combination may shrink or stabilize cancers that over-express a specific biomarker called HER2.

This pilot trial assesses the effect of the combination of blinatumomab with dasatinib or imatinib and standard chemotherapy for treating patients with Philadelphia chromosome positive (Ph+) or ABL-class Philadelphia chromosome-like (Ph-like) B-Cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is a bispecific antibody that binds to two different proteins-one on the surface of cancer cells and one on the surface of cells in the immune system. An antibody is a protein made by the immune system to help fight infections and other harmful processes/cells/molecules. Blinatumomab may bind to the cancer cell and a T cell (which plays a key role in the immune system's fighting response) at the same time. Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib and imatinib are in a class of medications called tyrosine kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Giving blinatumomab and dasatinib or imatinib in combination with standard chemotherapy may work better in treating patients with Ph+ or Ph-like ABL-class B-ALL than dasatinib or imatinib with chemotherapy.

This phase II trial tests effects of nivolumab in combination with chemotherapy drugs prior to radiation therapy patients with nasopharyngeal carcinoma (NPC). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Researchers want to find out what effects, good and/or bad, adding nivolumab to chemotherapy has on patients with newly diagnosed NPC. In addition, they want to find out if children with NPC may be treated with less radiation therapy and whether this decreases the side effects of therapy.

The primary objectives are to compare progression-free survival (PFS) and overall survival (OS) in participants who receive sotorasib with platinum doublet chemotherapy versus participants who receive pembrolizumab with platinum doublet chemotherapy.

This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a protein on a type of immune cell called a T-cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with stomach cancer, gastroesophageal junction cancer (GEJ cancer) or pancreatic cancer. GEJ is where the tube that carries food (esophagus) joins the stomach. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. In this study, ASP2138 will either be given by itself, or given together with standard treatments for gastric, GEJ and pancreatic cancer. Pembrolizumab and mFOLFOX6, and ramucirumab and paclitaxel are standard treatments for gastric and GEJ cancer. mFOLFIRINOX is a standard treatment for pancreatic cancer. This information will help find a suitable dose of ASP2138 given by itself and together with the standard cancer treatments and to check for potential medical problems from the treatments. The main aims of the study are: * To check the safety of ASP2138 and how well people can tolerate medical problems during the study. * To find a suitable dose of ASP2138 to be used later in the study. * These are done for ASP2138 given by itself and when given together with the standard cancer treatments. Adults 18 years or older with stomach cancer, GEJ cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. There should also be the CLDN18.2 marker in a tumor sample. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers, have specific infections, have a condition such as hemophagocytic lymphohistiocytosis (HLH) which is when the body over-reacts to a "trigger" such as infection, or have a specific heart condition ("New York Heart Association Class III or IV"). Phase 1: Lower to higher doses of ASP2138 * ASP2138 is either given through a vein (intravenous infusion) or just under the skin (subcutaneous injection). * Different small groups are given lower to higher doses of ASAP2138. * ASP2138 is either given by itself, or given with 1 of 3 standard treatments: * Pembrolizumab and mFOLFOX6 (first treatment for gastric GEJ cancer) * Ramacirumab and paclitaxel (Second treatment for gastric or GEJ cancer) * ASP2138 with mFOLFIRINOX (first treatment for pancreatic cancer) Phase 1b: doses of ASP2138 worked out from Phase 1 * ASP2138 is either given through a vein or just under the skin. This depends on the findings from Phase 1. * People with gastric cancer, GEJ cancer or pancreatic cancer are given doses of ASP2138, worked out from Phase 1. * This includes doses of ASP2138 given by itself and ASP2138 given with the standard cancer treatments. * The standard cancer treatments given depends on the type of cancer they have. End of treatment visit: This is 7 days after final dose of study treatment or if the study doctor decides to stop the person's treatment. People who have locally advanced unresectable pancreatic cancer will not receive ASP2138 by itself.

This phase III trial tests whether adding trastuzumab and hyaluronidase-oysk (Herceptin Hylecta \[TM\]) or pertuzumab, trastuzumab and hyaluronidase-zzxf (Phesgo \[TM\]) to the usual chemotherapy (paclitaxel and carboplatin) works to shrink tumors in patients with HER2 positive endometrial cancer. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to specific molecules (receptors) on the surface of tumor cells, known as HER2 receptors. When trastuzumab or pertuzumab attach to HER2 receptors, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Hyaluronidase is an endoglycosidase. It helps to keep pertuzumab and trastuzumab in the body longer, so that these medications will have a greater effect. Hyaluronidase also allows trastuzumab and trastuzumab/pertuzumab to be given by injection under the skin and shortens their administration time compared to trastuzumab or pertuzumab alone. Paclitaxel is a taxane and in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Giving Herceptin Hylecta or Phesgo in combination with paclitaxel and carboplatin may shrink the tumor and prevent the cancer from coming back in patients with HER2 positive endometrial cancer.

This phase III trial compares the effect of selumetinib versus the standard of care treatment with carboplatin and vincristine (CV) in treating patients with newly diagnosed or previously untreated low-grade glioma (LGG) that does not have a genetic abnormality called BRAFV600E mutation and is not associated with systemic neurofibromatosis type 1. Selumetinib works by blocking some of the enzymes needed for cell growth and may kill tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping tumor cells from growing and dividing and may kill them. The overall goal of this study is to see if selumetinib works just as well as the standard treatment of CV for patients with LGG. Another goal of this study is to compare the effects of selumetinib versus CV in subjects with LGG to find out which is better. Additionally, this trial will also examine if treatment with selumetinib improves the quality of life for subjects who take it.

This phase II trial studies how well inotuzumab ozogamicin and blinatumomab with or without ponatinib work in treating patients with CD22-positive B-lineage acute lymphoblastic leukemia that is newly diagnosed, has come back after a period of improvement (recurrent), or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug, called ozogamicin. Inotuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD22 receptors, and delivers ozogamicin to kill them. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Ponatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving inotuzumab ozogamicin and blinatumomab with or without ponatinib may be effective in treating patients with newly diagnosed, recurrent or refractory CD22 positive B-lineage acute lymphoblastic leukemia.

This study collects specimens from volunteers for use in studies by NIAID's Vaccine Research Center. A number of different types of specimens or samples can be collected, including blood, urine, body fluids or secretions, skin swabs, or skin biopsies. The samples are used for medical research, including the study of HIV, hepatitis, and other diseases; immune system responses, such as responses to vaccinations or infections; and for research on vaccine development. Blood samples may be collected either by ordinary blood drawing (phlebotomy) or by apheresis, a procedure for collecting a larger quantity of blood cells or plasma than would be possible through simple blood drawing. For this procedure, the participant lies on a recliner or couch. Blood is removed through a needle in the vein of one arm and spun in a machine that separates out the desired component (plasma or white blood cells). The remainder of the blood is returned either through the same needle or through a needle in the other arm. The procedure takes about 1 to 3 hours. Volunteers who are 18 years of age and older, including participants in other NIH research protocols, may be eligible. Individuals who have a condition that the research staff considers a reason not to make a sample donation will be excluded from the study. Participants may have only one sample collected or may be asked to undergo repetitive sample collection procedures, depending upon the requirements of the particular research project for which the samples are being collected. Each individual's enrollment is for a 1-year period, which can be extended.

The purpose of this trial is to evaluate how well petosemtamab in combination with chemotherapy works against colorectal cancer that has recurred after previous treatment and that cannot be safely removed by surgery or has spread to other parts of the body. Participants will receive either petosemtamab + doctor's choice of chemotherapy (mFOLFOX6 or FOLFIRI) or doctor's choice of standard-of-care (SOC) cetuximab or bevacizumab + chemotherapy (mFOLFOX6 or FOLFIRI). No participants will be given placebo. The treatment duration will be different for every participant. If a participant's cancer stays the same or gets better, and there are not any serious problems, participants can keep getting study treatment for as long as the study is open. Participants will be asked to attend 2 visits at the study clinic for each cycle (duration of cycle is 4 weeks). During visits, there will be various tests (such as blood draws) and procedures (such as imaging) to monitor whether the study treatment is safe and effective. The overall study duration (including screening, treatment, and follow-up) will be different for every participant.

The purpose of this study is to evaluate the efficacy and safety of tacabrutideg alone compared with pirtobrutinib in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had been previously treated with a covalent Bruton tyrosine kinase inhibitor (cBTKi).

Researchers are looking for new ways to treat people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or recurrent. * EC is a type of cancer that starts in the tissues inside the uterus (womb) * pMMR indicates that certain normal proteins are present in the cancer cells * Advanced means the cancer has spread locally or to other parts of the body (metastatic) and cannot be removed with surgery * Recurrent means the cancer came back after surgery Sacituzumab tirumotecan (also known as sac-TMT) and pembrolizumab are the study medicines. Sac-TMT is an antibody drug conjugate (ADC). An ADC attaches to specific targets on cancer cells and delivers treatment to destroy those cells. The goal of this study is to learn if people who receive sac-TMT with pembrolizumab live longer and without the cancer getting worse compared to people who receive pembrolizumab alone.

Non small cell lung carcinoma (NSCLC) is the most frequently occurring histologic subtype of lung cancer and is the leading cause of cancer-related deaths worldwide. The purpose of this study is to assess adverse events and change in disease activity when Telisotuzumab Adizutecan (ABBV-400) is given in combination with a programmed cell death receptor 1 (PD1) immune checkpoint inhibitor to adult participants to treat NSCLC. Telisotuzumab Adizutecan (ABBV-400) and budigalimab are investigational drugs being developed for the treatment of NSCLC. This study will be divided into two stages, with the first stage treating participants with several doses of telisotuzumab adizutecan in combination with budigalimab within the dose escalation regimen until the dose reached is tolerable and expected to be efficacious. In Stage 2 there will be 3 treatment groups. Two groups will receive pembrolizumab with different optimized doses of telisotuzumab adizutecan (to allow for the best dose to be studied in the future). One group will receive the standard of care (SOC) - pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed. Approximately 252 adult participants with NSCLC will be enrolled in the study in 132 sites worldwide. In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of Telisotuzumab Adizutecan in combination with budigalimab until the dose of Telisotuzumab Adizutecan reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive IV optimized doses of Telisotuzumab Adizutecan in combination with IV pembrolizumab, or IV SOC - pembrolizumab, pemetrexed, and investigator's choice of carboplatin or cisplatin, followed by pembrolizumab and pemetrexed. The study will run for a duration of approximately 33 months. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

The purpose of this study is to evaluate the effectiveness, safety, tolerability, drug levels and drug effects of ozanimod compared to fingolimod in children and adolescents with relapsing remitting multiple sclerosis (RRMS).

This phase II MyeloMATCH treatment trial compares the usual treatment of azacitidine and venetoclax to the combination treatment of azacitidine, venetoclax and gilteritinib in treating older and unfit patients with acute myeloid leukemia and FLT3 mutations. Azacitidine is a drug that is absorbed into DNA and leads to the activation of cancer suppressor genes, which are genes that help control cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Gilteritinib is in a class of medications called kinase inhibitors. It works by blocking the action of a certain naturally occurring substance that may be needed to help cancer cells multiply. This study may help doctors find out if these different approaches are better than the usual approaches. To decide if they are better, the study doctors are looking to see if the study drugs lead to a higher percentage of patients achieving a deeper remission compared to the usual approach.

In this clinical trial, symptom monitoring (interactive voice response \[IVR\] is compared to automated telephone symptom management \[ATSM\] and telephone interpersonal counseling \[TIPC\]) for reducing symptom burden and psychological distress (depressive and anxiety symptoms) among people receiving oral anti-cancer treatment. Symptoms are the number one driver of treatment interruptions and unscheduled health services use. To reduce the risk of these events, symptom monitoring and management are necessary. However, these services are not implemented routinely, especially in the community oncology settings. Further, depressive and anxiety symptoms are a key barrier to enacting symptom self-management strategies. IVR is a form of symptom monitoring where patients, when called, enter their symptom ratings over the phone. Their symptom summary is sent to their provider, and patients may be advised to reach out to their oncology provider, based on their symptoms. The ATSM intervention combines IVR assessments with a Symptom Management and Survivorship educational handbook with self-management strategies. Patients receiving ATSM enter their symptom ratings over the phone and have their symptoms reported to their provider, but patients are also directed to the handbook for strategies to manage elevated symptoms. Patients receiving ATSM who report being anxious, discouraged, or sad will also receive TIPC, which targets psychological distress and its connection to social support and interpersonal communication. Information gathered from this study may help researchers learn more about the best ways to manage patient symptoms and improve patient outcomes.

This phase III trial compares the addition of an immunotherapy drug (durvalumab) to usual chemotherapy versus usual chemotherapy alone in treating patients with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as paclitaxel, doxorubicin, and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. There is some evidence from previous clinical trials that people who have a MammaPrint High 2 Risk result may be more likely to respond to chemotherapy and immunotherapy. Adding durvalumab to usual chemotherapy may be able to prevent the cancer from returning for patients with MP2 stage II-III hormone receptor positive, HER2 negative breast cancer.