This phase II trial studies the effect of hormonal therapy given after (adjuvant) combination pertuzumab/trastuzumab in treating patients with hormone receptor positive, HER2 positive breast cancer. The drugs trastuzumab and pertuzumab are both monoclonal antibodies, which are disease-fighting proteins made by cloned immune cells. Estrogen can cause the growth of breast cancer cells. Hormonal therapy, such as letrozole, anastrozole, exemestane, and tamoxifen, block the use of estrogen by the tumor cells. Giving hormonal therapy after pertuzumab and trastuzumab may kill any remaining tumor cells in patients with breast cancer.

A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone
(fludarabine/cytarabine/gemtuzumab ozogamicin [GO]) improves survival of
children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are
unable to receive additional anthracyclines, or in 2nd relapse.

The goal of this clinical trial is to evaluate the safety of TOS-358 in adults with select
solid tumors who meet study enrollment criteria. The main questions it aims to answer are:

1. what is the maximum tolerated dose and recommended dose for phase 2?

2. how safe and tolerable is TOS-358 at different dose levels when taken orally once or
twice per day?

This is a Phase 1b open-label, 2-part study in 2 treatment groups. The 2 treatment groups are
as follows:

Treatment Group 1: OP-1250 in combination with ribociclib (KISQALI, Novartis Pharmaceuticals
Corporation).

Treatment Group 2: OP-1250 in combination with alpelisib (PIQRAY, Novartis Pharmaceuticals
Corporation).

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 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.

Genes contain genetic code which tell the body which proteins to make. Many types of cancer
are caused by changes, or mutations, in a gene called KRAS. Researchers are looking for ways
to stop the actions of abnormal proteins made from the mutated KRAS gene. The so-called G12D
mutation in the KRAS gene is common in people with some solid tumors.

ASP3082 is a potential new treatment for certain solid tumors in people who have the G12D
mutation in their KRAS gene. Before ASP3082 is available as a treatment, the researchers need
to understand how it is processed by and acts upon the body. This information will help find
a suitable dose and to check for potential medical problems from the treatment.

People in this study will be adults with locally advanced, unresectable or metastatic solid
tumors with the G12D mutation in their KRAS gene (G12D mutation). 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. They will have
been previously treated with standard therapies or refused to receive those treatments. In
the European Union (EU) and South Korea, people who have refused to receive treatment with
standard therapies cannot take part.

The main aims of the study are: to check the safety of ASP3082 by itself and together with
cetuximab (a common cancer medicine), how well it is tolerated, and to find a suitable dose
of ASP3082 by itself and together with cetuximab.

This is an open-label study. This means that people in this study and clinic staff will know
that they will receive ASP3082.

This study will be in 2 parts. In Part 1, different small groups of people will receive lower
to higher doses of ASP3082, by itself, or together with cetuximab. Only people with
colorectal cancer will receive ASP3082 together with cetuximab. Any medical problems will be
recorded at each dose. This is done to find suitable doses of ASP3082 by itself or together
with cetuximab to use in Part 2 of the study. The first group will receive the lowest dose of
ASP3082. A medical expert panel will check the results from this group and decide if the next
group can receive a higher dose of ASP3082. The panel will do this for each group until all
groups have received ASP3082 (by itself or together with cetuximab) or until suitable doses
have been selected for Part 2.

In Part 2, other different small groups of people will receive ASP3082 by itself or together
with cetuximab, with the most suitable doses worked out from Part 1. This will help find a
more accurate dose of ASP3082 to use in future studies.

ASP3082, and cetuximab (if used), will be given through a vein. This is called an infusion.
Each treatment cycle is 21 days long. They will continue treatment until: they have medical
problems from the treatment they can't tolerate; their cancer gets worse; they start other
cancer treatment; they ask to stop treatment; they do not come back for treatment.

People will visit the clinic on certain days during their treatment, with extra visits during
the first 2 cycles of treatment. During these visits, the study doctors will check for any
medical problems from ASP3082 by itself or together with cetuximab. At some visits, other
checks will include a medical examination, echocardiogram (ECHO) or multigated acquisition
(MUGA) scan, blood and urine tests and vital signs. Vital signs include temperature, pulse,
breathing rate, and blood pressure. (Blood oxygen levels will also be checked for people
treated with ASP3082 together with cetuximab.) Tumor samples will be taken during certain
visits during treatment and when treatment has finished.

People will visit the clinic within 7 days after stopping treatment. The study doctors will
check for any medical problems from ASP3082 by itself or together with cetuximab. Other
checks will include a medical examination, echocardiogram (ECHO) or multigated acquisition
(MUGA) scan, urine and blood tests and vital signs. After this, people will continue to visit
the clinic every 9 weeks. This is to check the condition of their cancer. They will do this
until 45 weeks after treatment stopped, or if their cancer is worse, they start other cancer
treatment, they ask to stop treatment, or they do not come back for treatment.

Also, people may visit the clinic at 30 days and 90 days after stopping treatment. At the
30-day visit, the study doctors will check for any medical problems from ASP3082 by itself or
together with cetuximab. People will have their vital signs checked and have some bloo

This phase III trial studies how well lenalidomide and dexamethasone works with or without daratumumab-hyaluronidase in treating patients with high-risk smoldering myeloma. Drugs used in chemotherapy, such as lenalidomide, 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. Anti-inflammatory drugs, such as dexamethasone lower the bodys immune response and are used with other drugs in the treatment of some types of cancer. Daratumumab-hyaluronidase is a monoclonal antibody, daratumumab, that may interfere with the ability of cancer cells to grow and spread, and hyaluronidase, which may help daratumumab work better by making cancer cells more sensitive to the drug. Giving lenalidomide and dexamethasone with daratumumab-hyaluronidase may work better in treating patients with smoldering myeloma.

This phase III trial studies how well active surveillance help doctors to monitor subjects with low risk germ cell tumors for recurrence after their tumor is removed. When the germ cell tumors has spread outside of the organ in which it developed, it is considered metastatic. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, 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. The trial studies whether carboplatin or cisplatin is the preferred chemotherapy to use in treating metastatic standard risk germ cell tumors.

This phase III trial compares the effect of continuation of treatment with pembrolizumab (usual approach) to observation only at preventing cancer from coming back in patients with early-stage triple-negative breast cancer (TNBC) who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. The usual approach for patients with early-stage TNBC who receive preoperative chemotherapy plus pembrolizumab is to continue to receive pembrolizumab for up to 27 weeks after surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help researchers determine if observation is as good as receiving pembrolizumab for 27 weeks after surgery in triple-negative breast cancer patients who achieved a pathologic complete response after preoperative treatment with chemotherapy and pembrolizumab.

This phase III trial uses the Decipher risk score to guide therapy selection. Decipher score is based on the activity of 22 genes in prostate tumor and may predict how likely it is for recurrent prostate cancer to spread (metastasize) to other parts of the body. Decipher score in this study is used for patient selection and the two variations of treatment to be studied: intensification for higher Decipher score or de-intensification for low Decipher score. Patients with higher Decipher risk score will be assigned to the part of the study that compares the use of 6 months of the usual treatment (hormone therapy and radiation treatment) to the use of darolutamide plus the usual treatment (intensification). The purpose of this section of the study is to determine whether the additional drug can reduce the chance of cancer coming back and spreading in patients with higher Decipher score. The addition of darolutamide to the usual treatment may better control the cancer and prevent it from spreading. Alternatively, patients with low Decipher risk score will be assigned to the part of the study that compares the use of radiation treatment alone (de-intensification) to the usual approach (6 months of hormone therapy plus radiation). The purpose of this part of the study is to determine if radiation treatment alone is as effective compared to the usual treatment without affecting the chance of tumor coming back in patients with low Decipher score prostate cancer. Radiation therapy uses high energy to kill tumor cells and reduce the tumor size. Hormone therapy drugs such as darolutamide suppress or block the production or action of male hormones that play role in prostate cancer development. Effect of radiation treatment alone in patients with low Decipher score prostate cancer could be the same as the usual approach in stabilizing prostate cancer and preventing it from spreading, while avoiding the side effects associated with hormonal therapy.