This is a Phase III open-label study to assess if camizestrant improves outcomes compared to
standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with
intermediate-high or high risk for disease recurrence who completed definitive locoregional
therapy (with or without chemotherapy). The planned duration of treatment in either arm
within the study will be 7 years.

This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the
Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with
Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR
Inhibitor-Refractory/Relapsed Cholangiocarcinoma

This phase II trial tests how well evaluating circulating tumor deoxyribonucleic acid (ctDNA) works to guide therapy-change decisions in treating patients with triple-negative breast cancer (TNBC) that has spread from where it first started (primary site) to other places in the body (metastatic). This study wants to learn if small pieces of DNA associated with a tumor (called circulating tumor DNA, or ctDNA) can be detected in investigational blood tests during the course of standard chemotherapy treatment for breast cancer, and whether information from such investigational ctDNA blood testing could possibly be used as an early indication of chemotherapy treatment failure. It is hoped that additional information from investigational blood testing for ctDNA could help doctors to switch more quickly from a standard chemotherapy treatment that typically has significant side effects and which may not be working, to a different standard treatment regimen against TNBC, called sacituzumab govitecan. Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a chemotherapy drug, called irinotecan. hRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as TROP2 receptors, and delivers irinotecan to kill them. Studying ctDNA may assist doctors to change therapy earlier if needed, and may improve health outcomes in patients with metastatic TNBC.

This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).

This is a Phase 1/2, open-label, first-in-human, dose-escalation and expansion study of
SRF114, a monoclonal antibody that targets CCR8, as a monotherapy in patients with solid
tumors.

This phase I/II trial tests the safety and efficacy of split-course adaptive radiation therapy in combination with immunotherapy with or without chemotherapy for the treatment of patients with stage IV lung cancer or lung cancer that that has spread to nearby tissue or lymph nodes (locally advanced). Radiation therapy is a standard cancer treatment that uses high energy rays to kill cancer cells and shrink tumors. Split-course adaptive radiation therapy uses patient disease response to alter the intensity of the radiation therapy. Immunotherapy with monoclonal antibodies such as pembrolizumab, ipilimumab or 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 like carboplatin, pemetrexed, and paclitaxel 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. Giving split-course adaptive radiation therapy with standard treatments like immunotherapy and chemotherapy may be more effective at treating stage IV or locally advanced lung cancer than giving them alone.

This study will have two Phases: Phase 1a and Phase 1b. The goal of Phase 1a of this clinical
study is to learn more about the safety, tolerability and dosing of study drug KITE-197, in
participants with relapsed or refractory large B-cell lymphoma (r/rLBCL). The goal of Phase
1b of this clinical study is learn about the effectiveness of the recommended dose of
KITE-197 in participants with r/r LBCL.

The primary objectives of this study are:

Phase 1a: To evaluate the safety of KITE-197 in participants with r/r LBCL and determine the
target dose level for Phase 1b.

Phase 1b: To evaluate the efficacy of KITE-197 in participants with r/r LBCL as measured by
the complete remission (CR) rate.

This is an umbrella study evaluating the efficacy and safety of multiple treatment
combinations in participants with metastatic or inoperable locally advanced breast cancer.

The study will be performed in two stages. During Stage 1, four cohorts will be enrolled in
parallel in this study:

Cohort 1 will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have
received no prior systemic therapy for metastatic or inoperable locally advanced
triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort).

Cohort 2 will consist of participants who had disease progression during or following 1L
treatment with chemotherapy for metastatic or inoperable locally-advanced TNBC and have not
received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort).

Cohort 3 will consist of participants with locally-advanced or metastatic HR+, HER2-negative
disease with PIK3CA mutation who may or may not have had disease progression during or
following previous lines of treatment for metastatic disease (HR+cohort).

Cohort 4 will consist of participants with locally-advanced or metastatic HER2+ /HER2-low
disease with PIK3CA mutation who had disease progression on standard-of-care therapies (HER2+
/HER2-low cohort).

In each cohort, eligible participants will initially be assigned to one of several treatment
arms (Stage 1). In addition, participants in the 2L CIT-nave cohort who experience disease
progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be
eligible to continue treatment with a different treatment combination (Stage 2), provided
Stage 2 is open for enrollment.

Patients will be registered prior to, during or at the completion of neoadjuvant chemotherapy
(Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on Day 1 every 21 days for 3-4
cycles). Registered patients who progress during neoadjuvant chemotherapy will not be
eligible for iCRS and will be removed from the study.

Following completion of neoadjuvant chemotherapy, interval cytoreductive surgery (iCRS) will
be performed in the usual fashion in both arms. Patients will be randomized at the time of
iCRS (iCRS must achieve no gross residual disease or no disease >1.0 cm in largest diameter)
to receive HIPEC or no HIPEC. Patients randomized to HIPEC (Arm A) will receive a single dose
of cisplatin (100mg/m2 IP over 90 minutes at 42 C) as HIPEC. After postoperative recovery
patients will receive standard post-operative platinum-based combination chemotherapy.
Patients randomized to surgery only (Arm B) will receive postoperative standard chemotherapy
after recovery from surgery.

Both groups will receive an additional 2-3 cycles of platinum-based combination chemotherapy
per institutional standard (Paclitaxel 175 mg/m2 IV over 3 hours and Carboplatin AUC 6 IV on
Day 1 every 21 days for 2-3 cycles) for a maximum total of 6 cycles of chemotherapy
(neoadjuvant plus post-operative cycles) followed by niraparib individualized dosing until
progression or 36 months (if no evidence of disease).

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.