This protocol describes prospective, open-label, blinded, randomized controlled, multicenter
pivotal studies to evaluate ALM-488.

This is a Phase 1, Open-Label, Dose Escalation and Expansion, Multicenter Study of Claudin
18.2-Targeted Chimeric Antigen Receptor T-cells in Subjects with Unresectable, Locally
Advanced, or Metastatic Gastric, Gastroesophageal Junction (GEJ), Esophageal, or Pancreatic
Adenocarcinoma

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 open-label research study is studying (Z)-endoxifen as a possible treatment for
pre-menopausal (still having periods) women with ER+/HER2- breast cancer. (Z)-endoxifen is a
selective estrogen receptor modulator or "SERM." SERMs work to treat cancer by blocking the
body's natural estrogen from binding to cancer cells. This study includes a pharmacokinetic
part (PK, how the drug works in your body) and a treatment part. The primary purpose of the
study is to see how (Z)-endoxifen works on tumor cell growth by monitoring a cancer marker
called Ki-67. Ki-67 will be measured by biopsy of the breast after about 4 weeks of
treatment. If your cancer is responding to treatment based on the Ki-67 results, you may
continue treatment up to 24 weeks or until surgery.

The PK part of the study will be enrolled first, enrolling about 18 study participants who
will all receive oral once daily (Z)-endoxifen treatment. 12 of these participants will be
randomly assigned to treatment with an equal (50/50) chance to be assigned to (Z)-endoxifen
or (Z)-endoxifen + goserelin (a medication given to block the ovaries from making estrogen
and is also called ovarian suppression). This part of the study will help select the dose of
(Z)-endoxifen to use in the treatment part by measuring the levels of (Z)-endoxifen in the
blood stream and determine how long it takes for the body to remove it.

About 160 study participants will be enrolled in the treatment part. The treatment part will
help to determine how oral once daily (Z)-endoxifen, when taken by itself, compares to oral
once daily exemestane (a medication that decreases the amount of estrogen in the body, also
known as an aromatase inhibitor) and monthly injections of goserelin. Exemestane and
goserelin taken together is a standard treatment regimen for premenopausal patients with
ER+/HER2- breast cancer. Study participants are randomly assigned to treatment with an equal
(50/50) chance to be assigned to (Z)-endoxifen or standard treatment.

Study participation is up to 24 weeks of treatment followed by surgery.

This phase II trial studies the effect of hypofractionated radiotherapy followed by surgery in treating patients with soft tissue sarcoma. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving hypofractionated radiotherapy followed by surgery may allow patients with sarcomas to be treated in a much more rapid and convenient fashion.

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.