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Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial)

Multiple Cancer Types

This phase II ADC MATCH screening and multi-sub-study treatment trial is evaluating whether biomarker-directed treatment with one of three antibody-drug conjugates (ADCs) (sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan) works in treating patients with solid tumor cancers that have high expression of the Trop-2, nectin-4, or HER2 proteins and that may have spread from where they first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or to other places in the body (metastatic). Precision medicine is a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, or treat disease in a way that is tailored to the patient. ADCs such as sacituzumab govitecan, enfortumab vedotin, and trastuzumab deruxtecan are monoclonal antibodies attached to biologically active drugs and are a form of targeted therapy. Sacituzumab govitecan is a monoclonal antibody, called sacituzumab, linked to a drug called govitecan. Sacituzumab attaches to a protein called Trop-2 on the surface of tumor cells and delivers govitecan to kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of tumor cells. Enfortumab attaches to a protein called nectin-4 on tumor cells in a targeted way and delivers vedotin to kill them. Trastuzumab deruxtecan is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Personalized treatment with sacituzumab govitecan, enfortumab vedotin, or trastuzumab deruxtecan may be an effective treatment option for patients with advanced or metastatic solid tumors that screen positive for high expression of Trop-2, nectin-4, or HER2, respectively.
Adrenocortical, Bladder, Breast, Cervical, Colon, Dermatologic, Esophageal, GIST, Gastric/Gastroesophageal, Gastrointestinal, Gynecologic, Head/Neck, Kidney (Renal Cell), Liver, Lung, Melanoma, Miscellaneous, Ovarian, Pancreatic, Prostate, Rectal, Sarcoma, Thyroid, Urologic, Uterine
II
Keedy, Vicki
NCT06311214
ETCMD10397

A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression

Miscellaneous

The goal of this study is to test A2B395, an allogeneic logic-gated Tmod CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and other solid tumors that express EGFR and have lost HLA-A\*02 expression.

The main questions this study aims to answer are:

* Phase 1: What is the recommended dose of A2B395 that is safe for patients
* Phase 2: Does the recommended dose of A2B395 kill the solid tumor cells and protect the patient's healthy cells

Participants will be required to perform study procedures and assessments, and will also receive the following study treatments:

* Enrollment in BASECAMP-1 (NCT04981119)
* Preconditioning lymphodepletion (PCLD) regimen
* A2B395 Tmod CAR T cells at the assigned dose
Miscellaneous
I/II
Ciombor, Kristen
NCT06682793
VICCPHI25031

FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3

Miscellaneous

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Miscellaneous
I
Rini, Brian
NCT05614739
VICCURO24518

A Study of CLSP-1025 in Adult Patients With Solid Tumors That Harbor the p53 R175H Mutation

Miscellaneous

Phase 1 dose escalation and expansion study of CLSP-1025, a first-in-class HLA-A\*02:01 specific T cell engager (TCE) targeting solid tumors that harbor the p53 R175H mutation.
Miscellaneous
I
Berlin, Jordan
NCT06778863
VICCPHI24572

Study of RYZ401 in Subjects With Solid Tumors Expressing SSTRs.

Miscellaneous

The primary objectives are to determine the recommended Phase 2 dose (RP2D) and optimal treatment regimen, characterize safety and tolerability, and evaluate preliminary efficacy of RYZ401 in subjects with NETs and other selected solid tumors expressing SSTRs.
Miscellaneous
I
Ramirez, Robert
NCT07165132
VICCPHI25050

A Phase 1b/2 Study of CAR T Cell Therapy Targeting CD19 and BCMA in Participants With Relapsed or Refractory AL Amyloidosis.

Miscellaneous

Open-label Phase 1b/2 study with primary objective of this study is to evaluate the safety, tolerability and efficacy of AZD0120 in participants with light chain (AL) amyloidosis.
Miscellaneous
I/II
Baljevic, Muhamed
NCT07081646
VICCCTTP25021

Pilot Study of Bone Mineral Density Changes During Anti-PD-1 Immunotherapy

Miscellaneous

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and work by blocking protein interactions that normally prevent the immune system from recognizing and destroying cancer cells. However, these agents, now approved for over 15 types of cancers and for both early-stage and metastatic disease, are capable of causing inflammation in any organ system of the body that can lead to organ damage, dysfunction, and even death in rare cases. Some patients may suffer acute and treatable complications like joint pain, but some may have irreversible complications like hypothyroidism that requires daily, life-long medication. It is therefore important to fully understand the different types of damage ICIs can cause to better monitor patients receiving ICI therapy.

A rising concern from recent reports in the literature is that ICIs may weaken bone and increase the risk of fractures. In this study, the investigators aim to characterize how ICIs impact the bone by examining several factors in patients undergoing curative-intent ICI treatment either alone or in combination with chemotherapy: bone mineral density, bone volume, and markers of bone turnover in the blood. The study will use two imaging techniques to assess bone mineral density and volume. DXA (dual X-ray absorptiometry) imaging uses low-dose X-rays to measure how dense (or strong) bones are and is often used to diagnose or assess the risk of osteoporosis. High-resolution peripheral quantitative computed tomography (HRpQCT) is a 3D imaging technology that can quantify bone structure and volume and offers high resolution that can be used to assess bone in smaller bones of the peripheral skeleton.

The investigators hypothesize that ICI treatment will weaken bones and increase the risk of fractures. As ICI therapy is relatively new, a rising number of patients may be at risk of fractures or have low bone density that is not being monitored because there are no guidelines in place notifying physicians of this potential risk to patients. This is study will provide important preliminary data that will be the basis for larger studies in the future aiming to better monitor and potentially treat bone weakening in patients treated with ICIs to reduce the pain, inconvenience, and complications from fragility fractures.
Miscellaneous
N/A
Sharpe, Jessica
NCT07555210
VICCMD25019

FOG-001 in Locally Advanced or Metastatic Solid Tumors

Miscellaneous

The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic solid tumors or in participants with familial adenomatous polyposis (FAP).
Miscellaneous
I/II
Ciombor, Kristen
NCT05919264
VICCPHI24562

A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors

Miscellaneous

This is a two-part Phase 1, open label, multi-center, single arm, non-randomized, multiple dose, safety, pharmacokinetic (PK) and preliminary efficacy study of single agent NST-628 in adult patients with MAPK pathway mutated/dependent advanced solid tumors who have exhausted standard treatment options.
Miscellaneous
I
Berlin, Jordan
NCT06326411
VICC-DTPHI23579

Zanzalintinib Versus Everolimus in Participants With Locally Advanced or Metastatic Neuroendocrine Tumors

Miscellaneous

The primary purpose of this study is to assess the effectiveness of zanzalintinib compared to everolimus in participants with previously treated, unresectable, locally advanced or metastatic neuroendocrine tumors.
Miscellaneous
II/III
Gibson, Mike
NCT06943755
VICCGI25020