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Study of FIH of STX-241 in Locally Advanced or Metastatic NSCLC Resistant to EGFR TKIs

Non-small Cell Lung Cancer (NSCLC)

The goal of this First-In-Human (FIH) Phase I/II trial is to establish the safety profile, determine the Recommended Phase II Dose (RP2D), explore the pharmacokinetic (PK) exposure and pharmacodynamic (PD) properties as well as assess the efficacy of STX-241/PFL-241, a mutant selective Central Nervous System (CNS)-penetrant fourth generation EGFR TKI, in participants with locally advanced or metastatic NSCLC that progressed during or following third generation EGFR TKI such as osimertinib due to C797X double acquired (secondary) mutations.

Nashville, TN18+ yrsAll genders
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A Study to Investigate the Safety and Efficacy of NST-628 Oral Tablets in Subjects With Solid Tumors

Oncology Β· MEK Mutation Β· RAF Gene Mutation

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.

Nashville, TN18+ yrsAll genders
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A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors

Cancer Β· Melanoma Stage III Β· Melanoma Stage IV

KB707-01 is a Phase 1/2, open-label, multicenter, dose escalation and expansion study. The study will evaluate the safety and tolerability of KB707 in adults with locally advanced or metastatic solid tumors who have progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or for whom there is no standard of care therapy as well as the safety, tolerability, preliminary efficacy, and immunologic effect of KB707 administered in combination with Opdualag to subjects with unresectable or metastatic melanoma. Subjects in dose escalation (Cohorts 1 through 3) and dose expansion (Cohort 4) will receive intratumoral injections of KB707 approximately every three weeks. Cohorts 1 through 4 are closed to new enrollment. Dose expansion Cohort 5 and Cohort 6 will evaluate subjects with advanced melanoma. Subjects in Cohort 5 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Opdualag (dosed every q4w per prescribing information). Subjects in Cohort 6 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Keytruda (dosed every q6w per prescribing information). All subjects will be treated until disease progression, death, unacceptable toxicity, symptomatic deterioration, achievement of maximal response, subject choice, Investigator decision to discontinue treatment, or the Sponsor determines to terminate the study.

Nashville, TN18+ yrsAll genders
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A Study to Assess Change in Disease Activity and Adverse Events in Adult Participants With Gynecologic Cancers Receiving Intravenous Infusion of IMGN151 as Monotherapy or in Combination With Other Therapies

Gynecologic Cancers Β· Platinum-Sensitive Ovarian Cancer Β· Fallopian Tube Cancer

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety and tolerability of IMGN151 when given as monotherapy and in combination with other anti-cancer therapies in adult participants with gynecologic cancers. IMGN151 is an investigational drug being developed for the treatment of gynecologic cancers. Participants are placed in 1 of 4 groups, called treatment arms. Each group receives a different treatment. Around 377 participants with gynecologic cancers will be enrolled in the study at approximately 50 sites worldwide. Participants will receive intravenous infusions of IMGN151 as monotherapy or in combination with anti-cancer therapies according to their assigned study arm. In Arm A, participants will receive IMGN151 in combination with carboplatin on Day 1 of each cycle. In Arm B, participants will receive IMGN151 in combination with olaparib, twice a day (BID) on Day 1 of each cycle. In Arm C, participants will receive IMGN151 in combination with bevacizumab on Day 1 of each cycle. In Arm D, participants will receive IMGN151 as monotherapy on Day 1 of each cycle. In Arm E, participants will receive IMGN151 as monotherapy on Day 1 of each cycle. In Arm F, participants will receive IMGN151 as monotherapy on Day 1 of each cycle. The total study duration will be approximately 3 years. 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 a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

Nashville, TN18+ yrsWomen
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A Study of Treatment for Medulloblastoma Using Sodium Thiosulfate to Reduce Hearing Loss

Childhood Medulloblastoma

This phase III trial tests two hypotheses in patients with low-risk and average-risk medulloblastoma. Medulloblastoma is a type of cancer that occurs in the back of the brain. The term, risk, refers to the chance of the cancer coming back after treatment. Subjects with low-risk medulloblastoma typically have a lower chance of the cancer coming back than subjects with average-risk medulloblastoma. Although treatment for newly diagnosed average-risk and low-risk medulloblastoma is generally effective at treating the cancer, there are still concerns about the side effects of such treatment. Side effects or unintended health conditions that arise due to treatment include learning difficulties, hearing loss or other issues in performing daily activities. Standard therapy for newly diagnosed average-risk or low-risk medulloblastoma includes surgery, radiation therapy, and chemotherapy (including cisplatin). Cisplatin may cause hearing loss as a side effect. In the average-risk medulloblastoma patients, this trial tests whether the addition of sodium thiosulfate (STS) to standard of care chemotherapy and radiation therapy reduces hearing loss. Previous studies with STS have shown that it may help reduce or prevent hearing loss caused by cisplatin. In the low-risk medulloblastoma patients, the study tests whether a less intense therapy (reduced radiation) can provide the same benefits as the more intense therapy. The less intense therapy may cause fewer side effects. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The overall goals of this study are to see if giving STS along with standard treatment (radiation therapy and chemotherapy) will reduce hearing loss in medulloblastoma patients and to compare the overall outcome of patients with medulloblastoma treated with STS to patients treated without STS on a previous study in order to make sure that survival and recurrence of tumor is not worsened.

Knoxville, Nashville, TN4–21 yrsAll genders
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Tebentafusp Regimen Versus Investigator's Choice in Previously Treated Advanced Melanoma (TEBE-AM)

Advanced Melanoma

The purpose of this study is to evaluate the efficacy and safety of tebentafusp-based regimens, including tebentafusp monotherapy and in combination with anti-PD1 vs investigator choice (including clinical trials of investigational agents, salvage therapy per local standard of care \[SoC\], best supportive care \[BSC\] on protocol survivor follow up) in patients with advanced non-ocular melanoma.

Knoxville, TN18+ yrsAll genders
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Clinical Trial of an Anti-cancer Drug, CA-4948 (Emavusertib), in Combination With Chemotherapy Treatment (FOLFOX Plus Bevacizumab) in Metastatic Colorectal Cancer

Metastatic Colorectal Adenocarcinoma Β· Stage III Colorectal Cancer AJCC v8 Β· Stage IV Colorectal Cancer AJCC v8

This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLFOX, fluorouracil and oxaliplatin, 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. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.

Nashville, TN18+ yrsAll genders
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Study of CD19 Allogeneic Memory T-cell Therapy for Relapsed/Refractory CD19+ Leukemia

Acute Lymphoblastic Leukemia, in Relapse Β· Acute Lymphoblastic Leukemia, Refractory Β· Pediatric ALL

This is a Phase I clinical study evaluating the safety and maximum tolerated dose of a novel CAR T-cell product: allogeneic memory (CD45RA- negative) T-cells expressing a CD19-specific CAR 41BBz (CD19-CAR.CD45RA- negative T-cells) for the treatment of patients ≀ 21 years old with relapsed and/ or refractory CD19-positive leukemia. Primary Objective To determine the maximum tolerated dose (MTD) and characterize the safety profile and dose-limiting toxicities (DLTs) of treatment with allogeneic CD19-CAR.CD45RA-negative T-cells in pediatric, adolescent and young adult patients ≀ 21 years of age, with relapsed and/or refractory CD19-positive leukemia. Secondary Objectives * To evaluate the anti-leukemic activity of allogeneic CD19-CAR.CD45RA-negative T-cells. * To determine rates and severity of graft-versus-host-disease (GVHD) after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells. Exploratory Objectives * To study the expansion, persistence and phenotype of allogeneic CD19-CAR.CD45RA-negative T-cells. * To characterize the cytokine profile in the peripheral blood and CSF after treatment with allogeneic CD19-CAR.CD45RA-negative T-cells. * To assess whether allogeneic CD19-CAR.CD45RA-negative T-cells acquire functional versus exhaustion-associated epigenetic programs. * To determine immune reconstitution post treatment, and the clonal structure and endogenous repertoire of allogeneic CD19-CAR.CD45RA-negative T-cells and relate inferred specificity to CAR response profiles. * To characterize incidence and mechanisms of relapse post-therapy with allogeneic CD19-CAR.CD45RA-negative T-cells.

Memphis, TNUp to 21 yrsAll genders
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Trastuzumab Deruxtecan (DS-8201a) for the Treatment of Recurrent or Refractory Osteosarcoma, Wilms Tumor, and Desmoplastic Small Round Cell Tumor

Desmoplastic Small Round Cell Tumor Β· Osteosarcoma Β· Recurrent Desmoplastic Small Round Cell Tumor

This phase I/II trial studies the effects of trastuzumab deruxtecan (DS-8201a) in treating patients with osteosarcoma, Wilms tumor (WT) or desmoplastic small round cell tumor (DSRCT) that is newly diagnosed or has come back after a period of improvement (recurrent) or that has not responded to previous treatment (refractory). Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It 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.

Memphis, Nashville, TN12–39 yrsAll genders
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CAR T-cell Long-Term Follow-Up, Quality of Life and Adverse Reactions

B-Cell Acute Lymphoblastic Leukemia (B-ALL)

To learn more about the long-term health in patients treated for B-Cell Acute Lymphoblastic Leukemia (B-ALL) with Cluster of Differentiation antigen 19 (CD19) -redirected chimeric antigen receptor (CAR) T-cells. Primary Objective: To evaluate the feasibility of conducting standardized clinical assessments of pediatric, adolescent and young adult (AYA) B-ALL survivors post CD19-CAR T-cell therapy, treated at multiple institutions, leveraging the St Jude Lifetime Cohort (SJLIFE) clinical and research infrastructure. Exploratory Objectives: * To describe the prevalence of persistent and new/late-onset health conditions developing β‰₯2-years post CD19-CAR T-cell therapy in survivors of pediatric and AYA B-ALL. * To characterize neurocognitive and neurologic function in survivors β‰₯2-years post CD19- CAR T-cell therapy. * To characterize immune health in survivors β‰₯2-years post CD19-CAR T-cell therapy. * To characterize functional status in survivors β‰₯2-years post CD19-CAR T-cell therapy.

Memphis, TNAll agesAll genders
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A Trial to Learn How Safe AZD9750 is and How Well it Works in People With Metastatic Prostate Cancer When Given With or Without Other Anticancer Drugs

Prostate Cancer

ANDROMEDA is a first-in-human, Phase I/II, open-label, multicenter study of AZD9750 in participants with metastatic prostate cancer. The trial evaluates safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy of AZD9750 as monotherapy and in combination with saruparib.

Nashville, TN18+ yrsMen
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Collection and Storage of Tissue and Blood Samples From Patients With Cancer

Hematopoietic and Lymphatic System Neoplasm Β· Malignant Solid Neoplasm Β· Metastatic Malignant Solid Neoplasm

This study collects and stores tissue and blood samples from patients with cancer. Collecting and storing samples of tissue and blood from patients with cancer to study in the laboratory may help scientists create new and better models to learn about cancer and to test new cancer drugs.

Memphis, TN0.2+ yrsAll genders
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FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3

Urinary Bladder Neoplasms Β· Neoplasm Metastasis Β· Ureteral Neoplasms

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of Vepugratinib by itself or when it is combined with other medicines that treat cancer. Vepugratinib 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). Study participation could last up to approximately 6 years, depending on which part of the study you join.

Nashville +more, TN18+ yrsAll genders
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