Clinical Research Directory

Liquid Biomarker Study in Melanoma and Non-Melanoma Skin Cancers

The goal of this observational study is to study blood samples and compare them to other biospecimens and clinical outcomes in participants who have melanoma or non-melanoma skin cancers. The main question it aims to answer is: * Are blood based signatures able to predict progression-free survival (PFS)? Participants undergoing regular treatment for their skin cancer will provide blood samples.

Exploratory Study With Parallel Controls on the Safety and Efficacy of Neoadjuvant Low Branched-Chain Amino Acid Diet in Combination With Anti-PD-1 Monoclonal Antibody for Stage III Melanoma

1. Primary Objective: To evaluate the safety of a low branched-chain amino acid diet (60% of the normal dietary BCAA content) combined with anti-PD-1 monoclonal antibody as neoadjuvant therapy in patients with stage III melanoma, by documenting the incidence of all adverse events (AEs) and serious adverse events (SAEs), and analyzing changes from baseline in physical examinations, vital signs, and laboratory test results. 2. Secondary Objectives: To assess the pathological response rates (including pCR, near-pCR, pPR, and pNR) of the combination therapy in stage III melanoma; to evaluate the objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) and the immune-related RECIST (irRECIST) criteria; and to estimate event-free survival (EFS) and overall survival (OS) through long-term follow-up. 3. Exploratory Objectives: To investigate the quality of life (QoL) in patients receiving the low BCAA diet combined with anti-PD-1 therapy; and to identify predictive biomarkers for treatment outcome differences, such as immune-related gene signatures (e.g., PD-L1 expression) and driver gene mutations in somatic variants.

Liquid Biopsy Multi-Omics and Biomarker Development in Melanoma

This prospective, observational cohort study aims to explore the multi-omics profiles of liquid biopsies and develop clinical biomarkers in melanoma. Two hundred participants with pathologically confirmed acral or cutaneous melanoma who are scheduled to receive standard first-line immunotherapy will be enrolled. Blood samples will be collected at baseline and every 3 weeks during treatment, along with radiological assessments every 12 weeks. Tumor tissue will be obtained at surgery after approximately 3 months of therapy. Using microfluidic-based circulating tumor cell isolation, exosome enrichment, ctDNA analysis, and integrative multi-omics approaches, the study will compare molecular features across primary tumors, metastases, and liquid biopsy components. The primary outcomes are progression-free survival and overall survival, assessed up to 36 months. Secondary outcomes include changes in circulating tumor cell counts, ctDNA concentrations, exosomal biomarker levels, pathological response rate at surgery, and the predictive accuracy of a multi-omics model for treatment response. The findings are expected to provide a basis for personalized monitoring and treatment strategies in melanoma.

Study of AMXT 1501 and DFMO in Combination With Standard Therapies in Advanced Solid Tumors

This study will evaluate the safety, tolerability, and preliminary effectiveness of AMXT 1501 and DFMO when combined with standard treatments for advanced solid tumors. The trial includes two groups: * Cohort 1: Patients with ER+ / HER2- breast cancer receiving fulvestrant and capivasertib * Cohort 2: Patients with unresectable or metastatic cutaneous melanoma receiving pembrolizumab The Phase 1b portion will find the recommended Phase 2 dose (RP2D). The Phase 2 portion will further evaluate clinical activity at the RP2D using response criteria for solid tumors (RECIST 1.1). The study will also evaluate pharmacokinetics, pharmacodynamics, disease control, and overall safety.

Investigating Real-Time Immunotherapy Symptoms Study

The goal of this study is to evaluate the feasibility of using information from wearable devices and self-reported symptoms to remotely monitor patients during immunotherapy. The main questions it aims to answer are: * Is the digital remote patient monitoring tool feasible and acceptable to patients? * Do the alerts and guidance improve symptom management, quality of life, and engagement with the care team during treatment? Participants will: * Complete a demographic questionnaire at the beginning of the study and quality-of-life and health questionnaires at the beginning, midpoint, and end of study. * As feasible: At the beginning and end of the study, complete an in-person physical function assessment measuring balance (Short Physical Performance Battery). If participant is randomly assigned to the intervention group, they will also: * Complete weekly symptom ratings via digital remote patient monitoring tool * Wear a Fitbit activity tracker for 90 days. * At the end of the study, complete a semi-structured interview to provide feedback on the study.

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

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.

Sun Exposure and Activities After Skin Cancer: Optimization of mHealth Interventions

The purpose of this study is to evaluate 5 different smartphone administered sun protection interventions that aim to reduce unprotected sun exposure in melanoma survivors. Participants are asked to wear an ultraviolet (UV) device and an activity monitor (Actigraph) to measure their daily UV exposure and track their physical activity for three separate assessment weeks and complete daily surveys. After the first assessment week, eligible participants are assigned up to 5 different sun protection interventions that are administered through a smartphone application for 8 weeks. Following 8-week use of the sun protection interventions, participants complete another assessment week. At the end of the assessment week, participants provide feedback on the design and usability of the UV device, smartphone application and each of the sun protection interventions that they experienced. One year later, participants are contacted again to complete a final assessment week.

Superparamagnetic Iron Oxide for Sentinel Lymph Node Localization in Patients With Cutaneous Melanoma, a Randomized Phase III Multi-center Non- Inferiority Trial: MagMen-II

A randomized, international, phase III, multi-center, non- inferiority trial assessing the safety and efficacy of Magtrace® (superparamagnetic iron oxide, SPIO) in identification of lymph nodes in patients with cutaneous melanoma undergoing a sentinel lymph node biopsy (SLNB). Participants will be injected with both tracer methods Technetium (Tc99) plus Blue Dye (BD) and Magtrace®). They will undergo both a lymphoscintigraphy and a Magnetic Resonance Imaging (MRI) of the SLN basins. Before surgery, the participants will be randomly assigned on a 1:1 basis to either start the SLNB procedure using Tc99/BD and gamma-probe followed by Magtrace® and magnetic probe, or SLNB using Magtrace® followed by Tc99/BD. Randomization will be stratified by study site using permuted variable block sizes.

A Trial of LNS8801 With or Without Pembrolizumab in Patients With Refractory Melanoma

The goal of this clinical trial is to understand if a new drug called LNS8801 can safely treat patients with melanoma. The primary question to be answered is what is the average length of time during which melanoma does not grow or spread after starting treatment with LNS8801? Researchers will compare LNS8801 taken alone or LNS8801 taken together with another drug called pembrolizumab to other therapies as decided by the treating doctor. 135 patients will be randomly (like flipping a coin) placed in 3 treatment groups. In the first group (LNS8801 only) - Patients will take 125mg tablet of LNS8801 by mouth once per day every day for up to 2 years. In the second group (LNS8801 + pembrolizumab) - Patients will take 125mg tablet of LNS8801 by mouth once per day plus 200 mg of pembrolizumab by IV infusion once every 3 weeks for up to 2 years. In the third group, called Physician's Choice (PC), patients will receive chemotherapy (dacarbazine or temozolomide) or immunotherapy (pembrolizumab, nivolumab/relatlimab or nivolumab/ipilimumab) as determined by their treating physician. How often the patient visits the clinic visits will depend on the treatment group. Besides returning to the clinic for treatment, the patient will undergo periodic safety assessments and other required study procedures such as imaging assessments.

A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Melanoma

This is a Phase 2, multicenter, open-label study of lifileucel (tumor-infiltrating lymphocytes \[TIL\]) in participants with previously treated advanced melanoma

Phase Ib Study of AlpeliSib With PEmbroLizumab in Patients With mEtastatic Breast caNcer or melanomA (SELENA)

To find a recommended dose of the combination of alpelisib and pembrolizumab that can be given to patients with metastatic breast cancer or melanoma.

ctDNA for Risk Stratification in Melanoma

This study examines circulating tumor DNA (ctDNA) as a biomarker in patients with primary melanoma, prior to surgical excision. The hypothesis is that ctDNA may be detectable in pre-operative blood samples from patients with high-risk primary melanoma, potentially providing a baseline measurement for future disease monitoring.

Neoadjuvant Pucotenlimab Combined With Lenvatinib and Temozolomide in Resectable Stage IIB/III Acral Melanoma

This is a single-arm, open-label, single-center, Phase II exploratory clinical study evaluating the efficacy, safety, and tolerability of neoadjuvant pucotenlimab combined with lenvatinib and temozolomide in patients with resectable Stage IIB/III acral melanoma. After providing written informed consent, eligible subjects will receive neoadjuvant combination therapy consisting of pucotenlimab, lenvatinib, and temozolomide, with each treatment cycle lasting 3 weeks. Surgical resection will be performed after 3 cycles of treatment. Postoperative adjuvant therapy will be determined based on the pathological results of the surgical specimens. Subjects who do not achieve a major pathological response (MPR) will receive pucotenlimab maintenance therapy for a total of 1 year, while subjects who achieve an MPR will be exempt from adjuvant therapy. Treatment will continue until the completion of adjuvant therapy, disease progression, unacceptable toxicity, initiation of a new anti-tumor therapy, withdrawal of informed consent, loss to follow-up, death, or discontinuation determined by the investigator, whichever occurs first.

A Study of Biological, Genetic, and Constitutional Factors and Non-invasive Monitoring to Assess Personal Cancer Risks

The PRO-ACTIVE study aims to develop a clinical-translational program in the field of cancer prevention in all its phases (primary, secondary, and tertiary) to intervene before the clinical and radiological manifestation of the disease. It starts with risk prediction and leads to early diagnosis of the disease or recurrence in the subclinical phase. The PRO-ACTIVE study includes the following activities: * WP1: Integrated DNA-RNA approach for the identification of hereditary markers of predisposition to tumors * WP2: Global biological and molecular analysis of the host and tumor for the prevention and monitoring of recurrences * WP3: Analysis of the immunological status for the diagnosis of primary prevention and relapses in correlation to genetic and environmental factors * WP4: Study of the tumor microenvironment for recurrence prediction

A Phase II Clinical Trial on Neo-adjuvant Pembrolizumab in Patients With pT3b-T4a/b cN0M0 Melanoma.

This study, called NeoSenti, is exploring whether giving one dose of the immunotherapy drug pembrolizumab before surgery can help the immune system fight melanoma more effectively. The study includes adults with high-risk melanoma who do not show any signs of the cancer having spread on scans. Participants receive a single infusion of pembrolizumab six weeks before their scheduled sentinel lymph node biopsy. The goal is to see if this early treatment can reduce or eliminate tiny cancer cells that might already be in the lymph nodes but are too small to detect. After surgery, patients whose melanoma stage normally requires further treatment will continue with standard immunotherapy for one year. Others will move directly into follow-up care. All participants are monitored closely for five years with regular scans, blood tests, and check-ups to watch for any signs of recurrence and to ensure their safety.

PD-L1 Targeting Peptide Probe for PET Imaging of Solid Tumor

The objective of this study is to construct a noninvasive approach using radiolabbled peptide 68Ga-cPP-BCH PET/CT to detect the PD-L1 expression of tumor lesion in patients with lung cancer, melanoma and other solid tumor to identify patients benefiting from anti-PD-(L)1 treatment.

Navigation Intervention for Adolescent and Young Adult Cancer Survivors

The investigators propose to: 1) Adapt an evidence-based cancer-focused patient navigation (PN) program for the Adolescent and Young Adult (AYA) cancer survivor population; and 2) Plan and conduct an effectiveness-implementation trial of this program within Kaiser Permanente Southern California (KPSC). PLEASE NOTE: This study is awarded in two phases. The UG3 phase has been awarded for the first two years; upon successful completion of this phase by meeting pre-defined milestones, the National Cancer Institute (NCI) will provide funding for the second phase of the study (Years 3-6), which will allow our team to conduct a trial to determine the effectiveness of the implementation of the adapted PN program for the AYA cancer survivor population. This application is focused on the initial UG3 phase and will update the protocol for the UH3 trial upon successful completion of the UG3 milestones and receipt of the UH3 award. The primary objectives in the UG3 phase of the study are to adapt and tailor an existing PN program to meet the needs of AYA cancer survivors and the local clinical context via (a) interviews with key stakeholders (patients, clinicians, administrators) and (b) guidance from our AYA Primary Care Survivorship Council. The investigators will conduct a pilot study of the adapted PN program and refine the program to enhance acceptability to patients and clinicians, enhance feasibility and effectiveness, and develop and pilot evaluation tools and methods prior to the start of the UH3 phase of the trial, which will be a larger trial. Objectives will be updated for the UH3 phase once awarded.

EBNK-001 Allogeneic NK Cells With Low-Dose IL-15 ± Pembrolizumab in Advanced Solid Tumors

This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of EBNK-001 (allogeneic NK cells) given after lymphodepleting cyclophosphamide/fludarabine (CY/FLU) and supported with low-dose IL-15, administered either alone or in combination with pembrolizumab in adults with advanced/metastatic solid tumors. The study will determine a recommended Phase 2 dose (RP2D) and explore signals of clinical activity using RECIST-based response criteria.

Biomarker-Guided Allogeneic Single-Target or Dual-Target CAR-NK Cell Therapy for Advanced Solid Tumors

This Phase 1/2 study evaluates the safety, feasibility, and preliminary anti-tumor activity of allogeneic donor-derived CAR-NK cells in participants with advanced solid tumors. The CAR target antigen is selected for each participant after tumor profiling using a tissue biopsy and/or liquid biopsy. Participants will receive either a single-target or dual-target CAR-NK product based on the antigen profile.

A Phase 1 Study of TGI-5 as Monotherapy and in Combination With Nivolumab in Subjects With Locally Advanced/Metastatic Solid Tumors

This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary antitumor activity of TGI-5 as monotherapy and in combination with Nivolumab in subjects with unresectable locally advanced/metastatic solid tumors. The study consists of two parts: TGI-5 monotherapy (Phase 1a: including a dose escalation part and a dose expansion part), TGI-5 in combination with a fixed dose of Nivolumab (Phase 1b: including a dose escalation part and a dose expansion part).

Predicting Response to Anti-PD-1/PD-L1 Immunotherapy by Plasma Extracellular Vesicle Analysis

The objective of this prospective multicenter study is to evaluate whether the analysis of immunological biomarkers present in circulating extracellular vesicles is associated with the response to anti-PD-1/PD-L1 treatments in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) or unresectable melanoma. Patients will receive standard-of-care treatment and will be followed according to routine clinical practice. The study involves the collection of four study-specific blood samples at different time points during follow-up, as well as the collection of standard immunohistochemistry results, thoraco-abdomino-pelvic CT scans, and tumor DNA genotyping analyses performed as part of routine care. The study aims to determine: * whether baseline biomarkers in extracellular vesicles are associated with response to anti-PD-1/PD-L1 treatment, * how these biomarkers change over the course of treatment, and * to provide exploratory data for the development of predictive immunological response signatures.

IMmune checkPoint Inhibitor Related gonAdal toxiCiTy in Premenopausal Women and Men With Melanoma

This study aims to capture information regarding the effect of immune checkpoint inhibitor (ICI) treatment for melanoma on reproductive organ function and sex hormone levels. You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with melanoma (Stage II, III or IV) and you are planning to receive ICI treatment. Additional criteria will apply dependent upon your biological sex characteristics. All participants who choose to enroll in this study will be asked to complete a series of questionnaires and provide blood at 4 of their scheduled treatment visits. These visits are anticipated to add 30 minutes to the scheduled visit time. Male participants will also be asked to provide semen samples at 2 of their scheduled treatment visits. These visits are anticipated to add an additional 30 minutes to the scheduled visit time. No additional or novel treatments will be offered to participants who choose to enroll in this study, this is an observational study only. It is hoped this research will contribute important information regarding the potential toxic effects of ICI treatment on sexual and reproductive function in patients with melanoma who are receiving ICI treatment.

Neoadjuvant Pembrolizumab in Patients With Stage IIb/c Melanoma

A phase II double-blind placebo-controlled randomized trial. Patients with a clinical suspicion of a thick primary melanoma without clinical suspicion or evidence of lymph-node engagement will undergo a 3 mm punch biopsy to verify the diagnosis and ascertain eligibility. Patients will receive 1 cycle of pembrolizumab 400 mg or placebo and 4 weeks later undergo a wide local excision and sentinel lymph node biopsy according to the national guideline recommendations . The primary objective is to evaluate the pathological response of one cycle of neoadjuvant pembrolizumab in patients with biopsy-proven stage IIb/c melanoma. Secondary objectives include efficacy and safety analysis, as well as biomarker discovery.

SL-28 for Advanced Solid Tumours

Second Life Therapeutics is developing SL-28, an allogeneic, non-genetically modified cell-based therapy for the treatment of advanced solid tumours. The company has recently demonstrated a novel, non-genetic approach to modulate immune cell activity through targeted manipulation of the Universal Receptive System. The purpose of this open label, multi-center clinical trial is to evaluate the anti-tumor activity, safety, and pharmacokinetics, single-agent SL-28 in patients with a diverse array of solid tumors. The study includes an initial Phase 1 dose escalation to determine recommended dose(s) for expansion of SL-28 as a monotherapy and Phase 2 expansion cohorts. The study will enroll patients with advanced solid tumours, including those who failed previous lines of chemo- and immunotherapies.