Clinical Research Directory

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

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.

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.

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.

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.

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.

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.

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.

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).

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.

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

Predicting Response to Immunotherapy From Analysis of Live Tumor Biopsies

This study will collect tumor specimens with correlated clinical and demographic data from patients who are undergoing a biopsy or similar procedure to obtain tumor tissue as a normal course of their medical management or diagnostic work-up for suspected or confirmed cancer.

CARE-Melanoma Trial

Melanoma, a serious skin cancer, is increasingly prevalent in Canada. Surgical intervention is essential but poses significant physical and emotional challenges. Rehabilitation is crucial for recovery, helping patients regain strength and confidence while addressing psychological needs. In Ontario, new neoadjuvant chemotherapy regimens are being introduced to improve outcomes by shrinking tumors before surgery. Despite advancements, pre-habilitation and early post-operative rehabilitation services for melanoma patients are currently lacking. This pilot trial aims to evaluate the feasibility and effectiveness of pre- and post-surgery rehabilitation strategies for melanoma patients. The purpose of this pilot trial is to determine the feasibility and preliminary effectiveness of a rehabilitation strategy for individuals with melanoma pre- and post-surgery.

Investigation of the ROle of faT and inflAmmaTory Cells in mElanoma

This study is a retrospective, proof-of-concept sample study to investigate a novel histological finding within the primary melanoma tumour in a large population of melanoma patients to assess its prognostic significance. This is a aims to validate the striking observation that a cross-talk between fat cells and leukocytes at the primary melanoma site promotes metastasis. In our unpublished pilot study, we have discovered an interesting finding whereby inflammatory cells extend from the tumour to and invading fat in the subcutaneous tissue and/or around the appendageal structures in the dermal skin in metastatic melanomas with distinct architectural changes within the fat. This finding was consistently present in metastatic and absent in non-metastatic melanomas. This new finding has both clinical and pathophysiological credence. Archival tissue blocks or human cell lines will be used in the first instance. As mitigation, experiments will be repeated with conditioned media obtained from co-culture of mixed primary immune cells obtained from peripheral blood mononuclear cell (PBMCs) and adipocytes induced from stem cells. This study aims to: * Investigate if the crosstalk between fat cells and tumour-infiltrating inflammatory cells defines the aggressiveness of primary cutaneous melanomas. * Identify and perform biological spatial analysis of the inflammatory cells between the tumour and fat in the primary tumours. * Investigate the interactions of fat cells and/or inflammatory cells in mediating melanoma cellular plasticity. The patients have not provided consent and will be justified in this application

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.

Reflectance Confocal Microscopy and Molecular Correlation in Atypical Melanocytic Lesions

This observational, prospective cohort study aims to evaluate the diagnostic relevance of Reflectance Confocal Microscopy (RCM) features in atypical melanocytic lesions scheduled for surgical excision, and to correlate these imaging features with molecular profiles obtained through Next-Generation Sequencing (NGS). Approximately 200 consecutive lesions, including atypical nevi and early-stage melanomas, will be analyzed from patients attending the Videomicroscopy and Confocal Clinic at the Dermatology Department of the University Hospital of Modena. The primary objective is to assess the diagnostic significance of RCM features-specifically atypical cells and disarrangement of the dermoepidermal junction (DEJ)-for early detection of melanoma. Secondary objectives include correlating RCM morphological patterns with NGS-derived genetic alterations and identifying molecular signatures that differentiate early-stage melanomas from benign nevi. All procedures are performed as part of routine clinical care, including dermoscopic and confocal evaluation, surgical excision, histopathology, and molecular analysis on formalin-fixed, paraffin-embedded blocks. Data will be anonymized, securely stored, and analyzed to determine associations between imaging and genetic variables. This study integrates morphological and molecular data to refine diagnostic workflows and improve early melanoma detection.

Neutrophil Biomarker Test for Predicting Clinical Benefit From Immunotherapy Based on Flow Cytometry Analysis

The NeutroFlow study is a multi-center clinical trial designed to develop a computational model that converts flow cytometry results into a prediction of clinical benefit. The study analyzes Ly6Ehi neutrophils in biological samples from patients treated with immune checkpoint inhibitors to evaluate their likelihood of benefiting from treatment. Blood samples are collected prior to treatment and used to support the ongoing development of the algorithm.

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.

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.

Pan-tumor MRD Study

The purpose of this observational study is to collect clinical information, blood, and tumor tissue samples from participants diagnosed with stage I, stage II, or operable stage III cancer in select solid tumors. The information collected will be used to develop tests to better understand cancer, for example, to improve cancer detection and to assess the risk of cancer coming back. Participants will receive routine standard of care from their doctor and their involvement is expected to last for approximately five and a half (5.5) years.