Clinical Research Directory

A Study to Learn About the Study Medicine Called PF-08046032 in People With Advanced Cancers

The purpose of this study is to learn about the effects of a new study medicine called PF-08046032, when taken alone and when taken with another medicine called sasanlimab, for the treatment of advanced cancers. The effects are studied in adult participants with certain types of lymphomas or solid tumors that are advanced or metastatic (spread to other parts of the body). The study has three parts: * Part A will test PF-08046032 alone at increasing dose levels in participants with certain lymphomas (cancer that begins in cells of the immune system) and in participants with certain solid tumors whose disease has worsened on or after standard treatments. * Part B will test PF-08046032 (at selected doses) and sasanlimab in participants with certain solid tumors, including those whose disease has worsened on or after standard treatments as well as participants before receiving standard treatments. * Part C will further test the combination of PF-08046032 and sasanlimab in participants with specific types of solid tumors based on the results from Part A and Part B of the study. All participants will receive the study drug PF-08046032. Only participants in Part B and Part C of the study will also receive sasanlimab. PF-08046032 will be given as an intravenous (IV) infusion, which means it will be injected directly into a vein. Sasanlimab will be given as a subcutaneous injection, which means it will be injected under the skin.

Brentuximab Vedotin for Newly Diagnosed cHL in Chinese CAYA Based on PET/CT Assessment

Generally, pediatric patients tolerate acute toxicities but are vulnerable to late effects. Thus, increasing chemotherapy intensity to achieve more rapid complete early response to limit radiation therapy is worth testing. In this CCCG-HL-2024 study, Brentuximab vedotin (Bv) was used to replace VCR and bleomycin in the ABVE-PC regimen in the previous CCCG-HD-2018 study, respectively, to form a Bv-AEPC regimen for the treatment of newly diagnosed classic Hodgkin lymphoma (cHL) in children, adolescents and young adults. On the premise of maintaining a 4-year event free survival (EFS)\>90% in the low-, intermediate-and high-risk groups, increase the early assessment complete response rate (the overall early complete response rate increased by 20%, that is, from 54.0% to 74.0%) to further reduce the proportion of children receiving radiotherapy to benefit them.

A Study of Pembrolizumab (MK-3475) in Pediatric Participants With an Advanced Solid Tumor or Lymphoma (MK-3475-051/KEYNOTE-051)

Researchers are looking for new ways to treat children with different types of melanoma (skin cancer), solid tumors, and lymphomas (blood cancers) that are any of these: * Advanced, which means cancer spread in the body or cannot be removed with surgery * Relapsed, which means cancer has come back after it had responded to previous treatment (responded means it stopped growing, gets smaller, or disappeared) * Refractory, which means cancer did not respond to previous treatment Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Researchers want to learn if different doses of pembrolizumab can cause at least 1 of the types of cancer to get smaller or go away. With Amendment 8, enrolment of participants with solid tumours and participants 6 months to under 12 years old with melanoma were closed. Enrolment of participants 12-18 years old with melanoma continues. Enrolment of participants who have tumours with specific traits (microsatellite-instability-high (MSI-H), and tumour-mutational burden-high ≥10 mutation/Mb (TMB-H)) also continues.

Ibrutinib and Nivolumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

This phase II trial studies how well ibrutinib and nivolumab work in treating patients with classical Hodgkin lymphoma that has come back or has not responded to treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Giving ibrutinib and nivolumab may work better in treating patients with classical Hodgkin lymphoma.

Camrelizumab Combined With AVD in the First-line Treatment for Patients With Advanced Classical Hodgkin's Lymphoma

This is a prospective single-arm, multi-center and phase II clinical trial to observe the efficacy and safety of Camrelizumab combined with AVD in the first-line treatment for patients with advanced classical Hodgkin's lymphoma.

European Project for ctDNA Detection as a Biomarker for Non-invasive Therapy Monitoring in Paediatric Classical Hodgkin Lymphoma

Classical Hodgkin lymphoma (cHL) accounts for 15% of all cases of cancer in children and adolescents and represents the first cause of cancer during adolescence. Combined multi-modal chemotherapy and modern radiation techniques have transformed cHL in a highly curable cancer. However, up to 10-15% of patients still experience recurrent or primary refractory disease. Thus, there is an unmet need for unravelling the underlying mechanisms of treatment failure and refractoriness in paediatric cHL. Further refinements of treatment strategy are still needed to improve treatment results both in relapse and refractory (R/R) patients and to reduce long-term morbidity and mortality treatment related. Therefore, two main objectives arise: to improve early detection of patients with a high relapse risk to potentially intensify the first line treatment and to better identify low risk patients to further reduce the treatment burden in this good-prognostic population. Initial disease stratification and long-term outcome predictions remain a challenging issue in the field. PET/CT is currently the reference imaging method for initial staging and improves detection of extra nodal disease. None of previous prognostic factors accurately identify patients who will respond adequately and therefore limit the ability to identify patients who should require treatment that is more intensive or new therapeutic approaches like immunotherapy. Taken together, these data emphasize a clear unmet need in the field of cHL. We aim to develop a biomarker tool, which could sharpen the initial risk stratification, improve the assessment of disease evaluation during the treatment and beyond and facilitate the detection of relapse. Over the past decade, as in other malignancies the potential of quantification of circulating tumour DNA (ctDNA) or liquid biopsy, in circulating cell-free DNA (cfDNA) that comprises DNA fragments released from apoptotic or necrotic cells into circulation, has emerged as a promising tool for diagnosis and exploration of the genetic landscape associated with HRS and for response evaluation. Experiences of ctDNA in cHL was first reported in adult cHL. These previous studies paved the way for ctDNA implementation in cHL. First, they contributed to confirm the feasibility to use ctDNA in the detection of tumor-associated mutation. Using paired samples of ctDNA and tumor DNA from HRS cells obtained by microdissection they confirmed the consistent correlation between these two methods. Second, they highlighted the potential role of ctDNA as a surrogate marker for tumor baseline assessment and more importantly for interim evaluation reporting an excellent correlation between the PET/CT result and the presence or the absence of ctDNA after 2 cycles of chemotherapy. Furthermore, Sobesky et al. previously reported that cured patients who were inconsistently judged as interim PET/CT-positive had a more than 2-log drop in ctDNA, whereas relapsing patients who were inconsistently judged as interim PET/CT negative had a less than 2-log drop in ctDNA. These data suggest that ctDNA could be a relevant adjunct to conventional PET/CT approach.

A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies

CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in participants with select blood cancers that have not responded to treatment with standard therapies or who have relapsed after treatment. The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body), immunogenicity (development of antibodies against the drug), and preliminary anti-cancer effect of MGD024. Participants will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met. Response assessments will be performed after Cycle 1 and then after every even numbered cycle starting with Cycle 2 until progression or study treatment discontinuation. Participants will be checked for side effects throughout the study.

Lifestyles Implemented-Survivorship Care Plan In Lymphoma Survivors

This is a prospective randomized open-label, multicenter, 2-arm study to assess the role of healthy LifeStyle implemented Survivorship Care Plan (LS-SCP) in modifying the Quality of Life (QoL) in a population of long-term lymphoma survivors (in remission for a minimum 3 years since the last treatment and a maximum of 10 years).

Allogeneic CD30.CAR-EBVSTs in Patients With Relapsed or Refractory CD30-Positive Lymphomas

This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study. In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins. The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients

Changing Paragidms In The Prognostic Assessment Of Hodgkin Lymphoma

Classical Hodgkin's Lymphoma (cHL) is a rare but highly treatable malignancy of the immune system, primarily affecting young adults. Despite significant therapeutic advancements, frontline treatment failure occurs in up to 30% of cases, with relapse or refractory disease affecting over 50% of these patients. The main therapeutic challenge in cHL remains achieving an optimal balance between disease control and reducing long-term adverse effects. Current prognostic tools only partially capture patient heterogeneity, and cHL continues to evolve spatially and temporally throughout the course of the disease. Personalized treatment strategies require novel integrated tools that better monitor tumor complexity and anticipate disease progression. Fluorodeoxyglucose positron emission tomography (FDG-PET) has improved risk stratification in cHL, as metabolic response during or after chemotherapy strongly correlates with disease progression and survival. However, FDG-PET has limitations, including the absence of standardized criteria and the necessity to initiate treatment before response assessment. To overcome these limitations, molecular profiling and radiomic analysis of baseline FDG-PET data may provide deeper insights into tumor biology, improving prognostic accuracy. This observational study aims to dissect the genetic and phenotypic heterogeneity of cHL at diagnosis and during disease evolution, with the goal of identifying novel prognostic biomarkers. These findings could lead to better treatment personalization, increasing cure rates while minimizing treatment-related toxicity. The study is based on the hypothesis that correlating DNA profiling at diagnosis, gene expression, and radiomic features may enable the identification of high-risk signatures, refining prognostic models in cHL. Additionally, liquid biopsy represents a non-invasive method for assessing tumor mutational complexity. The analysis of circulating DNA (cDNA) throughout disease progression could provide insights into genetic evolution and help predict overt progression before clinical manifestations occur. The primary objective is to define the genetic mutational profile of cHL at disease progression. As secondary objectives, it will evaluate whether liquid biopsy can accurately recapitulate the genetic heterogeneity observed in tumor tissue, determine the predictive accuracy of liquid biopsy in anticipating disease progression, and correlate genomic and radiomic features with patient outcomes to refine risk stratification and therapeutic decision-making. By integrating molecular and imaging-based biomarkers, this study aims to enhance personalized treatment strategies, improve risk-adapted therapeutic approaches, and ultimately optimize curability and quality of life for patients with cHL.

Itacitinib + Everolimus in Hodgkin Lymphoma

This is an open-label, single-group, Phase I/II study of itacitinib in combination with everolimus in subjects with relapsed or refractory classical Hodgkin lymphoma (cHL).

Phase II Trial of Anti-PD-1 Antibody Treatment and Radiotherapy in Early-stage Favorable Classic Hodgkin Lymphoma

By the implementation of the anti-PD-1 antibody pembrolizumab and given its possible synergy with RT, the aim of the present trial is to develop a chemotherapy-free first-line treatment for patients with newly diagnosed early-stage favorable cHL.

Abscopal Effect of Radiotherapy and Nivolumab in Relapsed Hodgkin Lymphoma After Anti-PD1 Therapy

The aim of the trial is to improve efficacy of nivolumab in patients with relapsed or refractory HL who recently progressed on anti-PD1 therapy. Nivolumab is highly effective and well tolerated in rrHL, nevertheless CR-rates are low and a considerable proportion of patients suffers from progressive disease. Localized RT induces an immunogenic effect which might work synergistically and facilitate augmented systemic (i.e. abscopal) responses in combination with nivolumab.

Sintilimab Plus AVD in Pediatric Low/Moderate Risk Hodgkin Lymphoma: A Phase II Study

Study Purpose: To evaluate the efficacy and safety of sintilimab in combination with AVD chemotherapy for the treatment of pediatric and adolescent patients with low-to-intermediate risk classical Hodgkin lymphoma (cHL). Study Design: This is a prospective, single-arm, multicenter, phase II clinical trial. Study Population: Pediatric and adolescent patients aged 1 to 18 years, diagnosed with classical Hodgkin lymphoma, and classified as low-to-intermediate risk according to the Ann Arbor staging system. Treatment Plan: Sintilimab in combination with AVD chemotherapy, administered every two weeks for a planned 4-6 cycles.

Phase 1 Study of CK-301 (Cosibelimab) as a Single Agent in Subjects With Advanced Cancers

CK-301 (cosibelimab) is a fully human monoclonal antibody of IgG1 subtype that directly binds to Programmed Death-Ligand 1 (PD-L1) and blocks its interactions with the Programmed Death-1 (PD-1) and B7.1 receptors. The primary objectives of this study are to assess the safety, tolerability and efficacy of CK-301 when administered intravenously as a single agent to subjects with selected recurrent or metastatic cancers.

CD30 CAR T-cells Post AutoHSCT for Poor-risk Hodgkin Lymphoma

Patients with poor risk classical Hodgkin Lymphoma (cHL) will undergo myeloablative chemotherapy (MAC) with autologous stem cell transplantation (AutoHSCT) and subsequently receive autologous CD30+ CAR T-cells.

Pembrolizumab in Combination With Salvage Chemotherapy for First-relapsed or Refractory Classical Hodgkin Lymphoma

The aim of this trial is to develop an effective and well-tolerated regimen for treatment of r/r cHL by introducing the anti-PD-1 antibody pembrolizumab and adding it to well-established chemotherapy regimens (ICE, DHAP). Synergistic effects of conventional agents with checkpoint inhibition may facilitate a highly effective therapy with limited toxicity, which might eventually substitute the very toxic high-dose chemotherapy (HDCT).

Phase II Trial of Individualized Immunotherapy in Early-Stage Unfavorable Classical Hodgkin Lymphoma

The aim of the trial is to establish an individualized first-line treatment incorporating checkpoint inhibition for early-stage unfavorable cHL, which is effective and well tolerated.

Fitness-adapted, Pembrolizumab-based Therapy for Untreated Classical Hodgkin Lymphoma Patients 60 Years of Age and Above

This is a multi-center, open-label phase II study to assess the efficacy of a novel fitness-adapted regimen in previously untreated older patients with classical Hodgkin lymphoma. All participants will receive up to a total of 8 cycles of pembrolizumab (Q6 week dosing). The first cycle of pembrolizumab will be administered in combination with brentuximab vedotin (BV) ("lead-in treatment"). Following lead-in treatment, all participants will undergo interim PET/CT (iPET) as well as fitness testing to help inform participant level of fitness for subsequent lymphoma-directed therapies. Participants deemed "Frail" by this assessment will continue 3 additional 6 week cycles of concurrent pembrolizumab and BV ("induction therapy", each cycle is 42 days), then continue single-agent pembrolizumab to complete up to 4 additional cycles (i.e., 8 total) of therapy ("consolidation and maintenance therapy", Frail cohort). Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5. Those deemed "fit" after lead-in therapy (Fit cohort) will continue pembrolizumab and switch from BV to concurrently-administered combination chemotherapy using doxorubicin (A), vinblastine (V), and dacarbazine (D) for a total of 4 planned AVD cycles (3, 6-week pembrolizumab cycles, "induction therapy"). Chemotherapy drugs will be given at standard doses as in ABVD (no bleomycin will be given in this study) on days 1 and 15 of each 28-day cycle (C1AVD), and pembrolizumab dosing will remain every 42 days. Following end-induction PET/CT, pembrolizumab will continue every 42 days for up to 4 cycles in the consolidation/maintenance phase. Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5. Participants deemed "unfit" after lead-in therapy and by fitness assessment will continue pembrolizumab and switch from BV to concurrently administered combination chemotherapy termed "mini-avd" as induction therapy. Mini-avd consists of lower doses of conventional AVD chemotherapy (doxorubicin, vinblastine and dacarbazine) and will be administered for on days 1 and 15 of a 28 day cycle for 4 planned cycles. Pembrolizumab will continue every 42 days. Following end-induction PET/CT, pembrolizumab will continue every 42 days for up to 4 cycles in the consolidation/maintenance phase. Two additional BV doses will be given as consolidation, at days 1 and 22 of pembrolizumab cycle 5.

HD21 for Advanced Stages

Primary objective of the trial is to demonstrate non-inferior efficacy of six cycles of BrECADD compared to six cycles of escalated BEACOPP, each followed by radiotherapy to PET-positive residual lesions ≥2.5 cm, in terms of progression free survival (efficacy objective). If non-inferior efficacy can be shown, the co-primary objective is to further demonstrate reduced toxicity of the BrECADD treatment compared to the escalated BEACOPP treatment measured by treatment related morbidity (TRMorbidity objective).

Study of Pembrolizumab With Bendamustine in Hodgkin Lymphoma

This is a phase 2 open-label study to test the safety and effectiveness of combining pembrolizumab and bendamustine in patients with relapsed (cancer that has come back or started getting worse) or refractory (cancer that is not responding or has stopped responding to treatment) Hodgkin lymphoma.

A Study of Zimberelimab(GLS-010) Combined With AVD for Newly Diagnosed Early-stage Hodgkin's Lymphoma

This is a multicenter, open-label single-arm phase II study to evaluate the efficacy and safety of Zimberelimab (GLS-010) combined with AVD for newly diagnosed early-stage Hodgkin's lymphoma under the guidance of PET/CT.

Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy

This is a Phase 1b, multicenter, open-label, single arm study to evaluate the safety and efficacy of the combination therapy, CD30.CAR-T and the programmed cell death protein-1 (PD-1) checkpoint inhibitor, nivolumab, in patients aged 12 years of age and above with relapsed or refractory classical Hodgkin lymphoma (cHL) following failure of standard frontline therapy.