Pembrolizumab

This study will assess the safety and efficacy of VS-7375 alone and in combination in patients with advanced solid tumors harboring a KRAS G12D-mutation.

This is a Phase II clinical study for people with stage IV cancer. The study will evaluate the use of stereotactic body radiation therapy (SBRT), a type of focused radiation treatment, together with immunotherapy-based treatment. SRBT will be used to treat multiple areas of cancer that have spread to other parts of the body. The study will evaluate whether this treatment approach can be safely given while patients continue their planned cancer treatment and may help control their cancer.

The purpose of this study is to see if people prefer immunotherapy treatment for kidney cancer delivered intravenously or subcutaneously and if it is practical for participants to receive labs at home and have a video (telehealth) visit with their doctor prior to their day of treatment.

This is a single-arm, phase II study of neoadjuvant combination therapy of Androgen Deprivation Therapy (ADT), \[Gonadotropin-Releasing Hormone (GnRH) agonist Leuprolide\], androgen receptor (AR)-antagonist Darolutamide and Pembrolizumab in a stratified high-risk localized prostate cancer cohort, followed by adjuvant treatment with Pembrolizumab (12 cycles) post-radical prostatectomy (RP). Patients with National Comprehensive Cancer Network (NCCN) high-risk non-metastatic prostate cancer (localized or locally advanced) (defined as Gleason ≥8, disease stage \>=cT3a, or PSA l \>20 ng/mL) will be risk-stratified at a biopsy using Decipher, a commercial standard-of-care diagnostic assay. Patients satisfying all three criteria of high-risk genomic characteristics listed below as per the Decipher grid results will be enrolled in the study: 1. Decipher Genomic classifier, GC\>0.6 2. AR activity score/AR-output gene signature (ARoS)\>11.0 3. High Luminal B score/ PAM50 subtype signature

The investigational drug to be studied in this protocol, BCA101, is a first-in-class compound that targets both EGFR with TGFβ. Based on preclinical data, this bifunctional antibody may exert synergistic activity in patients with EGFR-driven tumors.

The goal of this clinical trial is to evaluate the safety of the combination therapy of Lutetium (177Lu) DGUL and pembrolizumab. It will also assess the antitumor efficacy and pharmacokinetics of the combination therapy compared to Lutetium (177Lu) DGUL monotherapy. Participants will: Monotherapy: Receive Lutetium (177Lu) DGUL 4 times (plus 2 additional doses) at 6-week intervals Combination therapy: Receive Lutetium (177Lu) DGUL 4 times (plus 2 additional doses) at 6-week intervals along with pembrolizumab up to 18 times at 6-week intervals

This phase II trial compares the effect of GI-102 alone and in combination with pembrolizumab given before surgery in treating patients with IDH wildtype glioblastoma and IDH mutated grade 4 astrocytoma that has come back after a period of improvement (recurrent) or that is growing, spreading, or getting worse (progressive). Glioblastoma is the most common and the most aggressive primary brain tumor in adults. Current standard of care includes surgical resection, radiation and chemotherapy. Treatment is often given before surgery (neoadjuvant therapy) to shrink the tumor and make it easier to remove. Treatment with GI-102, a bispecific fusion protein, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving GI-102 alone and in combination with pembrolizumab between neoadjuvant therapy and surgery may be safe, tolerable, and effective in treating patients with recurrent or progressive IDH wildtype glioblastoma and IDH mutated grade 4 astrocytoma.

This phase IV trial tests the impact of standard of care enfortumab vedotin and pembrolizumab followed by removal of all or part of the bladder (cytoreductive cystectomy) and/or removal of all or part of the tube that carriers urine from the kidneys to the bladder (ureterectomy) on outcomes in patients with bladder and upper urothelial tract that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). 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. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Giving standard of care enfortumab vedotin and pembrolizumab followed by cytoreductive cystectomy and/or ureterectomy (CC/U) may improve outcomes in patients with locally advanced or metastatic bladder or upper urothelial tract cancer.

This phase Ib/II trial studies the side effects, best dose, and effectiveness of enfortumab vedotin (EV) in combination with pembrolizumab and radiation therapy for treating patients with muscle invasive bladder cancer. Standard of care treatment for muscle invasive bladder cancer is chemotherapy, to shrink the tumor before the main treatment is given (neoadjuvant), followed by surgery to remove all of the bladder as well as nearby tissues and organs (radical cystectomy). In cases where patients are not candidates for the standard of care approach or prefer a bladder sparing option, tri-modality therapy with transurethral resection of bladder tumor (TURBT) followed by combined chemotherapy and radiation therapy is used. 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. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving enfortumab vedotin with pembrolizumab and radiation therapy may work better in treating patients with muscle invasive bladder cancer.

This study evaluates the impact of neoadjuvant Programmed cell death Protein 1 (PD-1)-based treatment regimens in patients with resectable stage IIIB-M1a cutaneous or unknown primary melanoma at high risk of relapse without adjuvant therapy after definitive lymphadenectomy and irrespective of pathologic response outcome on the 2-year overall survival (OS). It was hypothesized that neoadjuvant PD1 inhibitor-based treatment without adjuvant treatment does not significantly (non-inferior) impact OS in this study patient population. Patients will be randomized to either two infusions of pembrolizumab or one infusion of ipilimumab plus nivolumab followed by a single infusion of nivolumab. Patients will undergo follow-up and restaging scans to assess event-free survival at 12 months and OS at 24 months after the first neoadjuvant treatment infusion.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with an annual incidence of approximately 700,000 cases. This study aims to evaluate the change in disease activity and optimal dose, and optimal dose of telisotuzumab adizutecan in combination with pembrolizumab as first-line treatment in participants with recurrent or metastatic head and neck squamous cell carcinoma. Telisotuzumab adizutecan is an investigational drug being developed for the treatment of recurrent or metastatic HNSCC. Participants are placed into 3 treatment groups called treatment arms. Each group receives a different treatment. Adult participants diagnosed with recurrent or metastatic HNSCC who have not received prior systemic therapy for advanced disease and whose tumors express c-Met protein will be enrolled. Approximately 180 participants will be enrolled in the study at sites worldwide. Participants will receive intravenous doses of telisotuzumab adizutecan with intravenous pembrolizumab, or standard of care (SOC) chemotherapy with pembrolizumab. Participants will receive treatment as part of a 67 weeks study duration. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits every 3 weeks during the study at a hospital or clinic. The effects of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Anti-PD-1 monotherapy has demonstrated significant clinical efficacy in advanced or metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression (tumor proportion score \[TPS\] \>50%), outperforming platinum-based chemotherapy in terms of objective response rate (ORR) and overall survival (OS). Pivotal randomized trials such as KEYNOTE-024 and EMPOWER-Lung 1 established the superiority of PD-1 blockade in this patient population, leading to regulatory approvals by both the FDA and EMA for first-line treatment. These studies confirmed that a subset of patients can achieve deep and durable responses with immunotherapy alone, highlighting the potential of immune checkpoint inhibition to provide long-term clinical benefit without the toxicities associated with cytotoxic chemotherapy. Despite these successes, accumulating clinical evidence has revealed a clinically significant risk of hyperprogressive disease (HPD) in a subset of patients treated with anti-PD-1 monotherapy. HPD is characterized by an unexpected and rapid acceleration of tumor growth following treatment initiation and is associated with early clinical deterioration and increased mortality. This phenomenon likely contributes to the early crossover of survival curves frequently observed when comparing immunotherapy alone with chemotherapy in first-line NSCLC trials. In contrast, such early survival crossover is not observed in trials comparing chemotherapy-immunotherapy combinations with chemotherapy alone, including CheckMate-227, CheckMate-9LA, KEYNOTE-189, and KEYNOTE-407. These results have led many thoracic oncologists to favor combined chemo-immunotherapy regimens as first-line treatment, as they reduce the risk of HPD and increase initial ORR. However, while chemotherapy combined with immunotherapy effectively mitigates the risk of hyperprogression and improves early response rates, it also appears to compromise the durability of antitumor immune responses. Clinical data indicate that the median duration of response with chemo-immunotherapy combinations is approximately 10-11 months, compared with more than 22 months for anti-PD-1 monotherapy alone. This difference is likely attributable to the cytotoxic effects of chemotherapy on immune effector cells, which may limit the persistence and depth of immune-mediated tumor control. Consequently, there remains a strong clinical need to identify patients who could safely and effectively benefit from anti-PD-1 monotherapy while avoiding unnecessary exposure to chemotherapy. Multiple early-phase translational studies have independently identified soluble plasma biomarkers associated with response or resistance to PD-1 blockade in advanced NSCLC. Building on this body of evidence, translational analyses conducted at Gustave Roussy Cancer Center have identified a composite signature of circulating soluble factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), soluble CD14 (sCD14), soluble CD25 (sCD25), and growth differentiation factor-15 (GDF-15). Together, these biomarkers define a Pro-Tumoral Inflammation (PTI) signature that is strongly associated with primary resistance to anti-PD-1 monotherapy. Elevated PTI scores reflect a systemic inflammatory state that promotes tumor progression and immune dysfunction, and have been linked to poor clinical outcomes, including non-response and hyperprogressive disease. Within the META-1 sub-protocol of the METAREM master protocol, the investigators propose to integrate these soluble biomarkers into a single PTI score generated through baseline PORTRAIT immunoprofiling. The primary objective of this approach is to prospectively validate the predictive value of the PTI score for anti-PD-1 monotherapy efficacy in advanced NSCLC. By enabling early identification of patients at high risk of resistance or hyperprogression, this strategy aims to refine patient stratification and guide first-line treatment selection. Ultimately, the use of the PTI score could allow clinicians to identify patients most likely to benefit from anti-PD-1 monotherapy, preserving the potential for durable responses while sparing others from ineffective treatment and optimizing the overall therapeutic strategy in advanced NSCLC.

In this study we are evaluating the safety and feasibility of the triple combination (TTFields, MLA, pembrolizumab) in adult patients diagnosed with recurrent or progressive glioblastoma (GBM) WHO Grade IV, IDH wild type or recurrent or progressive astrocytoma WHO grade IV.

The purpose of this study is to evaluate the efficacy and safety of Disitamab Vedotin combined with Trastuzumab and Tislelizumab Versus Chemotherapy Combined with Trastuzumab with or without Pembrolizumab as First-Line Treatment for Advanced Gastric/Gastroesophageal Junction Adenocarcinoma with HER2-high Expression.

The purpose of this study is to assess the safety/tolerability/feasibility of pembrolizumab and radiation therapy before surgical resection in patients with recurrent glioblastoma as defined by treatment-related AEs and the number of patients who do not necessitate a delay in surgical resection, and to assess overall survival. The secondary objectives are to assess progression free survival, and to assess the T cell clonality, CD8 T cell activation and Tumor Infiltrating Lymphocyte (TIL) score after treatment

This study will test whether enfortumab vedotin combined with pembrolizumab is an effective treatment for people with bladder cancer (urothelial carcinoma) involving the lymph nodes who are going to have surgery to remove their cancer (cystectomy). The researchers will look at whether treatment with enfortumab vedotin and pembrolizumab before surgery can get rid of cancer within the lymph nodes. They will also try to find out if this combination of drugs is effective at shrinking participants' cancer before their surgery. The researchers think that a combination of enfortumab vedotin and pembrolizumab may help people with this disease because both drugs are designed to help the immune system attack and kill cancer cells. The researchers think the drugs may be more effective if given in combination rather than on their own.

This phase Ib/II trial tests the safety, side effects, and best dose of quemliclustat in combination with enfortumab vedotin and pembrolizumab, and to see how well the combination works for the treatment of bladder, renal pelvis, or ureter urothelial cancer that cannot be removed by surgery (unresectable), that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). 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 cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Quemliclustat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving quemliclustat in combination with enfortumab vedotin and pembrolizumab and may be safe, tolerable and/or effective in treating patients with unresectable locally advanced and metastatic urothelial cancer.

This is a phase II, two-arm, noncomparative screening study of Sacituzumab tirumotecan, an intravenous antibody-drug conjugate (ADC) that targets Trop-1, administered alone or in combination with pembrolizumab, a monoclonal antibody to PD-1 in patients with relapsed clear cell cancers that originated in the ovary, fallopian tube or peritoneal cavity, inclusive of endometriosis (collectively referred to as OCCC throughout the protocol) after previous treatment with anti-PD1 therapy. The regimens will be evaluated separately, and the study is not designed or powered to compare the regimens.

Phase I Part : Confirm the safety of GAIA-102 as a monotherapy or GAIA-102 and pembrolizumab in combination for advanced gastrointestinal cancer of microsatellite stable with malignant ascites, and determine the recommended number of doses for Phase II part. Phase II Part(Gastric Cancer):Comparative Study Research the efficacy and safety of as a monotherapy or GAIA-102 and pembrolizumab for advanced gastrointestinal cancer of microsatellite stable with malignant ascites at the recommended dose of GAIA-102 decided in the Phase I part. Phase II Part (Pancreatic Cancer): Comparative Study Including a Run-in Cohort Research the efficacy and safety of a combination regimen of GAIA-102 and pembrolizumab added to existing chemotherapy (standard of care) for microsatellite stable advanced pancreatic cancer with malignant ascites at the recommended dosing frequency of GAIA-102 decided in the Phase I part.

This study is designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary efficacy following oral administration of AZD3470 as a monotherapy, and in combination with other anticancer agents in participants with haematologic malignancies.

This is a single-center, open-label, study of Prostate-Specific Membrane Antigen (PSMA)-targeted radionuclide therapy with 177Lu-PSMA-617 in combination with pembrolizumab in participants with metastatic castrate-resistant prostate cancer (mCRPC) who have previously progressed on at least one prior androgen pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide).

This is a phase II trial of combination therapy of pembrolizumab and lenvatinib in patients with locally advanced or metastatic cervical cancer that had failed first line of therapy. The hypothesis is the combination of lenvatinib and pembrolizumab will overcome vascular endothelial growth factor (VEGF)-mediated immunosuppression to enhance the response of patients with locally advanced or metastatic cervical cancer.

This is an early development study of ASP388B in people with solid tumors. In this study, ASP388B will be given to people for the first time. It will be given by itself or together with standard cancer therapies. The main aims of the study are to check the safety of ASP388B and find the most suitable dose. This study will be in 2 parts. In Part 1, different small groups of people with solid tumors will receive lower to higher doses of ASP388B. Some groups will receive ASP388B by itself, and other groups will receive ASP388B with standard cancer therapies. Any medical problems will be recorded for each dose. This is to find suitable doses of ASP388B to use in Part 2 of the study, and to include the tumor types that responded well to ASP388B. In Part 2, other different small groups of people with the specific tumor types (from Part 1) will receive the most suitable doses worked out from Part 1. Some groups will receive ASP388B by itself, and other groups will receive ASP388B with standard cancer therapies. In both parts of the study, ASP388B will be given once in 3-week cycles. The standard cancer therapies will be given according to their approved label. ASP388B and the standard cancer therapies will be given slowly through a tube into a vein. This is called an infusion. In both parts of the study, safety checks will be done at each visit, and the doctors will continue to check for medical problems throughout the study.

This is a multicenter, open-label, Phase II clinical study to assess the efficacy, safety, tolerability, PK characteristics, and immunogenicity of SKB571 in participants with recurrent or metastatic HNSCC.

A first in human study to evaluate the safety and preliminary antitumor activity of BBO-8520, a KRAS G12C (ON and OFF) inhibitor, as a single agent and in combination with pembrolizumab and BBO-10203 in subjects with locally advanced and unresectable or metastatic non-small cell lung cancer with a KRAS (Kirsten rat sarcoma) G12C mutation.