Lenvatinib

This study will evaluate whether adding MRG003 to an ongoing treatment regimen can produce confirmed tumor shrinkage in patients with EGFR-positive advanced thyroid cancer whose cancer initially benefited from that regimen and later progressed. The study will also evaluate the safety of the combinations. Cohort A will include patients with anaplastic or poorly differentiated thyroid carcinoma who previously benefited from lenvatinib plus an anti-PD-1 inhibitor and subsequently progressed. They will continue lenvatinib and the same anti-PD-1 inhibitor, with MRG003 added. Cohort B will include patients with radioactive iodine-refractory differentiated thyroid carcinoma who previously benefited from lenvatinib and subsequently progressed. They will continue lenvatinib, with MRG003 added. MRG003 will be given intravenously at 2.0 mg/kg every 3 weeks. The study plans to enroll 39 participants: 24 in Cohort A and 15 in Cohort B. The first 3 participants in each cohort will undergo an initial 6-week safety assessment before further enrollment is allowed. If additional safety assessment is needed, up to 6 participants who can be evaluated for dose-limiting toxicity will be assessed within the planned cohort enrollment. The main outcome is the proportion of patients in each cohort whose tumors shrink or disappear within 12 weeks after MRG003 starts, with the response confirmed at least 4 weeks later and by Week 18. Scans obtained before MRG003 is added provide the new baseline. Disease control is assessed at Week 12. Other response and survival outcomes are followed for up to 12 months after MRG003 starts. Safety follow-up continues during study treatment and for 90 days after the last study treatment dose, with longer follow-up of unresolved events as needed.

To explore the efficacy and safety of cryoablation combined with hepatic arterial infusion of iparomlimab and tuvonralimab, intravenous dacarbazine, and oral lenvatinib in patients with liver metastases from malignant melanoma.

This prospective, non-randomized, concurrent parallel-controlled study will evaluate treatment response and resistance mechanisms in patients with pancreatic neuroendocrine tumors with liver metastases (pNET-LM) receiving second-line systemic therapy after failure of first-line treatment. Eligible patients will receive either lenvatinib combined with chemotherapy or chemotherapy alone according to the study protocol and clinical treatment strategy. The clinical efficacy and safety of the two treatment strategies will be evaluated using objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Peripheral blood samples will be collected before treatment, during early treatment, and at disease progression. Circulating cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMCs) will be analyzed to investigate molecular and immune changes associated with treatment response, primary resistance, and acquired resistance. The study aims to identify potential biomarkers for predicting treatment response and to improve understanding of resistance mechanisms in pNET-LM.

HCC is a common cancer worldwide and a leading cause of cancer-related death. Lung cancer is the most frequently diagnosed cancer in the world, and the leading cause of cancer deaths. The purpose of this study is to assess adverse events and change in disease activity when ABBV-324 is given to adult participants to treat hepatocellular cancer (HCC) or squamous-cell non-small cell lung cancer (LUSC). ABBV-324 is an investigational drug being developed for the treatment of HCC and LUSC. Study doctors put the participants in groups called arms. Each arm receives ABBV-324 alone (monotherapy) or a comparator drug, lenvatinib followed by a safety follow-up period. Approximately 232 HCC or LUSC will be enrolled in the study in approximately 45 sites worldwide. In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of ABBV-324 until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will receive ABBV-324, or a comparator of oral lenvatinib. The study will run for a duration of approximately 6.5 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 an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

Advanced hepatocellular carcinoma (HCC) remains a major therapeutic challenge. Although targeted therapy combined with immune checkpoint inhibitors has improved clinical outcomes, the objective response rate and conversion surgery rate remain suboptimal. Irreversible electroporation (IRE) is a non-thermal ablation technique that can induce tumor cell death while preserving surrounding vascular and biliary structures. Emerging evidence suggests that IRE may enhance anti-tumor immunity and synergize with systemic therapy. This prospective, single-center, open-label study aims to evaluate the efficacy and safety of IRE combined with lenvatinib and sintilimab in patients with advanced HCC. Eligible patients with unresectable CNLC stage IIa, IIb, or IIIa disease will receive standard targeted therapy and immunotherapy with or without IRE according to treatment allocation. The primary endpoints are objective response rate (ORR) and conversion surgery rate. Secondary endpoints include time to response (TTR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). The study is expected to provide evidence regarding the role of IRE in enhancing tumor response and increasing the likelihood of curative-intent surgical resection in patients with advanced HCC.

The purpose of this study is to learn how well a combination of iparomlimab and tuvonralimab (QL1706), lenvatinib, radiotherapy, and hepatic arterial infusion chemotherapy (HAIC) works and how safe it is for people with hepatocellular carcinoma (HCC) that has grown into the portal vein, forming a portal vein tumor thrombus (PVTT). Participants will receive iparomlimab and tuvonralimab together with lenvatinib, radiotherapy directed at the portal vein tumor thrombus, and HAIC, which delivers chemotherapy directly through the hepatic artery. Researchers will evaluate how long the cancer remains controlled without getting worse, how much the tumors shrink, how long participants survive, and whether the treatment makes surgery possible for some participants. Treatment-related side effects will also be assessed. The study will also explore whether features in tumor tissue and blood are associated with treatment response and may help identify patients who are more likely to benefit from this treatment strategy.

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-101/GI-101A as a single agent or in combination with pembrolizumab or lenvatinib over a range of advanced and/or metastatic solid tumors.

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 open-label, single-arm, phase 2 study evaluating hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and cadonilimab as conversion therapy for initially unresectable hepatocellular carcinoma (HCC). The primary objective is to assess the conversion rate, defined as the proportion of participants who are deemed amenable to curative-intent treatment by the multidisciplinary team (MDT), including R0 resection, curative ablation, or liver transplantation, after study treatment. Secondary objectives include curative-intent intervention rate, tumor response, survival outcomes, safety, pathological response, and exploratory tissue and blood biomarkers.

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.

This is a prospective, multicenter, randomized controlled, phase 3 study to explore the efficacy and safety of neoadjuvant tislelizumab plus lenvatinib in patients with resectable HCC at high risk of recurrence.

This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.

This is a Phase 2b, randomized, blinded clinical trial investigating the efficacy and safety of visugromab in combination with nivolumab and Lenvatinib compared to double placebo and Lenvatinib in participants with unresectable or metastatic HCC and compensated liver function (Child-Pugh A) after failure of 1L treatment that included an anti-PD-(L)1 compound. The trial consists of 2 Parts: a non-randomized Safety-run-in part (Part 1) and the subsequent randomized part (Part 2) with 2 treatment arms (A and B). Randomization of participants into Treatment Arm A and B will continue until 40 efficacy-evaluable participants are enrolled into each Treatment Arm.

The purpose of this study is to compare the effects on participants' and liver cancer by adding a drug that is used on its own to treat this disease to a combination of two other drugs which is also used to treat liver cancer, compared to the two-drug combination alone.

The purpose of this study is to test whether the combination of lenvatinib, pembrolizumab, and fulvestrant is a safe and effective treatment that causes few or mild side effects in people with ER+/HER2- metastatic breast cancer.

This is single arm study of a window of opportunity in which participants with previously untreated triple negative breast cancers (TNBC) who are candidates for potentially curative surgery will receive lenvatinib 12 mg daily for 7 and pembrolizumab 200 mg IV on day 1 prior to surgery

The primary objectives of the study are: (1) in the dose-escalation part: to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of farletuzumab ecteribulin (MORAb-202) in participants with selected tumor types (ovarian cancer \[OC\], endometrial cancer \[EC\], non-small cell lung carcinoma \[NSCLC\], triple-negative breast cancer \[TNBC\]), and (2) in dose-confirmation part: to evaluate preliminary efficacy measured by objective response rate (ORR) of farletuzumab ecteribulin (MORAb-202) in participants with OC and EC at selected doses and to further evaluate the safety and tolerability of farletuzumab ecteribulin (MORAb-202) and (3) dose-optimization part. (divided in two parts: Part A \[OC and EC participants\] and Part B \[OC only\]): Part A: to evaluate other farletuzumab ecteribulin (MORAb-202) treatment regimens for safety, tolerability and preliminary efficacy in participants with OC and EC; to evaluate the addition of short course of oral corticosteroids following every dose of farletuzumab ecteribulin (MORAb-202) administered every 21 days; and to select treatment regimens with farletuzumab ecteribulin (MORAb-202) for further evaluation in Part B. Part B: to evaluate the safety and tolerability of different doses of farletuzumab ecteribulin (MORAb-202) as monotherapy and in combination with lenvatinib and to determine the recommended dose (RD) of farletuzumab ecteribulin (MORAb-202) as monotherapy and in combination with lenvatinib.