View clinical trials related to Carcinoma, Non-Small-Cell Lung.
Filter by:This is a randomized phase II study assessing the activity of single agent chemotherapy combined with nivolumab (Arm A) compared to single agent chemotherapy alone (Arm B) in squamous or non-squamous NSCLC subjects with primary resistance to prior PD-1 or PDL-1 inhibitor. The single agent chemotherapy chosen is at the discretion of the site investigator and may include pemetrexed, gemcitabine or taxotere. Institutional standards should be used for administration of the single agent chemotherapy. For both treatment arms, 21 days equals 1 cycle of therapy and subjects will be eligible to continue treatment until progressive disease by RECIST v1.1 or unacceptable toxicity. Upon registration, subjects will be randomized in a 1:1 ratio to either treatment with single agent chemotherapy or single agent chemotherapy in combination with nivolumab. Randomization is un-blinded and open-label; therefore there will be no placebo treatment for subjects randomized to single agent chemotherapy
Lung cancer is still the leading cause of cancer related-deaths worldwide, with an overall all-stage 5-year survival of approximately 17%. The primary treatment of early stage (I-IIIA) NSCLC is curative surgery. Although patients treated with curative surgery have a better prognosis, the 5-year survival for patients treated with surgery alone remains low, ranging from 67% (stage IA) to 23% (stage IIIA). Several randomized trials comparing postoperative chemotherapy versus no chemotherapy have shown a significant overall survival benefit from postoperative chemotherapy in completely resected patients with NSCLC stage II and IIIA. Likewise other randomized trials have demonstrated preoperative chemotherapy improves survival and recently the analyses also based on individual patients data of 15 randomized trials showed a significant benefit of preoperative chemotherapy on survival with the same survival improvement of 5% at 5 years. Then, neoadjuvant chemotherapy has also become accepted in many countries. Targeting of PD-1 receptors and its ligand PD-L1, and inhibiting their engagement is an attractive therapeutic option in the early stage NSCLC, which may reactivate host immune responses and enable longterm tumor control.
The purpose of this study is to determine the feasibility and evaluate the safety of delivering chemoradiotherapy, the usual approach to non-small cell lung cancer, in combination with pembrolizumab (MK-3745), followed by consolidation pembrolizumab after surgical resection. Consolidation therapy is treatment given following the initial treatment. Pembrolizumab is an investigational drug (also known as Keytruda), which has been approved by the FDA for use in certain types of skin cancer (melanoma), and for use in certain types of head and neck cancer. However, it has not been approved for use in other cancers such as non-small cell lung cancer (NSCLC). Pembrolizumab is a monoclonal antibody that binds to the surface of some cells of the immune system and activates them against cancer cells. It is not chemotherapy.
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
Rationale: Completely resected non-small cell lung cancer (NSCLC) patients with histologically confirmed N2 disease are a heterogeneous population. After complete resection and postoperative chemotherapy (POCT), 20%-40% of cases have a risk of locoregional recurrence (LRR). Postoperative radiation therapy (PORT) should be an integral component of the multidisciplinary treatment for patients with stage IIIA(N2) disease. Postoperative Radiotherapy (PORT)-first strategy may have an advantage of the early administration of locoregional therapy to the mediastinum, in which the tumor burden is presumed to be higher than that of systematic micrometastases. It is not yet known for subsets with specific prognostic factors that confer higher LRR risks, what is the optimal timing of PORT and how to integrate with POCT (in a sequential fashion or concurrent fashion) when PORT is considered for patients with completely resected stage IIIA(N2) NSCLC. Purpose: This randomized phase III trial is studying the optimal timing of PORT to evaluate whether the PORT-first strategy (PORT administered first with concurrent or subsequent POCT) may be more effective than the PORT-last strategy (PORT administered sequentially following POCT) in treating high risk of LRR patients with completely resected pathologic stage IIIA(N2) NSCLC.
The optimal prioritization of second-line chemotherapy and immune therapy based on demographic or biomarker data is an area of ongoing investigation. The hypothesis of this study is that there may be an additive or synergistic antitumor effect of combined chemotherapy and nivolumab in the second-line treatment of NSCLC as an important concept to test in a clinical trial. Previously treated NSCLC remains a setting of unmet clinical need despite recent clinical research progress. Early progression for a subset of NSCLC patients receiving nivolumab is a specific area of clinical need.
For the phase I component of the trial a classic 3 + 3 dose escalation design will be utilized, with a fixed dose of pembrolizumab and an escalating dose of the lenalidomide. The patient population will all have histologically confirmed advanced solid tumor malignancy. The primary endpoint for the phase I component of this protocol will be determining the maximum tolerated dose (MTD) of lenalidomide in combination with pembrolizumab. The phase II component of this trial will utilize a two stage design, initially enrolling 13 patients, followed by 13 more patients if the early stopping criteria are not met. The target population will include patients with histologically confirmed diagnoses of non-small cell lung carcinoma, regardless of histologic subtype; who have completed one line of standard therapy. The primary endpoint for the phase II component of this protocol will be determining efficacy as measured by progression free survival (PFS)
The study is divided into two parts. The first part of the study will test various doses of ASN003 to find out the highest safe dose to test in three specific groups. The second part of the study will test how well ASN003 can control cancer. Subjects will be enrolled into one of three groups. Group 1: metastatic or recurrent melanoma with documented BRAFV600 mutation (n=20 evaluable patients) Group 2: metastatic colorectal cancer (CRC), or advanced non-small cell lung cancer (NSCLC) with documented BRAFV600 mutation (n=14 evaluable patients) Group 3: advanced solid tumors with documented PI3K pathway alterations (PIK3CA mutation or PTEN loss) (n=14 evaluable patients)
The study will evaluate the clinical activity of nivolumab in combination with 3 separate investigational agents, glesatinib, sitravatinib, or mocetinostat.
This study is being done to find out the side effects (unwanted effects) that are caused in patients with cancers who are given SGN-2FF. This study will also attempt to find the most suitable dose in the disease or condition being studied and look at other effects of SGN2FF, including its effect on cancer. This study has several different parts. Part A will try to find the highest safe dose. Part B will enroll more patients to be treated at the highest safe dose or a lower dose to better understand how well SGN-2FF is tolerated. Part C will try to find the highest safe dose of SGN-2FF when it is given combined with pembrolizumab. Pembrolizumab is a standard treatment for cancer. Part D will enroll more patients to be treated at the highest safe dose of SGN-2FF combined with pembrolizumab or a lower dose of SGN-2FF to better understand how well SGN-2FF is tolerated when it is given with pembrolizumab.