Active clinical trials for "Lung Neoplasms"

This phase I trial studies the side effects of atezolizumab, varlilumab, and radiation therapy in treating patients with non-small cell lung cancer that has spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). 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. Immunotherapy with monoclonal antibodies such as varlilumab may induce changes in body?s immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving atezolizumab, varlilumab, and radiation therapy may increase the amount of time the disease is not active or does not spread to another part of the body.

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in combination with Opdivo (nivilumab) for the treatment patients with of metastatic, advanced, or recurrent solid tumors. All participants will receive open-label AL3818 with nivolumab. Part 1 consists of a dose finding phase to determine the recommended phase 2 dosage of AL3818 with nivolumab. Part 2 consists of a dose expansion phase, evaluating the safety and efficacy of the combination in patients cohorts including metastatic, advanced, or recurrent soft tissue sarcomas, non-small cell lung cancer, and small cell lung cancer.

A Phase I/II study of autologous T cells engineered using the Sleeping Beauty transposon/transposase system to express TCR(s) reactive against neoantigens in subjects with relapsed/refractory solid tumors

This is a multicenter phase 2 clinical trial to investigate the treatment efficacy and feasibility of combining thoracic radiotherapy (TRT) with the IMpower133 regimen in the upfront treatment of ED SCLC patients. Patients with a response after induction therapy with carboplatin/etoposide and atezolizumab will be included into this study to subsequently receive atezolizumab maintenance therapy and will be randomized to receive TRT or not. This trial aims to i.) increase the efficacy of combined atezolizumab- and chemotherapy by adding radiotherapy and ii.) determine the safety and tolerability of the combination of chemotherapeutic, immunological and radiological treatment in the first-line setting of advanced SCLC, and iii.) to collect tumor tissue as well as blood and stool samples for separate biomarker research project.

Standard of care for Extensive-Stage Disease (ED) Small Cell Lung Cancer (SCLC) as first-line treatment is 4 to 6 cycles of platinum based chemotherapy (carboplatin or cisplatin) in combination with etoposide. However, the outcome of the disease remains poor with a median overall survival of approximately 10 months, mainly caused by rapid development of drug resistance. The risk of intrathoracic recurrences can be reduced and an improved 2-year survival can be achieved with the addition of thoracic radiotherapy (tRT). The main objective of the trial is to evaluate the efficacy of tRT combined with maintenance durvalumab in SCLC after chemoimmunotherapy. Secondary objective is to evaluate the safety of tRT combined with maintenance durvalumab in SCLC after chemo-immunotherapy. For this trial durvalumab is the IMP. Patients will start with an induction phase (part 1): Patients will receive durvalumab in combination with carboplatin and etoposide for 4 cycles of 21 days. Patients with CR; PR or SD after the induction phase, will transfer to the maintenance phase (part 2): Patients will receive durvalumab treatment up to PD or max. 2 years, i.e. 26 maintenance cycles, in combination with tRT. Patients with PD after the induction phase will transfer to the follow-up phase: Patients will be followed up for 24 months, every 8 weeks.

Phase 1b/Phase 2 Umbrella Study; open-label, multi-center, parallel group study. Sasanlimab (a PD-1 antagonist monoclonal antibody) will be combined with a different targeted therapy in each sub-study. Phase1b of each sub-study will evaluate the safety of the combination and select the dose for the Phase 2 portion. Phase 2 of each sub-study will evaluate the anti-tumor activity of the combination. Sub-Study A is active, not recruiting, ongoing participants are still receiving treatment in Phase 1, Phase 2 will not be initiated. Sub-study B remains active, not recruiting, ongoing participants are still receiving treatment.

Radiotherapy (RT), at a total dose of 60-66 Gy over 6 weeks, combined with platinum-based chemotherapy, is the standard of care for stage III Non-Small Cell Lung Cancers (NSCLC) patients with unresectable or inoperable disease. However, the long-term outcomes are poor, with a 5-year overall survival (OS) rate of 15-35% for stage IIIA, and 5-10% for stage IIIB patients. The recent association of immunotherapy has been proven to improve Progression Free Survival (PFS) and OS for these patients and durvalumab consolidation following chemoradiotherapy (CT-RT) is now the new standard of care. Compared to older technics (2Dimensions(D) and 3D-RT), intensity-modulated radiotherapy (IMRT) allows for improved organs-at-risk sparing, owing to the high dose conformation to the target volume, thus reducing toxicity rates. In regard to the recent results of adjuvant immunotherapy, the benefits of concomitant chemotherapy with radiotherapy could be re-evaluated. With the changing landscape in the standard treatment of Local Advanced NSCLC (LA-NSCLC), the reduction in treatment-induced toxicity, while maintaining optimal tumor control, has become a priority, thereby warranting access to adjuvant immunotherapy for these patients. Due to the toxicity of the chemoradiotherapy, a large subset of patients may be unfit for the adjuvant immunotherapy. The use of immunotherapy concomitant to radiotherapy without chemotherapy may be the next step. Nevertheless, as immune cells are highly sensitive to conventional RT doses, the paradigm of the standard irradiation volumes should be reconsidered. In this context, the introduction of IMRT to spare lymphatic tissues and bone marrow deserves evaluation in prospective trials. A strong body of evidence supports the combination of RT with immunotherapy such as a Programmed cells Death-1 (PD1) inhibitor. Radiation alone can modify the immune response in several ways to allow for synergistic effects when combined with immunotherapy. The reduction in treatment-induced toxicity while maintaining optimal tumor control has become a priority, thereby warranting access to adjuvant immunotherapy for these patients. In this context, the introduction of IMRT to spare lymphatic tissues and bone marrow deserves evaluation in prospective trials. The timing of administration of immunotherapy seems to be a major point. Previous data in mice showed that an improved survival benefit with concurrent anti-PD-Ligand1 (PD-L1) and RT versus sequential administration. Moreover, for sequential schedule, an improved survival outcome was found for patients receiving first dose of durvalumab within 14 days of last radiotherapy fraction compared to 14 days or greater. Furthermore, immunotherapy combined with radiotherapy appears to be safe, without increase of the toxicity. In summary, there is a strong rationale for testing this new paradigm of accelerated IMRT combined with concurrent and maintenance nivolumab for locally advanced non-small lung cancer, due to: The unmet medical need for new Standard Of Care (SOC) better tolerated and " as " or " more " effective treatment than CT-RT The need to decrease radiation-induced toxicity The limit of CT-RT followed by durvalumab consolidation, leading to a high rate of recurrence within the 18 months (18-month PFS rate of 44.2%) The strong rationale to combine RT and PD-1 inhibition It is hypothesized this innovative concept to be safe in the context of this study for the following reasons: The use of moderate accelerated intensity-modulated radiotherapy (H-IMRT) allows decreasing both the Overall Treatment Time (OTT) and the dose to the organs at risk The decrease of the OTT (24 fractions instead of 33 fractions) combined with a decrease of the toxicity should represent a potential clinical benefit.

Lung cancer is the leading cause of cancer deaths. Advances in the systemic treatment of non-small cell lung cancer (NSCLC) have increased survival in metastatic EGFR-mutated NSCLC. However resistance to therapy can develop. NSCLC tumors with EGFR-activating mutations are exquisitely sensitive to EGFR tyrosine kinase inhibitors with overall response rates approximating 80%. The third generation EGFR compound osimertinib is a standard first line option. Resistance to the third generation EGFR-TKI osimertinib can develop with a median PFS of 18.9 months. Current research examining acquired resistance to EGFR-TKIs has focused on overcoming these main mechanisms of EGFR-TKI resistance and understanding the impact of co-occurring alterations. Frequently altered pathways concomitantly affected with EGFR in lung cancer are cell cycle genes. This study will explore a strategy to inhibit EGFR and CDK4/6 in resistant EGFR mutated lung cancer patients post progression on osimertinib.

This study will compare the activity of the combination of savolitinib and osimertinib against the combination of savolitinib with placebo to osimertinib in patients with Epidermal Growth Factor Receptor Mutation Positive and MET amplified, locally advanced or metastatic non-small cell lung cancer who have progressed following treatment with osimertinib.

Explore the efficacy and safety of Envafolimab in first line treatment of elderly patients with locally advanced or metastatic non-small cell lung cancer with high PD-L1 expression, view to providing better treatment options for elderly patients with high PD-L1 expression and improving the survival and prognosis of patients .