Small Cell Lung Carcinoma

The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.

The purpose of this study is to look at how safe 89Zr-DFO-SC16.56 is, and how it is processed by the body in people with small cell lung cancer.

This study is open to adults with small cell lung cancer and other neuroendocrine tumours. The study is in people with advanced cancer for whom previous treatment was not successful or no standard treatment exists. The purpose of this study is to find a suitable dose of BI 764532 (also called obrixtamig) that people with advanced cancer can tolerate. 2 different doses of BI 764532 are tested in this study. Another purpose is to check whether BI 764532 can make tumours shrink. BI 764532 is an antibody-like molecule (DLL3/CD3 bispecific) that may help the immune system fight cancer. The study has 3 parts. In Part 1, participants are put into 2 groups randomly, which means by chance. Participants have an equal chance of being in either group. One group gets dose 1 of BI 764532 and the other group gets dose 2 of BI 764532. In Part 2 and Part 3, all participants receive the same dose of BI 764532. Part 2 and Part 3 are open to people with a certain kind of tumour called extrapulmonary neuroendocrine carcinoma. All participants receive BI 764532 as an infusion into a vein when starting treatment. If there is benefit for the participants and if they can tolerate it, the treatment is given up to the maximum duration of the study. During this time, participants visit the study site regularly. The total number of visits depends on how they respond to and tolerate the treatment. The first study visits include an overnight stay to monitor participants´ safety. Doctors record any unwanted effects and regularly check the general health of the participants.

The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.

Lung cancer is a highly prevalent disease worldwide in women and men. In 2022, lung cancer stood as the most frequently diagnosed cancer with approximately 2.48 million new cases on a global scale, followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer is the leading cause of cancer death worldwide according to data provided by the International Agency for Research on Cancer. In 2022 they estimated a 1.8 million deaths across the world. Specifically in Spain, from 1980 to 2022, lung cancer led to 745,182 deaths. Histologically, lung cancer (LC) can be classified into two major subtypes: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), accounting for 85% and 15% of LC patients, respectively. Smoking is the major risk factor for SCLC. There are two stages of SCLC: limited-stage SCLC (LS-SCLC) and extensive-stage SCLC (ES-SCLC). Limited-stage (LS) means that the cancer is located on the ipsilateral hemithorax that can be encompassed within a radiation port while extensive-stage (ES) means that the cancer has spread widely throughout the lungs, to non-regional lymph nodes or to other organs. At present, LS is identified in \~30% of patients, and ES is identified in \~70% of patients with SCLC. With a 5-year survival rate of less than 7%, SCLC is still one of the most lethal malignancies and it is also characterized by early metastatic spread. Reflecting this high metastatic capacity, two thirds of patients already have tumor cell dissemination outside the chest at the time of initial diagnosis (ES-SCLC). Therefore, the number of patients with LS-SCLC who can benefit from multimodality therapy with potentially curative intent is limited. SCLC is a highly aggressive form of LC that typically recurs and progresses rapidly despite initial response to chemotherapy and radiotherapy in patients with LS-SCLC. The etoposide/platinum (EP) combination was the standard of care (SoC) for patients with ES-SCLC until 2019, when the addition of immunotherapy to EP chemotherapy was shown to improve survival, with up to 17% of patients remaining alive at 3 years. On the other hand, the SoC for patients with LS-SCLC is concurrent platinum-based chemoradiotherapy (cCRT) ± prophylactic cranial irradiation (PCI) that remained unchanged for decades. Several studies have shown that concurrent chemoradiotherapy (cCRT) is more effective than sequential CRT (sCRT) in LS-SCLC. Nonetheless, subject to the lymph node regions involvement and treatment-related toxicities, some patients do not undergo concurrent CRT and instead receive sequential CRT. In a non-interventional, retrospective cohort study of limited-stage SCLC patients conducted in France, Italy and the UK, sequential chemoradiotherapy accounts for 37.6% of all treatment patterns while concurrent chemoradiotherapy accounts for 35.1% of the whole therapies used as first line. ADRIATIC (NCT03703297) is a phase 3, randomized, double-blind, placebo-controlled, multicenter, global study evaluating durvalumab ± tremelimumab as consolidation therapy for patients with LS-SCLC who have not progressed after cCRT. Positive high-level results of the ADRIATIC clinical trial showed durvalumab demonstrated a statistically significant and clinically meaningful improvement in the dual primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients with LS-SCLC who had not progressed following cCRT compared to placebo. Durvalumab was well tolerated, and AEs were consistent with the known safety profile. These data support the consolidation of durvalumab as a new SoC for patients with LS-SCLC who have not progressed after cCRT. There is limited information on the effectiveness and safety of durvalumab in a broader patient population with LS-SCLC, including those who received sequential CRT. Therefore, there remains an unmet need for additional data to help support and inform the healthcare decisions on the use of durvalumab as consolidation treatment for patients with LS-SCLC in real-world clinical practice. In addition, ADRIATIC study did not allow to include patients with ECOG PS 2 assessed after CRT. The present phase IIIb study will assess the safety and effectiveness of durvalumab in real world like LS-SCLC population. Furthermore, this trial will focus on patient characteristics, treatment exposure, administration, quality of life (QoL), effectiveness and safety providing insights into durvalumab use.

The purpose of this study is to find out whether a Hospital-at-Home (HaH) program is a more efficient way to monitor people's health after receiving tarlatamab than monitoring in the hospital (inpatient).

The purpose of the study is to see if stereotactic radiosurgery/SRS is an effective treatment for people with a new diagnosis of brain metastases from small cell lung cancer/SCLC.

This is a Phase 2 study of GV20-0251 in combination with anti-PD-1 monoclonal antibodies (including tislelizumab and toripalimab) for the treatment of participants with unresectable, locally advanced, or metastatic solid tumors who are refractory to, intolerant of, or ineligible for standard of care.

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[225Ac\]Ac-ETN029 and the safety and imaging properties of \[111In\]In-ETN029 in patients aged ≥ 18 years with locally advanced or metastatic DLL3 positive cancers.

This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat. Participants in this study must have cancer that has come back or did not get better with treatment. Participants must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called PF-08046050. PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells. This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body. This study has 5 different study parts. Part A and Part B of the study will find out how much PF-08046050 should be given to participants. Part C will use the information from Parts A and B to see if PF-08046050 is safe and if it works to treat certain solid tumor cancers. Part D and E of the study, together with information from Parts A and B, will find out how much PF-08046050 should be given in combination with other anti-cancer agents. Part E will use the information from Parts A, B, and D to see if PF-08046050 is safe in combination with other anti-cancer agents and if it works to treat a certain solid tumor.

The goal of the Dose Escalation phase of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion (RDE) of NKT3964 in adults with advanced or metastatic solid tumors. The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDE based on objective response rate (ORR) and determine the preliminary recommended Phase 2 dose (RP2D).

This is a single-center, prospective, single-arm interventional study with historical control, designed to evaluate the clinical value of a multidisciplinary team (MDT)-based decision-making umbrella decision model in elderly patients with lung cancer. A total of 2,000 patients aged 60-90 years with newly diagnosed non-small cell or small cell lung cancer will be enrolled. Each patient will undergo comprehensive geriatric assessment and receive an individualized treatment plan formulated by an MDT comprising thoracic surgeons, geriatricians, oncologists, pulmonologists, rehabilitation therapists, and radiologists. Treatment options include surgery, ablation, stereotactic body radiotherapy (SBRT), neoadjuvant immunochemotherapy, targeted therapy, and best supportive care. The primary outcome is 3-year progression-free survival (PFS). Secondary outcomes include overall survival, objective response rate, quality of life (EORTC QLQ-LC43), incidence of adverse events (CTCAE v5.0), and healthcare economics. Historical controls (2014-2024) will be extracted from hospital records and matched using propensity score matching. The study aims to establish a standardized MDT pathway to improve treatment outcomes and reduce risks in the geriatric lung cancer population.

This is a phase III clinical trial that aims to evaluate whether increasing the dose of radiotherapy given twice a day can improve treatment outcomes in patients with localized small cell lung cancer (SCLC). All patients will receive standard chemotherapy with cisplatin and etoposide and will be randomly assigned to one of three radiotherapy regimens. The main objective is to determine whether this intensified radiotherapy improves progression-free survival and overall survival. The study will also compare two different dose escalation strategies and assess treatment side effects and patients' quality of life. This research may help identify a more effective treatment approach for patients with limited-stage SCLC and could contribute to improving long-term survival in this aggressive type of cancer

This is a phase 1, single-center, open-label study that enrolls adult subjects with extensive stage lung cancer or stage IV non-small cell lung cancer that is platinum-refractory and received PD-1 and/or PD-L1 therapy. The purpose of this study is to test the safety of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the GD2 antigen (iC9-GD2.CAR.IL-15 T cells) in subjects with lung cancer. How much (dose) of the iC9-GD2.CAR.IL-15 T cells are safe to use without causing too many side effects and what is the maximum dose that could be tolerated will be studied. Modified immune cells as an experimental treatment that combines antibodies and T cells will be used. Antibodies are proteins that protect the body from foreign invaders like bacteria. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill viruses and other cells, including tumor cells. Although antibodies and T cells have been used to treat cancer and they both have shown promise, neither alone has been able to cure most patients. This study will combine T cells and antibodies to create a more effective treatment. The treatment that is being researched in this study is called autologous T lymphocyte chimeric antigen receptor cells targeted against the disialoganglioside (GD2) antigen that expresses Interleukin (IL)-15, and the inducible caspase 9 safety switch (iC9). The short name for this treatment is iC9.GD2.CAR.IL-15 T cells therapy is an experimental therapy and has not been approved by the Food and Drug Administration. There are two steps. In the first step, blood will be collected from the subjects to prepare the iC9-GD2.CAR.IL-15 T cells. T cells will be isolated from the blood and modified to make iC9-GD2.CAR.IL-15. In the second step, the iC9-GD2.CAR.IL-15 T cells produced from the subject's own blood will be administered to the subject.

This study plans to enroll limited-stage small cell lung cancer (LS-SCLC) patients who have achieved disease control after concurrent chemoradiotherapy (cCRT). Tissue samples collected at initial diagnosis and serial peripheral blood samples obtained at multiple post-cCRT timepoints will be analyzed using targeted next-generation sequencing to investigate the correlation between molecular residual disease (MRD) status and tumor recurrence/metastasis. For patients with MRD-positive results, a therapeutic strategy combining immunotherapy with anti-angiogenic agents will be implemented with the aim of improving clinical outcomes.

In clinical trials, patients are selected according to strict eligibility criteria (inclusion and exclusion criteria). These criteria aim to ensure homogeneity within the trial population, but may omit patients with specific characteristics, comorbidities or co-medications. Indeed, patients of advanced age, with comorbidities or brain metastases, who are frequently encountered in clinical practice, are often excluded from clinical trials. Real-life data in oncology play a vital role in assessing the efficacy of therapies and therapeutic strategies, complementing data from controlled clinical trials. They make it possible to analyze a larger population and take into account multiple variables such as patient history, co-medications and comorbidities, but also to analyze efficacy and toxicity data in populations not represented in clinical trials. The establishment of a prospective cohort including various stages and histologies will make it possible to set up a platform of available data, including a maximum of data linked to the patient, his tumor and his treatments, collected longitudinally until the patient's death (or the end of the study). In parallel with this cohort, the project aims to set up a longitudinal plasmatheque (from diagnosis to death, or at the end of the study), as well as a tumorotheque (samples systematically stored as part of care by the CHU tumorotheque, and for which patient consent allows their use in research depending on the material available) for patients with available tumor samples. This will enable the construction of ancillary projects to validate research hypotheses, for example concerning the identification of mechanisms of resistance to therapies.

Although small cell lung cancer (SCLC) responds dramatically to initial platinum-based chemotherapy, recurrences are nearly universal. The addition of atezolizumab, an immune checkpoint inhibitor, to front-line chemotherapy has recently demonstrated an improvement in overall survival (OS) in extensive stage SCLC (ES-SCLC). Subsequent lines of therapies are associated with modest efficacy in patients with relapsed disease, and the median overall survival is still 12 to 13 months at best. Cirtuvivint is a small molecule inhibitor of the CDC2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs); inhibiting CLKs and DYRKs has been shown in preclinical models to cause tumor growth inhibition and sensitize cancer cells to cytotoxic chemotherapy. This study is testing the hypothesis that adding cirtuvivint to chemotherapy in patients with relapsed SCLC will be well tolerated and improve the response rate and progression-free survival (PFS).

This phase II clinical trial will study the safety and efficacy of onvansertib to treat patients with small cell lung cancer (SCLC) who have either not responded to or are unable to tolerate chemotherapy. Onvansertib is a drug that inhibits polo-like kinase 1 (PLK-1), an enzyme that is over-expressed in many cancer cells and is involved in cellular repair.

The purpose of this research study is to learn more about lung cancer (NSCLC or SCLC) diagnosed in adults at ages 45 or younger.

The purpose of this study is to evaluate the efficacy of radiotherapy as part of the combined treatment approach for patients diagnosed with histopathologically confirmed small cell lung cancer (SCLC) in the advanced stage of extensive disease (ED) who are undergoing chemo-immunotherapy. The planned study aims to assess the impact of incorporating consolidative radiotherapy into the treatment strategy, focusing on residual changes following chemo-immunotherapy (during immunotherapy) and its effect on progression-free survival. This research experiment will be conducted as a randomized multi-center study, comprising the following treatment arms: * Arm I: Continuation of standard of care - PDL1/PD1 immunotherapy (durvalumab or atezolozumab) after chemo-immunotherapy based on platinum compounds; * Arm II: Standard of care, followed by consolidating radiotherapy of the chest area and possibly metastases (if indicated) in doses and for palliative indications (total dose of 30 Gy in 10 daily doses of 3 Gy each); * Arm III: Standard of care, followed by consolidating radiotherapy in the radical/ablative doses (total dose of 45 Gy delivered in 15 daily fractions of 3 Gy for the chest area, and total dose of 24 Gy in single fractions of 8 Gy administered every 2-3 days for the metastatic lesions) of the chest area and all metastatic lesions. Additionally, as part of routine weekly blood collections, an extra volume of 10 ml of blood will be collected. This additional blood sample will be obtained before starting radiotherapy, during each week of radiotherapy (maximum three collections), and at the time of disease progression (one collection), resulting in a total of five extra samples. The collected blood will be prepared, stored and used for circulating tumor DNA (ctDNA) testing, according to the protocol. The ctDNA analysis data will be utilized as a potential marker to determine the time to progression and assess the benefits derived from the administered radiotherapy.

Small cell lung cancer (SCLC) is an aggressive disease that is characterized by rapid growth and the early development of metastases. Patients typically respond to initial chemotherapy but quickly experience relapse, resulting in a poor long-term outcome. Therapeutic innovations that substantially improve survival have historically been limited, and reliable, predictive biomarkers are lacking. Ongoing research has advanced the understanding of molecular categories and the immunologic microenvironment of SCLC, which in turn has helped improve disease classification and staging. Considering the role of molecular alterations has not yet fully to be defined in the treatment of SCLC, there is an urgent recognition that molecular alterations in the SCLC are important to predict response and survival for novel therapies and ongoing clinical trials. Advances in research have revealed critical information regarding biologic characteristics of the disease, which may lead to the identification of vulnerabilities and the development of new therapies. Further research focused on identifying biomarkers and evaluating innovative therapies will be paramount to improving treatment outcomes for patients with SCLC. In summary, identification of (genetic) biomarkers in SCLC is increasingly essential to perform molecular diagnostics and individualized treatments. This project aims to create a registry of patients with SCCL to further the characterization of molecular alterations and develop (novel) treatments based on the detection.

There is a prospective risk-adapted evaluation of the optimal dose of radiotherapy for definitive radiotherapy of locally advanced small cell lung cancer within the corridor recommended as standard therapy according to the current interdisciplinary S3 guideline of the German Cancer Society/Cancer Aid/AWMF

This is a multicenter, randomized, double-blind, placebo-controlled, phase III study to evaluate the efficacy and safety of AL8326 tablets in small cell lung cancer (SCLC) patients with disease progression or recurrence after receiving at least second-line treatment regimens.

Patients with extensive-stage small-cell lung cancer (ES-SCLC) have poor prognosis, with limited treatment options. Chemo-immunotherapy is the standard 1st-line therapy for patients with ES-SCLC.When 4 cycles of etoposide+carboplatin (EC) or etoposide+cisplatin(EP) chemotherapy combined with PD-L1 inhibitor are effective, guidelines recommend additional thoracic radiotherapy. In this study, the investigators bring radiotherapy forward, which means that after 2 cycles of EC chemotherapy plus Adebrelimab, participants with response（PR/CR/SD）will receive concurrent radiotherapy and 2 cycles of EC chemotherapy plus Adebrelimab, then maintenance therapy with Adebrelimab （Q3W）. The purpose of this study is to explore the safety and efficacy of Adebrelimab combined with concurrent chemoradiotherapy in untreated participants with extensive-stage small cell lung cancer.

This is an open-label, single arm Phase II study designed to evaluate the efficacy and safety of adebelizumab combined with carboplatin/Cisplatin plus (+) etoposide and concurrent radiotherapy in the first-line treatment of patients with extensive stage oligometastatic small cell lung cancer.