Clinical Research Directory

A Study of SGN-CEACAM5C in Adults With Advanced Solid Tumors

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.

MDT-Based Umbrella Decision Model for Geriatric Lung Cancer Patients

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.

Dose-Escalation Radiotherapy in Limited-Stage Small Cell Lung Cancer: A Phase III Randomized Trial

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

A Study of Hospital-at-Home for People Receiving Tarlatamab

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).

Durvalumab After Chemoradiotherapy in Limited Stage Small Cell Lung Cancer.

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.

Phase I Study of [225Ac]Ac-ETN029 in Patients With Advanced DLL3-expressing Solid Tumors

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.

Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98)

This study is a rolling arm study of investigational agents as monotherapy or in combination with pembrolizumab in participants with anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) refractory ES-SCLC in need of second-line treatment. This study will have 2 parts: an initial safety lead-in to determine safety and tolerability for experimental combinations of investigational agents without an established recommended phase 2 dose (RP2D) followed by an efficacy evaluation. Investigational agents will initiate directly in or be added to the efficacy evaluation after an initial evaluation of safety and tolerability of the investigational agent has been completed in a separate study or in the safety lead-in of this study. If an RP2D for a combination being evaluated in the safety lead-in is established from another study, then the efficacy evaluation may begin at the determined RP2D. There will be no hypothesis testing in this study.

The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)

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.

A Study of LY4175408 in Participants With Advanced Cancer

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.

A French Real-life Study: EvaluatioN of durvALumab Utilization and Effectiveness for First Line Extensive Stage Small Cell Lung Cancer.

Small cell lung cancer (SCLC), characterized by rapid proliferation, high growth fraction and early development of metastases, is the most aggressive form of lung cancer. In 2021, an estimated 2.3 million people around the world are diagnosed with lung cancer. In France, in 2018, with 46 363 new cases and 33 117 deaths, lung cancer represented the second most common cancer and the first cause of death from cancer. Among those, SCLC represented 10,8% of all new lung diagnosis, and about two thirds presented at the extensive stage (ES-SCLC). Since last three decades, standard treatment in ES-SCLC is based on combination chemotherapy with a platinum agent and etoposide in first-line with or without concurrent radiation therapy. Then, the second-line of treatment is topotecan, with few results in terms of response rates and survival rate. However, the emergence of immune checkpoint inhibitors targeting the programmed cell death receptor-1 (PD-1)/PD-ligand 1 (PD-L1) pathway, having an important role in immune regulation became an alternative method in the management and care of disease. Indeed, recent studies have shown an overall survival (OS) benefit for patients with ES-SCLC treated in first line with a combination of platinum-etoposide and immune checkpoint inhibitors. Atezolizumab (Tecentriq®, Roche) and durvalumab (Imfinzi®, AstraZeneca), two anti-Programmed death-ligand 1 (PD-L1) antibodies, delivered positive phase III results, respectively through the Impower-133 and CASPIAN studies, and were granted European market authorisations. Durvalumab is approved for use in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of patients with ES-SCLC. On March 10, 2020 French health authorities allowed durvalumab utilization in this setting through a national "early access program" (Autorisation Temporaire d'Utilisation "de cohorte" - ATUc), thus preceding the European market authorization (August 28, 2020). Since 2020 October 1st, durvalumab is used as a post ATU treatment. Since 2020, French AURA treatment guidelines for SCLC have referenced durvalumab in combination with chemotherapy as a first-line treatment option for patients with ES-SCLC. Whereas the safety and efficacy of the durvalumab have been evaluated in a clinical trial, data are required to further evaluate the use of durvalumab in real-life condition and in less selected population than in clinical trials.

Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer

The purpose of this multicenter study in China is to evaluate the safety and efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with untreated extensive-stage small cell lung cancer.

A Study of Stereotactic Radiosurgery (SRS) for People With Lung Cancer That Has Spread to the Brain

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.

A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors

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).

DAREON™-5: A Study to Test Whether Different Doses of BI 764532 Help People With Small Cell Lung Cancer or Other Neuroendocrine Cancers

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 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 2 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, all participants receive the same dose of BI 764532. Part 2 is 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.

Autologous CAR T-Cells Targeting the GD2 Antigen for Lung 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.

ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers

In this study, patients with small cell or non-small cell lung cancer will receive ADI-PEG 20, gemcitabine, and docetaxel after demonstrated progression on frontline therapy. In phase I of the study, up to 6 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at that dose level to assess efficacy. Although safety and tolerability has been previously determined in the sarcoma population, dose de-escalations of the chemotherapies in that patient population were required. Therefore, a phase I portion will be incorporated to determine the RP2D of the triplet in this population.

Exploration of Treatment Strategies After Concurrent Chemoradiotherapy for LS-SCLC Guided by MRD

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.

Prospective, Longitudinal Biocollection in Thoracic Oncology, Including Newly Diagnosed Lung Cancer Patients

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.

PET/CT Imaging of Small Cell Lung Cancer Using 89Zr-DFO-SC16.56

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.

Small Cell Lung Cancer Irinotecan and CDC2-like Kinase Inhibition Trial (SLICK Trial)

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).

Study of PLK1 Inhibitor, Onvansertib, in Relapsed Small Cell Lung Cancer

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.

Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)

A study to assess the safety, tolerability, and PK of tarlatamab in participants with SCLC

Biology of Young Lung Cancer Study: The YOUNG LUNG Study

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

Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-158/KEYNOTE-158)

In this study, participants with multiple types of advanced (unresectable and/or metastatic) solid tumors who have progressed on standard of care therapy will be treated with pembrolizumab (MK-3475).