Targeted Radiation + Drug Therapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
+8 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to see whether adding liver stereotactic ablative radiotherapy/L-SABR to standard drug therapy is better than standard drug therapy alone for people with metastatic non-small cell lung cancer/NSCLC.
What data supports the effectiveness of the drug therapy for lung cancer?
Research shows that combining PD-L1 inhibitors with chemotherapy is more effective for advanced non-small cell lung cancer (NSCLC) than using PD-L1 inhibitors alone. Additionally, combining PD-1 inhibitors with chemoradiotherapy improves survival rates for stage III NSCLC.
3691214Is the combination of targeted radiation and drug therapy for lung cancer safe?
The combination of PD-1/PD-L1 inhibitors with chemotherapy has been studied for lung cancer, showing that while it can improve outcomes, it also comes with potential side effects that need careful management. Common side effects include immune-related reactions and other adverse events, but these can often be managed effectively with proper medical guidance.
1781113How is the treatment of targeted radiation combined with drug therapy for lung cancer different from other treatments?
This treatment is unique because it combines targeted radiation with immunotherapy drugs that block PD-1/PD-L1, enhancing the body's immune response against cancer cells. This combination has shown to be more effective than using either treatment alone, as radiation can increase the expression of PD-L1 on tumor cells, making them more susceptible to the immunotherapy.
245610Do I need to stop my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have active autoimmune disease, you may not be eligible to participate.
Eligibility Criteria
This trial is for adults over 18 with stage IV NSCLC without certain genetic mutations, who have liver metastases and are starting standard immunotherapy +/- chemotherapy. They must have a decent performance status and normal liver function tests. People with active hepatitis, prior liver radiation, pregnancy/breastfeeding, ineffective contraception use or significant immunosuppression can't join.Inclusion Criteria
I am over 18 years old.
I am starting standard immunotherapy with or without chemotherapy soon.
I have newly diagnosed lung cancer that has spread to my liver.
My stage IV lung cancer does not have specific genetic changes.
I am a candidate for targeted radiation therapy on liver cancer spots.
I can take care of myself and am up and about more than half of my waking hours.
I am starting or planning to start standard care with anti-PD(L)-1 therapy alone or with chemotherapy.
Exclusion Criteria
I am on long-term steroids or drugs for immune conditions.
I am not using any form of birth control.
I have active Hepatitis B or C.
I have had radiation therapy targeted at my liver before.
Participant Groups
The study is testing if adding targeted radiation therapy (L-SABR) to the usual drug treatments (anti-PD-(L)1 based immunotherapy and platinum-based chemotherapy) provides better outcomes for patients with metastatic NSCLC that has spread to the liver.
2Treatment groups
Experimental Treatment
Active Control
Group I: L-SABR ArmExperimental Treatment3 Interventions
Participants randomized to the experimental arm will continue with standard of care treatment but will also undergo radiation simulation for L-SABR/Liver Stereotactic Ablative Radiation Therapy.
Group II: Control ArmActive Control2 Interventions
Participants randomized to the control arm will be treated according to the standard of care.
Anti-PD-(L)1 based immunotherapy is already approved in United States, United States, United States, United States, United States, European Union, European Union, European Union, European Union, European Union, China, China for the following indications:
๐บ๐ธ Approved in United States as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
- Cervical cancer
- Endometrial carcinoma
๐บ๐ธ Approved in United States as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
๐บ๐ธ Approved in United States as Atezolizumab (Tecentriq) for:
- Urothelial carcinoma
- Non-small cell lung cancer
- Triple-negative breast cancer
- Hepatocellular carcinoma
๐บ๐ธ Approved in United States as Avelumab (Bavencio) for:
- Merkel cell carcinoma
- Urothelial carcinoma
- Renal cell carcinoma
๐บ๐ธ Approved in United States as Durvalumab (Imfinzi) for:
- Urothelial carcinoma
- Non-small cell lung cancer
- Biliary tract cancer
๐ช๐บ Approved in European Union as Pembrolizumab (Keytruda) for:
- Melanoma
- Non-small cell lung cancer
- Head and neck squamous cell carcinoma
- Urothelial carcinoma
- Colorectal cancer
- Hepatocellular carcinoma
- Renal cell carcinoma
๐ช๐บ Approved in European Union as Nivolumab (Opdivo) for:
- Melanoma
- Non-small cell lung cancer
- Renal cell carcinoma
- Hodgkin lymphoma
- Squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer
๐ช๐บ Approved in European Union as Atezolizumab (Tecentriq) for:
- Urothelial carcinoma
- Non-small cell lung cancer
- Triple-negative breast cancer
๐ช๐บ Approved in European Union as Avelumab (Bavencio) for:
- Merkel cell carcinoma
- Urothelial carcinoma
- Renal cell carcinoma
๐ช๐บ Approved in European Union as Durvalumab (Imfinzi) for:
- Urothelial carcinoma
- Non-small cell lung cancer
๐จ๐ณ Approved in China as Camrelizumab (SHR-1210) for:
- Hodgkin lymphoma
- Non-small cell lung cancer
๐จ๐ณ Approved in China as Sintilimab (IBI308) for:
- Non-small cell lung cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Memorial Sloan Kettering Westchester (All Protocol Activities)Harrison, NY
Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)Commack, NY
Memorial Sloan Kettering Monmouth (All Protocol Activities)Middletown, NJ
Memorial Sloan Kettering Nassau (All protocol activities)Rockville Centre, NY
More Trial Locations
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Who is running the clinical trial?
Memorial Sloan Kettering Cancer CenterLead Sponsor
References
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.
Clinical Trials Integrating Immunotherapy and Radiation for Non-Small-Cell Lung Cancer. [2016]Methods of harnessing the immune system to treat cancer have been investigated for decades, but yielded little clinical progress. However, in recent years, novel drugs that allow immune recognition and destruction of tumor cells are emerging as potent cancer therapies. Building upon previous immunotherapy strategies that included therapeutic vaccines, recombinant cytokines, and other immunostimulatory agents, newer immunotherapy agents targeting immune checkpoints including programmed cell death 1, programmed cell death ligand-1, and cytotoxic T-lymphocyte-associated protein 4, among others, have garnered substantial enthusiasm after demonstrating clinical activity in a broad spectrum of tumor types. Trials evaluating immune checkpoint inhibitors in metastatic non-small-cell lung cancer (NSCLC) demonstrate robust and durable responses in a subset of patients. However, with overall response rates less than 20%, combinatorial strategies that extend the benefit of these agents to more patients are desirable. The integration of radiotherapy with immunotherapy is a conceptually promising strategy, as radiotherapy has potent immunomodulatory effects and may contribute not only to local control but may also augment systemic antitumor immune response. Preclinical data and case reports suggest the potential for robust clinical responses in metastatic NSCLC patients using this strategy, but prospective clinical trials evaluating the integration of radiation and immunotherapy are limited. The use of immunotherapy in nonmetastatic settings is also intriguing but understudied. We review the potential clinical settings of interest for the partnering of immunotherapy and radiation in NSCLC, including early stage, locally advanced, and metastatic disease, and review completed, accruing, and developing clinical trials.
Radiation Therapy Plus Anti-Programmed Death Ligand 1 Immunotherapy: A Review on Overall Survival. [2019]To analyze current preclinical trials and early clinical trials on the effects of concomitant anti-programmed death ligand 1 (anti-PD-L1) immunotherapy and radiation therapy on progression-free survival (PFS) and overall survival (OS) for advanced melanoma and metastatic non-small cell lung cancer (NSCLC) patients.
Combination Therapy of Radiotherapy and Anti-PD-1/PD-L1 Treatment in Non-Small-cell Lung Cancer: A Mini-review. [2019]Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. In the clinical setting, patients receiving radiotherapy before anti-PD-1 treatment have had a significantly better prognosis than those who have not undergone radiotherapy. In the present report, we reviewed previous studies of the combination of radiotherapy and anti-PD-1/PD-L1 treatment for NSCLC. In addition, we report our case of a patient whose PD-L1 expression gradually increased in brain metastases from NSCLC after repeated radiotherapy. In the perspectives portion, we focused on the questions of how to integrate radiotherapy into anti-PD-1/PD-L1 agent regimens and described several ongoing clinical trials.
Radiation therapy and PD-1/PD-L1 blockade: the clinical development of an evolving anticancer combination. [2023]Several inhibitors of programmed cell death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved as a form of immunotherapy for multiple cancers. Ionizing radiation therapy (RT) has been shown to enhance the priming and effector phases of the antitumor T-cell response rendering it an attractive therapy to combine with PD-1/PD-L1 inhibitors. Preclinical data support the rational combination of the 2 modalities and has paved way for the clinical development of the combination across a spectrum of cancers. In this review, we highlight the preclinical and clinical development of combined RT and PD-1/PD-L1 blockade to date. In addition to a comprehensive evaluation of available safety and efficacy data, we discuss important points of consideration in clinical trial design for this promising combination.
Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial. [2021]Consolidative programmed death ligand-1 (PD-L) inhibition after chemoradiotherapy improves overall survival and progression-free survival (PFS) for stage III non-small cell lung cancer (NSCLC) and requires safety evaluation for incorporation of programmed cell death 1 (PD-1) inhibition at the onset of chemoradiotherapy.
Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer. [2020]The combination of an anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) monoclonal antibody with platinum-based chemotherapy can improve outcomes for patients with advanced non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) compared with chemotherapy alone. For patients receiving these new treatment regimens, it is important that toxicities be managed effectively. A particular challenge can be determining the etiology of an event, especially when there are overlapping symptoms that can be attributed to either immunotherapy or to platinum-based chemotherapy. Here, we evaluate adverse events (AEs) reported in clinical trials of combination therapy with an anti-PD-1 or anti-PD-L1 (anti-PD-[L]1) immunotherapy and chemotherapy to provide information on toxicity management.
Adverse Effects of Anti-PD-1/PD-L1 Therapy in Non-small Cell Lung Cancer. [2020]Currently, immunotherapy has shown great efficacy in clinical trials, and monoclonal antibodies directed against immune checkpoint PD-1/PD-L1 have shown encouraging results in first-line or second-line treatment of non-small cell lung cancer patients. Meanwhile, anti-PD-1/PD-L1 immune checkpoint drugs combined with other treatments, such as chemotherapy, targeted therapy as well as anti-CTLA-4 checkpoint therapy, are considered an attractive treatment with higher efficacy. However, toxicity associated with PD-1/PD-L1 blockade is worth attention. Understanding the adverse effects caused by anti-PD-1/PD-L1 immunosuppressive agents is vital to guide the clinical rational use of drug. In this review, we summarized the adverse effects that occurred during the clinical use of anti-PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer and discussed how to effectively manage and respond to these adverse reactions.
Immune-related adverse events of a PD-L1 inhibitor plus chemotherapy versus a PD-L1 inhibitor alone in first-line treatment for advanced non-small cell lung cancer: A meta-analysis of randomized control trials. [2021]The addition of chemotherapy to a programmed death 1/programmed death ligand 1 (PD-L1) inhibitor is a more effective option as a first-line treatment for advanced non-small cell lung cancer (NSCLC). It might also inhibit an overactive immune response and thereby reduce immune-related adverse events (irAEs). This meta-analysis assessed the rate of irAEs with a PD-(L)1 inhibitor plus chemotherapy (I+C) versus a PD-(L)1 inhibitor alone (I) and evaluated the indirect relative risk (RR) of I+C versus I.
PD-1 restrains IL-17A production from ฮณฮด T cells to modulate acute radiation-induced lung injury. [2022]Combining radiotherapy (RT) with programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has been shown to enhance anti-tumor effects in the treatment of non-small cell lung carcinoma (NSCLC). Pulmonary toxicity is a major adverse effect of thoracic RT in NSCLC patients, whether it is administered alone or in combination with PD-1/PD-L1 inhibitors. This study aimed to evaluate the potential pulmonary toxicity of RT combined with concurrent PD-1 inhibitor and to clarify the underlying mechanisms.
The safety of first and subsequent lines of PD-1/PD-L1 inhibitors monotherapy in non-small cell lung cancer patients: a meta-analysis. [2022]In both first or subsequent therapy of patients with non-small cell lung cancer (NSCLC), some programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors have shown prominent efficacy and safety. However, the disease spectra of side effects in different therapy time might exist heterogeneity. In this meta-analysis, we assessed and compared the safety of PD-1/PD-L1 inhibitors in first or subsequent line therapy. And the system-specific disease spectra of both treatment-related adverse events (trAEs) and immune-related adverse events (irAEs) were summarized.
Real-world utilization of PD-1/PD-L1 inhibitors with palliative radiotherapy in patients with metastatic non-small cell lung cancer. [2022]Programmed cell death protein 1 (PD-1) blockade plus radiotherapy may be a promising strategy to improve the prognosis of patients with metastatic non-small cell lung cancer (NSCLC). However, the optimum combined scheme, treatment time of radiotherapy, and irradiated lesion have not been fully determined.
Tislelizumab-related enteritis successfully treated with adalimumab: A case report. [2022]With programmed death-1 (PD-1) inhibitors becoming the standard treatment for lung cancer, PD-1-related adverse reactions and treatment have gradually become prominent.
Interleukin 8 in plasma is an efficacy marker for advanced non-small cell lung cancer treated with hypofractionated radiotherapy and PD-1 blockade. [2023]Programmed death-1 (PD-1) blockade promotes combination therapy in advanced non-small cell lung cancer (NSCLC), hypofractionated radiotherapy (HFRT) and chemotherapy combined with immunotherapy improves the outcome of prognosis in advanced NSCLC, while effective biomarkers to follow prognostic efficacy are still to be found.