Adaptive Radiation + Pembrolizumab for Lung Cancer

Overseen By Vanderbilt-Ingram Service for Timely Access

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vanderbilt-Ingram Cancer Center

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Mixed small cell histology, Brain metastases, Uncontrolled illness, Prior malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: Up to 2 years

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new combination of treatments for stage IV or locally advanced lung cancer. It combines adaptive radiation therapy, which adjusts to a patient's cancer response, with immunotherapy drugs like Pembrolizumab (KEYTRUDA) that enhance the immune system's ability to fight cancer, and chemotherapy, which inhibits cancer cell growth. The goal is to determine if these treatments together are safer and more effective than when used separately. Individuals with stage IV lung cancer or locally advanced lung cancer that has spread to nearby tissues might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative combination therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days of enrollment, except for certain corticosteroids, and you must not use any prohibited drugs within 30 days of enrollment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that cemiplimab combined with chemotherapy caused treatment-related side effects in 95.8% of patients, with 43.6% experiencing serious side effects. The FDA has approved cemiplimab with chemotherapy for advanced lung cancer, indicating general safety for this use.

Research has shown that pembrolizumab with pemetrexed and carboplatin has also been studied, with common side effects including tiredness and muscle pain. Adding radiation to this combination did not significantly increase serious side effects.

Studies have found that using nivolumab and ipilimumab together can cause more side effects than nivolumab alone. Despite this, the combination has been safely used in lung cancer patients with radiation.

Similarly, studies show that atezolizumab with radiation did not lead to a significant increase in severe side effects.

These treatments have been tested in various combinations and generally have a reasonable safety profile. However, serious side effects can occur, so discussing potential risks with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine chemotherapy, immune therapy, and radiation in innovative ways to target lung cancer. Unlike standard treatments which often rely on either chemotherapy or radiation alone, these investigational therapies incorporate drugs like pembrolizumab, cemiplimab-rwlc, nivolumab, and ipilimumab. These are immune checkpoint inhibitors that help the immune system better recognize and attack cancer cells. Additionally, the combination of these drugs with radiation therapy might enhance the overall effectiveness, potentially leading to better outcomes by targeting cancer more aggressively. This multi-faceted approach aims to improve both the immediacy and duration of the treatment response compared to traditional methods.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that combining pembrolizumab, carboplatin, and pemetrexed with radiation therapy, as participants in Arm 1 of this trial may receive, holds promise for treating advanced lung cancer. Studies have found that this combination can extend life and slow disease progression in patients with non-small cell lung cancer. Specifically, adding pembrolizumab to chemotherapy has significantly increased survival rates compared to chemotherapy alone. In Arm V of this trial, participants will receive carboplatin and paclitaxel combined with pembrolizumab, which has shown notable survival improvements, especially for patients with certain tumor markers. These findings suggest that using these treatments together with radiation could be more effective than using them separately. ^{6 7 8 9 10}

Who Is on the Research Team?

Evan Osmundson, MD

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with stage IV lung cancer and limited metastases, who can handle the physical demands of the trial (ECOG 0-2). They must have tumor material for PD-L1 testing, managed brain metastases if present, and adequate organ function. Prior immunotherapy is allowed; however, they should not be pregnant or breastfeeding and must use effective contraception.

Inclusion Criteria

Able to submit written informed consent

My organs are healthy enough for treatment, as confirmed by my doctors.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

My lung cancer is of a mixed small cell type.

I have had an organ transplant and take medication to suppress my immune system.

Concurrent enrollment in another clinical trial unless observational or within follow-up period

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive a combination of chemotherapy, immunotherapy, and radiation therapy. Treatment cycles repeat every 3 weeks for up to 4 cycles, followed by maintenance therapy every 21 days for up to 2 years.

Up to 2 years

Every 3 weeks for initial cycles, then every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up visits occur at 4 weeks, 12 weeks, and then every 12 weeks for 2 years.

2 years

4 weeks, 12 weeks, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Nab-paclitaxel
• Pembrolizumab
• Pemetrexed
• Radiation Therapy

Trial Overview The trial tests split-course adaptive radiation therapy combined with pembrolizumab immunotherapy, with or without chemotherapy drugs like carboplatin. The treatment aims to tailor radiation precisely to patient response while enhancing immune system attack on cancer cells.

How Is the Trial Designed?

Group I: Arm XI (nivolumab, ipilumumab, radiation) Experimental Treatment 8 Interventions

Patients receive ipilmumab every 6 weeks and nivolumab every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group II: Arm X (cemiplimab-rwlc, radiation) Experimental Treatment 7 Interventions

Patients receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group III: Arm VIII (pembrolizumab, radiation) Experimental Treatment 7 Interventions

Patients receive pembrolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group IV: Arm VII (carbo, paclitaxel, nivolumab, ipilimumab, radiation) Experimental Treatment 10 Interventions

Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group V: Arm VI (Carboplatin, paclitaxel, cemiplimab-rwlc, radiation) Experimental Treatment 9 Interventions

Patients receive carboplatin, paclitaxel, and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group VI: Arm V (Carboplatin, paclitaxel, pembrolizumab, radiation) Experimental Treatment 9 Interventions

Patients receive carboplatin, paclitaxel, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for 4 up to cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. Patients then receive pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group VII: Arm IX (atezolizumab, radiation) Experimental Treatment 7 Interventions

Patients receive atezolizumab on day 1 of each cycle. Cycles repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group VIII: Arm IV (Carbo, pemetrexed, nivolumab, ipilimumab, radiation) Experimental Treatment 10 Interventions

Patients receive carboplatin, pemetrexed and nivolumab on day 1 of each cycle and ipilimumab on day 1 of every other cycle. Treatment repeats for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then continue to receive ipilmumab and nivolumab on the same schedule for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group IX: Arm III (carboplatin, paclitaxel, cemiplimab-rwlc, radiation) Experimental Treatment 9 Interventions

Patients receive carboplatin, paclitaxel and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group X: Arm II (carboplatin, pemetrexed, cemiplimab, radiation) Experimental Treatment 9 Interventions

Patients receive carboplatin, pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and cemiplimab-rwlc on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Group XI: Arm 1 (carboplatin, pemetrexed, pembrolizumab, radiation) Experimental Treatment 9 Interventions

Patients receive carboplatin, pemetrexed, and pembrolizumab on day 1 of each cycle. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pemetrexed and pembrolizumab on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy on day 1 of each cycle over 5 treatment fractions. All patients also receive fludeoxyglucose F-18 intravenously and fluorine F 18 florilglutamic acid IV and undergo PET/ CT during screening and on study. Patients also undergo collection of blood samples, as well as CT and MRI throughout the trial.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Vanderbilt-Ingram Cancer Center

Lead Sponsor

Trials

221

Recruited

64,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Varian Medical Systems

Industry Sponsor

Trials

63

Recruited

3,700+

Dow R. Wilson

Varian Medical Systems

Chief Executive Officer since 2012

MBA from Dartmouth's Amos Tuck School of Business, BA from Brigham Young University

Dr. Deepak Khuntia

Varian Medical Systems

Chief Medical Officer since 2020

MD from the University of Cambridge, PhD from the University of Leicester

Published Research Related to This Trial

In a trial involving 25 patients with locally advanced non-small-cell lung cancer (LA-NSCLC) and a PD-L1 tumor proportion score of ≥50%, the combination of pembrolizumab and risk-adapted radiotherapy achieved a 1-year progression-free survival rate of 76%, indicating strong efficacy without the use of chemotherapy.

The treatment was well-tolerated, with only 8% of patients experiencing grade 3 adverse events like colitis and esophagitis, and no higher-grade treatment-related adverse events reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial. Ohri, N., Jolly, S., Cooper, BT., et al.[2023]

In a study involving 449 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab showed overall response rates of 15% at 2 mg/kg, 25% at 10 mg/kg every 3 weeks, and 21% at 10 mg/kg every 2 weeks, indicating that the 2 mg/kg dose may be sufficient for efficacy.

The analysis revealed no significant relationship between the dose of pembrolizumab and its efficacy or safety, suggesting that the lower dose of 2 mg/kg every 3 weeks is effective and safe for patients with previously treated advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic evaluation of pembrolizumab dosing in patients with advanced non-small-cell lung cancer. Chatterjee, M., Turner, DC., Felip, E., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

The combination of carboplatin and dose-dense pemetrexed with involved field radiotherapy is feasible for treating locally advanced and oligometastatic non-small cell lung cancer (NSCLC), as shown in a phase I study with 18 enrolled patients.

Despite some dose-limiting toxicities observed, the treatment resulted in a median survival time of 28.6 months, with 13 out of 16 evaluable patients showing a local regional response, indicating promising efficacy for this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma. Shen, X., Denittis, A., Werner-Wasik, M., et al.[2021]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

Pembrolizumab, when combined with carboplatin and pemetrexed, significantly improves overall and progression-free survival rates in patients with non-small cell lung cancer (NSCLC), demonstrating its efficacy as a treatment option.

This case report highlights a unique instance of immune-mediated sarcoidosis developing in a patient with NSCLC after receiving pembrolizumab, indicating potential immune-related side effects of this therapy that require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary Sarcoidosis Activation following Neoadjuvant Pembrolizumab plus Chemotherapy Combination Therapy in a Patient with Non-Small Cell Lung Cancer: A Case Report. Fakhri, G., Akel, R., Salem, Z., et al.[2022]

A 62-year-old patient with advanced non-small-cell lung cancer developed interstitial nephritis after seven cycles of treatment with pembrolizumab, leading to a decline in kidney function and eventual discontinuation of the drug.

Although renal adverse events are rare (reported in less than 3% of patients), this case highlights the importance of monitoring kidney function during pembrolizumab treatment, as early detection of issues like increased serum creatinine levels can aid in management, even if full recovery of kidney function is not guaranteed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial nephritis with pembrolizumab: A case report and review. Peláez Bejarano, A., Montero Pérez, O., Inoriza Rueda, A., et al.[2021]

In a study of 15 patients with inoperable locally advanced non-small cell lung cancer (NSCLC), the combination of paclitaxel, carboplatin, and concurrent radiation therapy resulted in a high overall response rate of 73%, with 13% achieving a complete response and 60% a partial response.

The treatment was associated with manageable toxicity, primarily grade 2 esophagitis in 40% of patients and varying degrees of leukopenia, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A phase I clinical trial of combination chemotherapy of paclitaxel with carboplatin and concurrent radiation therapy in locally advanced non-small cell lung cancer]. Zhu, Y., Zhang, H., Hu, F.[2010]

In the KEYNOTE-407 study involving 1107 patients with untreated metastatic squamous non-small-cell lung cancer, the addition of pembrolizumab to chemotherapy significantly improved overall survival and quality of life without increasing severe toxicity.

Patients receiving pembrolizumab reported better health-related quality of life scores at weeks 9 and 18 compared to those receiving placebo, indicating that pembrolizumab enhances patient well-being while maintaining effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. Mazieres, J., Kowalski, D., Luft, A., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

The maximum tolerated dose (MTD) and recommended dose (RD) of nab-paclitaxel plus carboplatin, combined with thoracic radiotherapy, was determined to be at level 3 (80 mg/m2 of nab-paclitaxel and 2 mg/ml/min of carboplatin), with no significant pulmonary toxicities observed.

The treatment regimen was well tolerated, with 71.4% of patients showing an objective response, indicating its potential efficacy for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small cell lung cancer. Kaira, K., Tomizawa, Y., Imai, H., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10931253/

Exploring the Efficacy of Pembrolizumab in Combination ... Median overall survival (OS) was not reached, with 12- and 18-month OS rates of 75.6% and 61.4%. This chemoimmunotherapy combination ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730424000846

Carboplatin, Weekly Paclitaxel and Pembrolizumab in ... Addition of Pembrolizumab to Carboplatin and weekly Paclitaxel is feasible in elderly patients and substantially improves survival in PD-L1<50%. Attention ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1810865

Pembrolizumab plus Chemotherapy for Squamous Non ... Pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02621398

Study Details | NCT02621398 | Pembrolizumab, Paclitaxel, ... Giving pembrolizumab together with paclitaxel, carboplatin, and radiation therapy may kill more tumor cells. PRIMARY OBJECTIVES: I.

5. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625045080

Low-dose Radiation Therapy Concurrent With ... These findings suggest that upfront LDRT concurrent with atezolizumab plus chemotherapy was effective and tolerable as first-line treatment for ES-SCLC.

7. jto.org jto.org/article/S1556-0864(21)03089-6/fulltext

P63.10 Safety of Simultaneously Performed Radiotherapy ... Atezolizumab was administered to 11 patients. There were no severe adverse events in patients with cranial radiotherapy regardless of simultaneously ...

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(21)02450-9/fulltext

1652P Safety of simultaneously performed radiotherapy in ... The addition of simultaneous radiotherapy to Atezo-based systemic therapy seems not to be associated with increased toxicity in SCLC patients.

9. nrgoncology.org nrgoncology.org/RAPTOR

NRG-LU007: The RAPTOR Study for ES-SCLC Previous studies involving extensive stage SCLC patients have shown that adding radiation therapy to immune therapy is safe and have shown benefit . More ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9509547/

Thoracic RadiothErapy with Atezolizumab in Small cell lUng ... The Phase II DETERRED trial has demonstrated safety of combining atezolizumab with thoracic radiation in NSCLC patients at even higher total ...