Immunotherapy + Radiation for Lung Cancer

Overseen By Hector Gonzalez, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Targeted therapies, Immunosuppressives

Disqualifiers: Autoimmune disorders, Untreated brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized Phase II study which is designed to determine the impact of stereotactic radiotherapy and durvalumab on quality-of-life and oncologic outcomes in patients with advanced non-small cell lung cancer. Durvalumab (Imfinzi) and stereotactic radiotherapy, with each fraction of radiotherapy is given every other day on a standard stereotactic ablative radiotherapy (SAbR) schedule or every four weeks on the personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) schedule. Subjects will be followed for a period of 2 years after completion of treatment or until death, whichever occurs first. Specifically, subjects will be followed at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months following treatment. After the 2 year follow up, the patient can continue routine follow up with their physicians, per standard of care. Subjects removed from therapy for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot take certain cancer treatments, investigational drugs, or immunosuppressive medications during the trial. It's best to discuss your specific medications with the study team.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but certain medications are not allowed during the study. You cannot take other cancer treatments, investigational drugs, or immunosuppressive medications above a certain dose. It's best to discuss your current medications with the study team to see if they are allowed.

What data supports the idea that Immunotherapy + Radiation for Lung Cancer is an effective treatment?

The available research shows that using the drug durvalumab after radiation therapy significantly improves survival in patients with advanced lung cancer. One study highlights that this combination is now a standard treatment because it has shown a significant improvement in survival rates for patients who cannot have surgery. Another study suggests that patients who receive durvalumab after radiation therapy live longer without the cancer spreading compared to those who only receive radiation. This combination is especially beneficial for patients who cannot undergo chemotherapy due to other health issues, as it provides better survival outcomes than radiation alone. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Durvalumab and Stereotactic Radiation Therapy for lung cancer?

Research shows that using Durvalumab after chemoradiotherapy significantly improves survival in patients with non-small cell lung cancer. This combination is now a standard treatment for patients with unresectable stage III lung cancer, as it helps prolong survival and delay disease progression. ^{1 2 3 4 5}

What safety data exists for the combination of immunotherapy and radiation in lung cancer treatment?

Safety data for the combination of durvalumab (an anti-PD-L1 therapy) and radiation therapy in lung cancer treatment is available from several studies. A meta-analysis has investigated the safety and efficacy of durvalumab in various solid tumors. A phase 1/2 trial assessed the preliminary safety and efficacy of durvalumab combined with radiotherapy. The DUART trial is specifically assessing the safety and tolerability of durvalumab following radiotherapy in patients with unresectable stage III NSCLC who are ineligible for chemotherapy. These studies provide insights into the safety profile of this treatment combination. ^{1 5 6 7 8}

Is the combination of immunotherapy (Durvalumab) and radiation therapy safe for humans?

Research shows that Durvalumab, an immunotherapy drug, has been studied for safety in combination with radiation therapy in various cancers, including lung cancer. These studies generally indicate that the treatment is safe, although some patients may experience side effects, which are common in cancer treatments. ^{1 5 6 7 8}

Is the drug Durvalumab combined with Stereotactic Radiation Therapy a promising treatment for lung cancer?

Yes, Durvalumab combined with Stereotactic Radiation Therapy is a promising treatment for lung cancer. Studies show that patients treated with Durvalumab had longer survival times and better outcomes compared to those who did not receive it. This combination has been shown to improve the chances of controlling the disease and extending life for patients with certain types of lung cancer. ^{1 3 5 6 9}

How is the treatment of Durvalumab and Stereotactic Radiation Therapy for lung cancer different from other treatments?

This treatment combines Durvalumab, an immunotherapy drug that helps the immune system attack cancer cells, with Stereotactic Radiation Therapy, a precise form of radiation that targets tumors. This combination is unique because it leverages the immune system alongside targeted radiation, potentially offering better outcomes for patients with certain types of lung cancer compared to traditional chemotherapy and radiation alone. ^{1 3 5 6 9}

Research Team

Shahed Badiyan, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

Adults over 18 with advanced non-small cell lung cancer, who haven't had prior radiation or surgery in the treatment area and have at least one symptomatic metastatic site. They must be able to consent, follow study protocol, have a life expectancy over six months, and use effective birth control. Exclusions include certain medication uses, unresolved toxicities from past therapies, major surgeries within the last month, organ transplants, pregnancy or nursing.

Inclusion Criteria

Capable of giving signed informed consent and willing and able to comply with the protocol for the duration of the study

My body weight is over 30 kg.

My cancer was advanced from the start or came back after treatment.

Exclusion Criteria

Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study

Participation in another clinical study with an investigational product during the last 3 months

I have a history of certain medical conditions or infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Durvalumab and stereotactic radiotherapy, either on a SAbR schedule every other day or a PULSAR schedule every four weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months post-treatment

Long-term follow-up

Participants continue routine follow-up with their physicians per standard of care after the 2-year follow-up period

Treatment Details

Interventions

• Durvalumab
• Stereotactic Radiation Therapy

Trial Overview The trial is testing Durvalumab combined with stereotactic radiotherapy on patients with advanced NSCLC. It aims to see how this affects their quality of life and cancer outcomes. Patients are randomly assigned to receive radiotherapy either every other day (SAbR) or every four weeks (PULSAR), alongside Durvalumab for two years.

Participant Groups

Group I: Personalized Ultra-fractionated Stereotactic Radiotherapy (PULSAR) plus Durvalumab arm Experimental Treatment 2 Interventions

PULSAR with each radiation treatment fraction delivered every 4 weeks

Group II: Stereotactic Ablative Radiotherapy (SAbR) Arm plus Durvalumab arm Active Control 2 Interventions

SAbR with each radiation treatment fraction delivered every other day

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

In a study of 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

In a study involving 576 patients with unresectable stage III non-small cell lung cancer (NSCLC), the PD-L1 inhibitor durvalumab showed a favorable safety profile, with only 22.7% of patients experiencing adverse events, primarily mild esophagitis.

Durvalumab treatment after concurrent chemoradiotherapy (cCRT) resulted in consistent outcomes across both PD-L1 positive and negative patients, indicating its potential as a standard care option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. Avrillon, V., Daniel, C., Boisselier, P., et al.[2022]

In a study of 56 patients with non-small cell lung cancer (NSCLC), those treated with intensity-modulated radiation therapy (IMRT) had a significantly lower incidence of grade 2 or higher radiation pneumonitis (RP) compared to those treated with three-dimensional conformal radiotherapy (3D-CRT), with rates of 27.0% versus 64.0%.

The study identified that the radiation technique (IMRT vs. 3D-CRT) and the volume of lung receiving radiation (V20) were significant risk factors for developing RP, suggesting that IMRT may be a safer option for reducing RP in NSCLC patients undergoing concurrent chemoradiotherapy followed by durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. Masuo, M., Shinohara, E., Kitano, M., et al.[2023]

In a study of 68 patients with locally advanced non-small cell lung cancer treated with intensity-modulated radiotherapy (IMRT), the administration of durvalumab significantly improved distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), with hazard ratios of 0.31, 0.33, and 0.32 respectively.

The study also found that while grade 2 or higher radiation pneumonitis (RP) was associated with worse DMFS, reducing the incidence of RP could enhance patient outcomes, highlighting the importance of managing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. Yamamoto, T., Tsukita, Y., Katagiri, Y., et al.[2022]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

In a study involving 10 patients receiving palliative radiotherapy (RT) combined with durvalumab, the treatment was well tolerated, with only 50% experiencing mild to moderate adverse events, primarily G2 mucositis, and no severe adverse events reported.

The treatment showed promising efficacy, with a 60% objective response rate in evaluable lesions and a significant decrease in tumor growth rate after RT, indicating that durvalumab combined with RT may effectively reduce tumor size in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Levy, A., Massard, C., Soria, JC., et al.[2022]

In a study of 271 patients with unresectable stage III NSCLC, intensity modulated proton therapy (IMPT) resulted in a significantly lower incidence of severe lymphopenia (67% in IMRT vs. 47% in IMPT) and anemia (26% in IMRT vs. 9% in IMPT) during concurrent chemo-radiotherapy.

Patients receiving IMPT also had a better performance status after treatment and a higher likelihood of continuing to adjuvant durvalumab therapy (74% vs. 52%), suggesting that IMPT may enhance overall treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy. Cortiula, F., Hendriks, LEL., Wijsman, R., et al.[2023]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In the Phase 3 PACIFIC study involving 713 patients with unresectable stage III non-small-cell lung cancer (NSCLC), the anti-PD-L1 agent durvalumab significantly improved median progression-free survival (17.2 months vs. 5.6 months for placebo) and overall survival (not reached vs. 28.7 months for placebo).

While durvalumab showed a slight increase in grade 3 or 4 toxicity (30.5% vs. 26.1% for placebo), its efficacy in prolonging survival justifies its use, leading to its licensing for this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). Patel, P., Alrifai, D., McDonald, F., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Nationwide Real-Life Safety and Treatment Exposure Data on Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III, Locally Advanced, Non-small Cell Lung Cancer: Analysis of Patients Enrolled in the French Early Access Program. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. [2022]

5. England pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Proton and photon radiotherapy in stage III NSCLC: Effects on hematological toxicity and adjuvant immune therapy. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). [2023]