Monalizumab or Oleclumab with Durvalumab and Radiation for Lung Cancer

No longer recruiting at 67 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressive medications

Disqualifiers: Metastatic disease, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: 17

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding the drug durvalumab to certain types of radiation therapy, along with other drugs like monalizumab or oleclumab, is safe and effective for treating non-small cell lung cancer (NSCLC) that has not spread beyond nearby tissue or lymph nodes. Durvalumab and the other drugs are types of immunotherapy, which help the body's immune system fight cancer cells. People with stage II-III non-small cell lung cancer who cannot undergo surgery might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that you cannot use immunosuppressive medication within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that durvalumab is generally safe for people with various solid cancers. Studies have found that it has a manageable safety profile when used alone or with other treatments. Some patients have experienced mild to moderate side effects, such as tiredness and nausea.

A trial that combined monalizumab with durvalumab and chemotherapy found the combination to be well-tolerated. Most side effects were mild, including fatigue and a slight cough.

When oleclumab was combined with durvalumab, it demonstrated minimal clinical activity across different tumor types. This means the treatment caused few side effects but did not significantly shrink tumors.

Overall, these treatments have been tested before, and while side effects can occur, they are usually not severe. However, more research is needed, especially since this trial remains in the early stages. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because they combine innovative immunotherapies with radiation to potentially enhance treatment effectiveness. Unlike standard chemotherapy, which directly targets and kills cancer cells, durvalumab, oleclumab, and monalizumab are designed to boost the body’s immune response to fight cancer. Durvalumab works as a checkpoint inhibitor, blocking a specific protein that prevents the immune system from attacking cancer cells. Oleclumab and monalizumab further enhance this immune response by targeting other proteins involved in immune suppression, potentially leading to a more comprehensive attack on the tumor. This combination approach could offer more personalized and effective treatment options for patients with lung cancer.

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

Research has shown that combining durvalumab with other treatments can help the immune system fight cancer more effectively. In this trial, participants may receive durvalumab with either monalizumab or oleclumab as part of different treatment arms. Adding monalizumab to durvalumab has been linked to a higher success rate in shrinking tumors, with 35.5% of patients responding well compared to 17.9% with durvalumab alone. Similarly, combining oleclumab with durvalumab increases the success rate to 30.0%. Both combinations have shown promise in reducing the risk of cancer growth or spread and may improve survival rates. These findings suggest that these combinations could effectively treat non-small cell lung cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Steven H Lin

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage II-III non-small cell lung cancer (NSCLC) that can't be removed by surgery. They must have a specific level of tumor protein called PD-L1, good organ function, and no liver or kidney damage. Participants need to be physically able to undergo the treatments (ECOG 0-2), have sufficient lung function, and weigh over 30 kg.

Inclusion Criteria

You had a medical check-up within the month before signing up for the study.

Your white blood cell count is at least 1500 cells per cubic millimeter.

I need extra oxygen due to my tumor but the amount has been stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive durvalumab and either monalizumab or oleclumab with radiation therapy

52 weeks

13 cycles, each 4 weeks long

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months for year 1, every 4 months for year 2

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Fractionated Stereotactic Radiation Therapy
• Hypofractionated Radiation Therapy
• Radiation Therapy

Trial Overview The ARCHON-1 trial is testing if adding durvalumab to standard radiation therapy improves outcomes in NSCLC patients. It's also comparing the effects when either monalizumab or oleclumab are added into this treatment mix. The study will look at different doses of radiation and how well these combinations work together.

How Is the Trial Designed?

Group I: Arm IV (durvalumab, oleclumab, standard RT) Experimental Treatment 6 Interventions

Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Patients also receive oleclumab IV over 60 minutes on days 1 and 15 of cycles 1-2, then on day 1 of cycles thereafter. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

Group II: Arm III (durvalumab, monalizumab, standard RT) Experimental Treatment 6 Interventions

Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes and monalizumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

Group III: Arm II (CLOSED) (Durvalumab and standard RT) Experimental Treatment 5 Interventions

Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo conventionally fractionated radiation therapy 1 fraction per day, 5 days per week for 30 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

Group IV: Arm I (CLOSED) (Durvalumab and ACRT) Experimental Treatment 5 Interventions

Starting 2 weeks prior to radiation therapy, patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 4 weeks for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo ACRT 1 fraction per day, 5 days per week for 15 fractions. Patients also undergo brain MRI or CT scan during screening and as clinically indicated, chest CT scans on study and during follow up, and collection of blood samples during screening and on study.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

In a phase II study involving 189 patients with unresectable stage III non-small-cell lung cancer, combining durvalumab with either oleclumab or monalizumab significantly improved the overall response rate (ORR) and progression-free survival (PFS) compared to durvalumab alone.

The safety profile of the combination therapies was similar to durvalumab alone, with no new significant safety concerns, indicating that these combinations could be promising options for further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COAST: An Open-Label, Phase II, Multidrug Platform Study of Durvalumab Alone or in Combination With Oleclumab or Monalizumab in Patients With Unresectable, Stage III Non-Small-Cell Lung Cancer. Herbst, RS., Majem, M., Barlesi, F., 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 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]

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 of 14 patients with stage III NSCLC receiving Atezolizumab after chemoradiotherapy, 57% developed pneumonitis, indicating a significant risk associated with this treatment approach.

The onset of pneumonitis occurred on average 2.45 months after starting Atezolizumab, suggesting that monitoring for this side effect is crucial in patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumonitis in Non-Small Cell Lung Cancer Patients Receiving Atezolizumab Post Chemo-Radiation. Saade, LJ., Tfayli, A.[2023]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., et al.[2022]

Citations

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A phase II trial of monalizumab in combination with ... Primary endpoints include 1-year progression-free survival, safety, and tolerability. Secondary endpoints include objective response rate, 1- ...

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NCT05221840 | A Global Study to Assess the Effects of ... This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination ...

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PACIFIC-9: Phase III trial of durvalumab + oleclumab or ... Objective response rate (ORR) was greater with durvalumab plus oleclumab (30.0%) and durvalumab plus monalizumab (35.5%) vs durvalumab alone (17.9%) [44].

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Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

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Study Details | NCT03822351 | Durvalumab Alone or in ... The purpose of this study is to compare the clinical activity of durvalumab alone vs durvalumab in combination with novel agents. The overall study goal is ...

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NCT02671435 | A Study of Durvalumab (MEDI4736) and ... This is a multicenter, open-label, dose-escalation, dose-exploration and dose-expansion study to evaluate the safety, tolerability, antitumor activity, ...

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NCT03801902 | Testing the Safety of Adding Either ... This phase I trial studies the safety of adding durvalumab to accelerated hypofractionated radiation therapy (ACRT) or conventionally fractionated radiation ...

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A pharmacovigilance analysis of post-marketing safety ... This study aimed to systematically evaluate the safety of durvalumab through data mining of the US Food and Drug Administration Adverse Event Reporting System ...