121 Participants Needed

Multiple Therapies for Stage III Non-Small Cell Lung Cancer

Recruiting at 217 trial locations
RS
Overseen ByReference Study ID Number: BO42777 https://forpatients.roche.com/
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This trial is testing different treatments to see how well they work and how safe they are. It focuses on patients with advanced lung cancer that cannot be removed by surgery and have specific biological markers. The goal is to find out if these treatments can stop the cancer from growing or spreading and improve patients' health.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it does exclude participants who are on certain treatments like systemic immunosuppressive medications or concurrent cancer therapies, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab (Imfinzi) for treating stage III non-small cell lung cancer?

Research shows that Durvalumab, when used after chemoradiotherapy, significantly improves progression-free survival and overall survival in patients with stage III non-small cell lung cancer compared to a placebo. This suggests that Durvalumab can be an effective treatment option for this condition.12345

Is the treatment generally safe for humans?

Durvalumab, one of the treatments being considered, has been shown to increase the risk of immune-related side effects, particularly pneumonitis (inflammation of the lungs), which can be serious and potentially life-threatening. Safety data from various studies indicate that while durvalumab is used in treating certain cancers, it is important to monitor for these side effects.46789

How is the drug combination of Alectinib, Durvalumab, Entrectinib, and Pralsetinib unique for treating Stage III non-small cell lung cancer?

This drug combination is unique because it includes multiple targeted therapies and immunotherapy agents, such as Durvalumab, which has shown improved survival in patients with unresectable Stage III non-small cell lung cancer when used after chemoradiotherapy. The combination of these drugs may offer a novel approach by targeting different pathways involved in cancer growth and immune evasion.510111213

Research Team

CT

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with Stage III Non-Small Cell Lung Cancer (NSCLC) who can swallow pills, have had prior chemo and radiotherapy without disease progression, and are expected to live at least 12 weeks. They must not be pregnant or planning pregnancy, agree to use contraception, and have no history of certain bone disorders or severe allergies.

Inclusion Criteria

My cancer has a confirmed ALK fusion from an approved test.
My lung cancer is at an advanced stage and cannot be removed by surgery.
My cancer did not worsen during or after platinum-based chemo.
See 14 more

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.
I have severe side effects from previous treatments that haven't improved.
I have a family or personal history of bone disorders.
See 43 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive entrectinib 600 mg orally once daily or durvalumab 1500 mg IV every 4 weeks, depending on cohort, until completion of treatment period or other specified conditions

1-3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Alectinib
  • Durvalumab
  • Entrectinib
  • Pralsetinib
Trial OverviewThe study tests the effectiveness and safety of Entrectinib, Durvalumab, Alectinib in NSCLC patients with specific biomarkers. It requires a PET/CT scan for staging and uses electronic patient-reported outcomes for monitoring.
Participant Groups
4Treatment groups
Experimental Treatment
Active Control
Group I: Cohort A2: ROS 1-positive (entrectinib arm)Experimental Treatment1 Intervention
Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment.
Group II: Cohort A1: ALK-Positive (alectinib arm)Experimental Treatment1 Intervention
Participants will receive alectinib 600 mg orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first
Group III: Cohort A2: ROS 1-positive (durvalumab arm)Active Control1 Intervention
Participants will receive 1500 mg of IV durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment.
Group IV: Cohort A1: ALK-positive (durvalumab arm)Active Control1 Intervention
Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first

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

🇺🇸
Approved in United States as Alecensa for:
  • Metastatic ALK-positive non-small cell lung cancer (NSCLC)
  • Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC
🇪🇺
Approved in European Union as Alecensa for:
  • Metastatic ALK-positive non-small cell lung cancer (NSCLC)
  • Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Find a Clinic Near You

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials
2,482
Recruited
1,107,000+
Headquarters
Basel, Switzerland
Known For
Precision medicine
Top Products
Avastin, Herceptin, Rituxan, Accu-Chek
Dr. Levi Garraway profile image

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker profile image

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

The CheckMate73L trial is investigating the effectiveness of combining nivolumab with concurrent chemoradiotherapy (cCRT) followed by additional nivolumab with or without ipilimumab, compared to the standard treatment of cCRT followed by durvalumab, in patients with untreated stage III non-small-cell lung cancer (NSCLC).
The primary goals of the study are to evaluate progression-free survival (PFS) and overall survival (OS), with results expected to provide insights into whether the combination therapy offers better outcomes than the current standard of care.
CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer.De Ruysscher, D., Ramalingam, S., Urbanic, J., et al.[2022]
Durvalumab, a PD-L1 inhibitor, has shown promising results in increasing progression-free survival and objective response rates in patients with inoperable and locally advanced stage III non-small cell lung cancer, based on interim results from a phase III trial.
The significant benefits observed suggest that durvalumab could potentially become the standard treatment for these patients in the United States.
Durvalumab Promising for NSCLC.[2019]
In a systematic review and network meta-analysis of first-line treatments for metastatic nonsquamous non-small-cell lung cancer (NSq-NSCLC), the combination of pembrolizumab, pemetrexed, and platinum showed a statistically significant improvement in overall survival compared to various other regimens, with hazard ratios ranging from 0.42 to 0.62.
This combination therapy had a 95.6% probability of being the most effective treatment option for overall survival in patients without known targetable mutations, indicating its strong potential as a first-line treatment for this type of lung cancer.
Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis.Frederickson, AM., Arndorfer, S., Zhang, I., et al.[2022]

References

CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer. [2022]
Durvalumab Promising for NSCLC. [2019]
Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. [2022]
Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. [2022]
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]
Mocetinostat in Combination With Durvalumab for Patients With Advanced NSCLC: Results From a Phase I/II Study. [2023]
Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]
DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]
Open issues in the therapeutic management of unresectable stage III NSCLC in the immunotherapy era. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Role of immunotherapy in stage III nonsmall cell lung cancer. [2020]
The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer. [2022]
13.United Statespubmed.ncbi.nlm.nih.gov
Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial. [2022]