Multiple Therapies for Non-Small Cell Lung Cancer
(ORCHARD Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores new treatment combinations for individuals with advanced non-small cell lung cancer who did not respond to initial osimertinib treatment, a targeted therapy. It tests various drug combinations to determine which most effectively slow the disease, while also assessing safety and side effects. The trial includes several groups: some receive different combinations of osimertinib with other drugs, and one observational group does not receive the study drugs. Individuals with advanced non-small cell lung cancer and an EGFR mutation, whose disease progressed after initial osimertinib treatment, might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to advancements in cancer treatment.
Do I have to stop taking my current medications for the trial?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Previous research found that combining etoposide, durvalumab, and either carboplatin or cisplatin was safe, with no unexpected issues. Another study showed that carboplatin with pemetrexed and durvalumab also had manageable side effects.
For osimertinib, studies suggest it is generally safe for treating non-small cell lung cancer. Adding alectinib or selpercatinib to osimertinib has been shown to be safe, with selpercatinib providing significant benefits without new safety concerns.
Combining osimertinib with pemetrexed and either carboplatin or cisplatin was reported to be tolerable. The combination of osimertinib and selumetinib is generally easy to manage. When combined with datopotamab deruxtecan, there were no new safety issues, and side effects were similar to previous findings.
Osimertinib with savolitinib showed an acceptable balance of risks and benefits. The combination with gefitinib is considered safe and effective. Lastly, combining osimertinib with necitumumab was found to be safe and tolerable, suggesting it is worth further study.
These studies provide confidence that these treatment combinations are generally well-tolerated and manageable, though individual experiences may vary.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments for non-small cell lung cancer because they combine osimertinib, a targeted therapy that specifically attacks cancer cells with certain mutations, with other promising drugs. Unlike traditional chemotherapy, which affects both healthy and cancerous cells, these combinations aim to enhance effectiveness while potentially reducing side effects. For example, osimertinib paired with alectinib targets multiple pathways that cancer cells use to grow and spread, potentially increasing treatment success. Other combinations, like osimertinib with selpercatinib or savolitinib, focus on overcoming resistance that often develops with standard treatments. These innovative approaches could offer more personalized and effective options for patients.
What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?
Research has shown that several new treatments for advanced non-small cell lung cancer hold promise. In this trial, participants will join different treatment arms to evaluate these combinations. One arm will test osimertinib with savolitinib, which has produced strong and lasting responses in patients with certain genetic changes. Another arm will evaluate osimertinib with pemetrexed and platinum-based chemotherapy, which has allowed patients to live longer without their cancer worsening compared to chemotherapy alone. Additionally, the combination of datopotamab deruxtecan with osimertinib, tested in another arm, has shown positive results in patients whose cancer continued to grow after previous treatments. The use of durvalumab with platinum-based chemotherapy and etoposide, also tested in this trial, has significantly improved survival rates compared to traditional treatments. Each treatment combination targets specific genetic markers or mechanisms, aiming to improve outcomes for patients with advanced lung cancer.35678
Who Is on the Research Team?
Helena A Yu, MD
Principal Investigator
Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Are You a Good Fit for This Trial?
This trial is for adults with advanced non-small cell lung cancer that has worsened despite first-line treatment with Osimertinib. Participants must have a specific EGFR mutation, measurable disease progression, and be able to undergo a biopsy. They should only have had Osimertinib as their prior therapy and not have experienced severe side effects or rapid disease progression on it.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive various experimental treatments based on the module they are assigned to, including combinations of osimertinib with other drugs such as alectinib, selpercatinib, and others.
Follow-up
Participants are monitored for safety and effectiveness after treatment, with assessments for progression-free survival and overall survival.
Safety Follow-up
Participants are monitored for treatment-emergent adverse events and serious adverse events.
What Are the Treatments Tested in This Trial?
Interventions
- Alectinib
- Carboplatin
- Cisplatin
- Datopotamab deruxtecan
- Durvalumab
- Etoposide
- Gefitinib
- Necitumumab
- Osimertinib
- Pemetrexed
- Savolitinib
- Selpercatinib
- Selumetinib
Osimertinib is already approved in United States, European Union for the following indications:
- Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
- Metastatic EGFR T790M mutation-positive NSCLC
- Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
- Metastatic EGFR T790M mutation-positive NSCLC
Find a Clinic Near You
Who Is Running the Clinical Trial?
AstraZeneca
Lead Sponsor
Sir Pascal Soriot
AstraZeneca
Chief Executive Officer since 2012
Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris
Dr. Cristian Massacesi
AstraZeneca
Chief Medical Officer since 2021
MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology
Pascal Soriot
AstraZeneca
Chief Executive Officer since 2012
Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris
Cristian Massacesi
AstraZeneca
Chief Medical Officer since 2021
MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology