Multiple Therapies for Non-Small Cell Lung Cancer

(ORCHARD Trial)

Recruiting at 41 trial locations

Overseen By Cancer Study Locator (For US sites only)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Osimertinib

Disqualifiers: Refractory to osimertinib, Inadequate organ function, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 6 months

247 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing several new treatments for patients with advanced lung cancer that has worsened after previous treatments. The goal is to find out if these new treatments can help when current medications stop working.

Research Team

Helena A Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA

Eligibility Criteria

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

My lung cancer cannot be cured with surgery or radiation.

My cancer has worsened despite taking osimertinib.

My lung cancer has EGFR mutations sensitive to specific treatments.

Exclusion Criteria

My blood tests show my bone marrow or organs are not working well.

I stopped or reduced osimertinib due to side effects.

My condition worsened within 3 months of starting osimertinib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

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.

6 months

Visits every 6 weeks for the first 24 weeks, then every 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments for progression-free survival and overall survival.

20 months

Visits every 6 weeks for the first 24 weeks, then every 9 weeks

Safety Follow-up

Participants are monitored for treatment-emergent adverse events and serious adverse events.

21 months

Treatment Details

Interventions

• Alectinib
• Carboplatin
• Cisplatin
• Datopotamab deruxtecan
• Durvalumab
• Etoposide
• Gefitinib
• Necitumumab
• Osimertinib
• Pemetrexed
• Savolitinib
• Selpercatinib
• Selumetinib

Trial Overview The study tests the effectiveness of various treatments like Pemetrexed, Datopotamab deruxtecan, Alectinib, among others in patients whose cancer progressed after initial Osimertinib therapy. It's designed to assess multiple treatments' safety and how well they work in different modules.

Participant Groups

Group I: Module 9: Osimertinib + Selumetinib Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with selumetinib

Group II: Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. Experimental Treatment 4 Interventions

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

Group III: Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin Experimental Treatment 4 Interventions

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

Group IV: Module 6: Osimertinib + Selpercatinib Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with selpercatinib

Group V: Module 5: Osimertinib + Alectinib Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with alectinib

Group VI: Module 4: Carboplatin + Pemetrexed + Durvalumab) Experimental Treatment 3 Interventions

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Group VII: Module 3: Osimertinib + Necitumumab Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with necitumumab

Group VIII: Module 2: Osimertinib + Gefitinib Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with gefitinib

Group IX: Module 1: Osimertinib + Savolitinib Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with savolitinib

Group X: Module 10: Osimertinib + datopotamab deruxtecan Experimental Treatment 2 Interventions

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Group XI: Observational Cohort: No study drug Active Control 1 Intervention

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice. With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

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

Approved in United States as Tagrisso for:

• 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

Approved in European Union as Tagrisso for:

• 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

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

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