Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03944772
- Lead Sponsor
- AstraZeneca
- Brief Summary
Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.
- Detailed Description
This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required.
This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 247
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Module 3: Osimertinib + Necitumumab Necitumumab The patients in this group will receive osimertinib taken in combination with necitumumab Module 4: Carboplatin + Pemetrexed + Durvalumab) Durvalumab The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab. Module 4: Carboplatin + Pemetrexed + Durvalumab) Carboplatin The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab. Module 4: Carboplatin + Pemetrexed + Durvalumab) Pemetrexed The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab. Module 5: Osimertinib + Alectinib Alectinib The patients in this group will receive osimertinib taken in combination with alectinib Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. Pemetrexed The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin). Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. Cisplatin The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin). Module 9: Osimertinib + Selumetinib Osimertinib The patients in this group will receive osimertinib taken in combination with selumetinib Module 9: Osimertinib + Selumetinib Selumetinib The patients in this group will receive osimertinib taken in combination with selumetinib Module 10: Osimertinib + datopotamab deruxtecan Osimertinib The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan. Module 10: Osimertinib + datopotamab deruxtecan Datopotamab deruxtecan The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan. Module 1: Osimertinib + Savolitinib Osimertinib The patients in this group will receive osimertinib taken in combination with savolitinib Module 1: Osimertinib + Savolitinib Savolitinib The patients in this group will receive osimertinib taken in combination with savolitinib Module 2: Osimertinib + Gefitinib Osimertinib The patients in this group will receive osimertinib taken in combination with gefitinib Module 2: Osimertinib + Gefitinib Gefitinib The patients in this group will receive osimertinib taken in combination with gefitinib Module 3: Osimertinib + Necitumumab Osimertinib The patients in this group will receive osimertinib taken in combination with necitumumab Module 5: Osimertinib + Alectinib Osimertinib The patients in this group will receive osimertinib taken in combination with alectinib Module 6: Osimertinib + Selpercatinib Osimertinib The patients in this group will receive osimertinib taken in combination with selpercatinib Module 6: Osimertinib + Selpercatinib Selpercatinib The patients in this group will receive osimertinib taken in combination with selpercatinib Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin Durvalumab The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab. Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin Carboplatin The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab. Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin Etoposide The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab. Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin Cisplatin The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab. Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. Osimertinib The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin). Module 8: Osimertinib + Pemetrexed + Carboplatin or Cisplatin. Carboplatin The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) Measured from first dose until confirmed response or progression. For each patient this is expected to be 3 months on average The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) Measured from first dose until progression. For each patient this is expected to be 6 months on average The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
Duration of response (DoR) Measured from response until progression. For each patient this is expected to be 6 months on average The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).
Overall survival (OS) Measured from first dose until death or final cohort data cut-off. For each patient this is expected to be 20 months on average The time from the date of the first dose of study treatment until death due to any cause.
Plasma/serum concentrations of therapeutic agents Pre-dose and serial post-dose blood samples (1 hour, 2 hours, 4 hours, 6 hours, 8 hours) on Day 15 of Cycle 1 for alectinib and selpercatinib only. Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents
Incidence of Treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v5 Continuously from first dose to end of safety follow up after study treatment discontinuation (approximately up to 21 Months) To evaluate safety and tolerability of each study treatment
Trial Locations
- Locations (1)
Research Site
🇸🇪Stockholm, Sweden