Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
ORCHARD
A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.
3 other identifiers
interventional
247
9 countries
47
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started Jun 2019
Longer than P75 for phase_2 nonsmall-cell-lung-cancer
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 29, 2019
CompletedFirst Posted
Study publicly available on registry
May 10, 2019
CompletedStudy Start
First participant enrolled
June 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 6, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 6, 2025
CompletedJanuary 30, 2025
December 1, 2024
5.9 years
April 29, 2019
January 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Objective response rate (ORR)
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).
Measured from first dose until confirmed response or progression. For each patient this is expected to be 3 months on average
Secondary Outcomes (6)
Progression-free survival (PFS)
Measured from first dose until progression. For each patient this is expected to be 6 months on average
Duration of response (DoR)
Measured from response until progression. For each patient this is expected to be 6 months on average
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
Plasma/serum concentrations of therapeutic agents
Pre-dose and 1 hour post-dose blood samples on Day 1 of Cycles 1, 3 (Cycle 2 for durvalumab), 6 for all therapeutic agents and a sample at the 90-day safety follow up for durvalumab only. (One Cycle = 21 or 28 days, depending on treatment).
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.
- +1 more secondary outcomes
Study Arms (11)
Module 1: Osimertinib + Savolitinib
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with savolitinib
Module 2: Osimertinib + Gefitinib
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with gefitinib
Module 3: Osimertinib + Necitumumab
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with necitumumab
Module 4: Carboplatin + Pemetrexed + Durvalumab)
EXPERIMENTALThe patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.
Observational Cohort: No study drug
NO INTERVENTIONPatients 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.
Module 5: Osimertinib + Alectinib
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with alectinib
Module 6: Osimertinib + Selpercatinib
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with selpercatinib
Module 7: Etoposide + Durvalumab + Carboplatin or Cisplatin
EXPERIMENTALThe 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.
EXPERIMENTALThe patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).
Module 9: Osimertinib + Selumetinib
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with selumetinib
Module 10: Osimertinib + datopotamab deruxtecan
EXPERIMENTALThe patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.
Interventions
Osimertinib given orally at 80 mg once daily
Savolitinib will be given orally at 300 mg or 600mg once daily
Gefitinib given orally at 250 mg once daily
Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle
Durvalumab given IV at 1500 mg on Day 1 of every cycle
Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles
Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle
Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.
Selpercatinib given orally at 160mg twice daily
Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment
Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.
Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle
Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.
Eligibility Criteria
You may qualify if:
- NSCLC with the following features:
- Locally advanced or metastatic disease (ie, advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry.
- Histologically or cytologically confirmed adenocarcinoma of the lung (patients with mixed histology are eligible if adenocarcinoma is the predominant histology) harboring EGFR mutation(s) known to be associated with EGFR TKI sensitivity at diagnosis. Any histologically identifiable component of neuroendocrine transformation to SCLC or large cell NEC is required for treatment under Module 7.
- Received only one line of therapy, with single-agent osimertinib, for advanced NSCLC, with clinical benefit as judged by investigator discretion.
You may not qualify if:
- Evidence of radiological disease progression on first-line monotherapy with osimertinib 80 mg po QD.
- Suitable for a mandatory biopsy defined as having an accessible tumor; by whichever modality the site uses and, ideally, confirmed by the person who will perform the procedure; and a stable clinical condition that will allow the patient to tolerate the procedure. The biopsy should be performed within 60 days of the planned first dose of study treatment.
- Patients must have measurable disease per RECIST 1.1, as defined by at least 1 lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter (except lymph nodes which must have a short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements. Previously irradiated lesions or a lesion in the field of radiation should not be used as measurable disease unless the lesion(s) has/have demonstrated unequivocal disease progression by RECIST 1.1. Target lesions should not be used for the baseline tumour biopsy, unless there are no other lesions suitable for biopsy and they fulfil requirements.
- Adequate coagulation parameters, defined as:
- International Normalisation Ratio (INR) \< 1.5 × upper limit of normal (ULN) and activated partial thromboplastin time \< 1.5 × ULN unless patients are receiving therapeutic anti-coagulation which affects these parameters.
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- Patients whose disease has progressed within the first 3 months of osimertinib treatment (refractory to osimertinib treatment).
- Patients must not have experienced a toxicity(-ies) that led to permanent discontinuation or dose reduction of prior osimertinib.
- (a) Patients who had dose reductions in the past, but were receiving a full dose of osimertinib at the time of pre-screening should be discussed with the Study Physician.
- Any unresolved toxicities from prior osimertinib treatment greater than CTCAE Grade 1 at the time of starting study treatment.
- Patients should not have discontinued osimertinib \>60 days prior to the first dose of study treatment.
- Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Absolute neutrophil count \< 1.5 × 109/L.
- Platelet count \< 100 × 109/L.
- Haemoglobin \< 9 g/dL.
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (47)
Research Site
Duarte, California, 91010, United States
Research Site
Los Angeles, California, 90048, United States
Research Site
Sacramento, California, 95817, United States
Research Site
Santa Monica, California, 90404, United States
Research Site
New Haven, Connecticut, 06510, United States
Research Site
Chicago, Illinois, 60612, United States
Research Site
Baltimore, Maryland, 21224, United States
Research Site
Boston, Massachusetts, 02114, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
Grand Rapids, Michigan, 49503, United States
Research Site
New York, New York, 10017, United States
Research Site
New York, New York, 10032, United States
Research Site
Portland, Oregon, 97239, United States
Research Site
Pittsburgh, Pennsylvania, 15232, United States
Research Site
Houston, Texas, 77030, United States
Research Site
Seattle, Washington, 98109, United States
Research Site
Odense C, 5000, Denmark
Research Site
Catania, 95123, Italy
Research Site
Napoli, 80131, Italy
Research Site
Orbassano, 10043, Italy
Research Site
Padua, 35128, Italy
Research Site
Varese, 21100, Italy
Research Site
Chūōku, 104-0045, Japan
Research Site
Fukuoka, 812-8582, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Nagoya, 464-8681, Japan
Research Site
Osaka, 541-8567, Japan
Research Site
Wakayama, 641-8510, Japan
Research Site
Amsterdam, 1066 CX, Netherlands
Research Site
Amsterdam, 1081 HV, Netherlands
Research Site
Maastricht, 6229 HX, Netherlands
Research Site
Nijmegen, 6525 GA, Netherlands
Research Site
Rotterdam, 3015GD, Netherlands
Research Site
Drammen, 3004, Norway
Research Site
Oslo, N-0310, Norway
Research Site
Trondheim, 7030, Norway
Research Site
Seongnam-si, 13620, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
A Coruña, 15006, Spain
Research Site
Barcelona, 08025, Spain
Research Site
Barcelona, 08036, Spain
Research Site
Madrid, 28041, Spain
Research Site
Madrid, 28046, Spain
Research Site
Seville, 41009, Spain
Research Site
Stockholm, 17176, Sweden
Related Publications (3)
Riess JW, de Langen AJ, Ponce S, Goldberg SB, Piotrowska Z, Goldman JW, Le X, Cho BC, Yoneshima Y, Ambrose H, Cavazzina R, Tang KH, Lau J, Yu HA. ORCHARD: Osimertinib Plus Necitumumab in Patients With Epidermal Growth Factor Receptor-Mutated Advanced Non-Small Cell Lung Cancer With a Secondary Epidermal Growth Factor Receptor Alteration Whose Disease Had Progressed on First-Line Osimertinib. JCO Precis Oncol. 2025 Jun;9:e2400818. doi: 10.1200/PO-24-00818. Epub 2025 Jun 4.
PMID: 40466026DERIVEDYu HA, Goldberg SB, Le X, Piotrowska Z, Goldman JW, De Langen AJ, Okamoto I, Cho BC, Smith P, Mensi I, Ambrose H, Kraljevic S, Maidment J, Chmielecki J, Li-Sucholeiki X, Doughton G, Patel G, Jewsbury P, Szekeres P, Riess JW. Biomarker-Directed Phase II Platform Study in Patients With EGFR Sensitizing Mutation-Positive Advanced/Metastatic Non-Small Cell Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy (ORCHARD). Clin Lung Cancer. 2021 Nov;22(6):601-606. doi: 10.1016/j.cllc.2021.06.006. Epub 2021 Jun 25.
PMID: 34389237DERIVEDSchmid S, Fruh M, Peters S. Targeting MET in EGFR resistance in non-small-cell lung cancer-ready for daily practice? Lancet Oncol. 2020 Mar;21(3):320-322. doi: 10.1016/S1470-2045(19)30859-9. Epub 2020 Feb 3. No abstract available.
PMID: 32027845DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Helena A Yu, MD
Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 29, 2019
First Posted
May 10, 2019
Study Start
June 25, 2019
Primary Completion
May 6, 2025
Study Completion
May 6, 2025
Last Updated
January 30, 2025
Record last verified: 2024-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.