To Evaluate the Efficacy/Safety of Osimertinib Prior to CRT and Maintenance of it With Stage III, Unresectable NSCLC With EGFR Mutations

NCT06194448 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: D516AC000032023-507798-16-00
• Study Type: interventional
• Target: 76
• Locations: 9 countries
• Sites: 39

Brief Summary

The purpose of this study is to measure efficacy and safety of osimertinib as induction therapy prior to curative intent CRT and maintenance osimertinib in adult patients with Stage III, unresectable NSCLC with common EGFR mutations (exon 19 deletion or L858R).

Conditions

Lung Cancer

Keywords

EGFR +; Unresectable Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• PFS (Progression-Free Survival)

  PFS is defined as the time from date of first dose until progression per RECIST 1.1 as assessed by the investigator at the local site, or death due to any cause.

  Assessed from date of first dose to progression (up to a maximum of approximately 4 years)

Secondary Outcomes (4)

• ORR (Objective Response Rate)

  Assessed during the induction phase of the study, scans are carried out at baseline and week 8 (plus or minus visit window).

• DCR (Disease Control Rate)

  Assessed during the induction phase of the study, scans are carried out at baseline and week 8 (plus or minus visit window).

• OS (Overall Survival)

  Assessed from first dose to end of study or death (up to a maximum of approximately 4 years)

• EFS (Event-Free Survival)

  Assessed from first dose until a progression event or death (up to a maximum of approximately 4 years)

Other Outcomes (1)

• AEs

  from signing ICF to 28 days after last dose or end of study (up to a maximum of approximately 4 years)

Study Arms (1)

Open-Label Osimertinib Induction Treatment

EXPERIMENTAL

Patients will receive open-label osimertinib induction treatment for 8 weeks (± 1 week window to account for patient variability and CRT scheduling), followed by CRT treatment for 6 weeks (± 1 week) and then osimertinib maintenance treatment until RECIST 1.1-defined radiological progression by investigator unless there is evidence of unacceptable toxicity or if the patient requests to stop the study treatment.

Drug: Osimertinib; Drug: Cisplatin or Carboplatin; Pemetrexed or Paclitaxel; Drug: Radiation

Interventions

Osimertinib DRUG

80 mg daily (or 40 mg daily for dose reduction)

Also known as: Tagrisso, AZD9291

Open-Label Osimertinib Induction Treatment

Cisplatin or Carboplatin; Pemetrexed or Paclitaxel DRUG

Pemetrexed (500 mg/m2 to be administered on Day 1 of every 3-week cycle for 2 cycles) or Paclitaxel (175 mg/m2 on Day 1 of every 3-week cycle for 2 cycles) PLUS Cisplatin (75 mg/m2) or Carboplatin (AUC5) to be administered on Day 1 of every 3--week cycle for 2 cycles

Open-Label Osimertinib Induction Treatment

Radiation DRUG

Patients must have received a total dose of radiation of 60 Gy ± 10% (54 to 66 Gy) as part of the chemoradiation therapy. It is recommended but not required that patients have a: * Mean lung dose \< 20 Gy and/or V20 \< 35% * Mean oesophagus dose \< 34 Gy * Heart V50 \< 25%, V30 \< 50%, and V45 \< 35%

Open-Label Osimertinib Induction Treatment

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent form.
• Patients with histologically documented NSCLC of predominantly non-squamous, squamous, and adenosquamous pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology). It is recommended but not required that except for overt cT4 disease, nodal status N2, or N3 should have been proven by biopsy, via endobronchial ultrasound, mediastinoscopy, thoracoscopy, or in absence of biopsy, should have been confirmed with whole body 18FDG PET plus contrast-enhanced CT in addition to or in combination with PET.
• Patient who are eligible for and - planning to undergo CCRT or SCRT treatment.
• Patients who had recurred from Stage I/II/III after complete surgery or had gross incomplete resections can be included if they didn't receive treatment with any chemotherapy, radiation therapy, immunotherapy, targeted therapy, or investigational agents.
• Demonstrate absence of HCV co-infection or history of HCV co-infection
• Demonstrate absence of HIV co-infection
• Patients with active HBV infection are eligible if they are:
• Receiving anti-viral treatment for at least 6 weeks prior to study treatment, HBV DNA is suppressed to \<100 IU/mL and transaminase levels are below ULN.
• Participants with a resolved or chronic HBV infection are eligible if they are:
• Negative for HBsAg and positive for hepatitis B core antibody \[anti-HBc IgG or total anti-HBc Ab\]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment or
• Positive for HBsAg, but for \> 6 months have had transaminases levels below ULN and HBV DNA levels below \<100 IU/mL (i.e., are in an inactive carrier state). In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment.
• Demonstrate absence of HBV/ HCV co-infection
• Undetectable viral RNA load for 6 months
• CD4+ count of \>350 cells/μL
• No history of AIDS-defining opportunistic infection within the past 12 months

You may not qualify if:

• Any presence of small cell and mixed small-cell and non-small cell histology.
• Past medical history of ILD/pneumonitis, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD/pneumonitis.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator may be included after consultation with the AstraZeneca medical monitor (eg, hearing loss).
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection (eg, patients receiving treatment for infection, including HCV, HIV, and tuberculosis) or active uncontrolled HBV infection.
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include adequately resected non-melanoma skin cancer and curatively treated in situ disease. Patients who have received RT with overlapping fields (eg, cured breast cancer) should be excluded.
• Patient meets any of the following cardiac criteria:
• Mean resting QTc \> 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value.
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block and second-degree heart block. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on the investigator judgement with cardiologist consultation recommended.
• History of QT prolongation associated with other medications that required discontinuation of that medication.
• Congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death under 40 years of age in first-degree relatives or patients with any factors that increase the risk of QTc prolongation/arrhythmic events such as electrolyte abnormalities, heart failure or any concomitant medication known to prolong the QT interval and cause TdP.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 × 10\^9/L
• Platelet count \<100 × 10\^9/L
• Haemoglobin \<90 g/L

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (39)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Palo Alto, California, 94304, United States

Location

Research Site

Beijing, 100021, China

Location

Research Site

Changsha, 410013, China

Location

Research Site

Guangzhou, 510060, China

Location

Research Site

Hangzhou, 310022, China

Location

Research Site

Harbin, 150081, China

Location

Research Site

Hefei, 230001, China

Location

Research Site

Jinan, 250117, China

Location

Research Site

Nanning, 530021, China

Location

Research Site

Shanghai, 200032, China

Location

Research Site

Tianjin, 300060, China

Location

Research Site

Wuhan, 430022, China

Location

Research Site

Wuhan, 430071, China

Location

Research Site

Zhengzhou, 450052, China

Location

Research Site

Haifa, 31096, Israel

Location

Research Site

Jerusalem, 91031, Israel

Location

Research Site

Tel Aviv, 62748, Israel

Location

Research Site

Cheongju-si, 28644, South Korea

Location

Research Site

Seongnam-si, 13620, South Korea

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Suwon, 16247, South Korea

Location

Research Site

Barcelona, 08003, Spain

Location

Research Site

Donostia / San Sebastian, 20014, Spain

Location

Research Site

Granada, 18016, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Tainan, 704, Taiwan

Location

Research Site

Taipei, 11217, Taiwan

Location

Research Site

Bangkok, 10210, Thailand

Location

Research Site

Bangkok, 10330, Thailand

Location

Research Site

Chiang Rai, 57000, Thailand

Location

Research Site

Hat Yai, 90110, Thailand

Location

Research Site

Khon Kaen, 40002, Thailand

Location

Research Site

Ankara, 06010, Turkey (Türkiye)

Location

Research Site

Yenimahalle, 06560, Turkey (Türkiye)

Location

Research Site

Hanoi, 100000, Vietnam

Location

Research Site

Ho Chi Minh City, 700000, Vietnam

Location

Related Publications (1)

• Aredo JV, Peled N, Arriola E, Wakelee H, Ahn MJ, Kwint MH, Taylor R, van der Gronde T, Nasirova F, Chen M. Osimertinib before and after chemoradiotherapy for unresectable stage III EGFR-mutated NSCLC: NEOLA Trial Protocol. Future Oncol. 2025 Dec;21(29):3731-3737. doi: 10.1080/14796694.2025.2587569. Epub 2025 Nov 14.

  PMID: 41236484 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

osimertinib; Cisplatin; Carboplatin; Pemetrexed; Paclitaxel; Radiation

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients will receive open-label osimertinib induction treatment for 8 weeks (± 1 week window to account for patient variability and CRT scheduling), followed by CRT treatment for 6 weeks (± 1 week) and then osimertinib maintenance treatment until RECIST 1.1-defined radiological progression by investigator unless there is evidence of unacceptable toxicity or if the patient requests to stop the study treatment.

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 8, 2024
• Study Start: April 21, 2024
• Primary Completion (Estimated): July 7, 2026
• Study Completion (Estimated): July 7, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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 refer 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.

Locations

CN (13); TH (5); ES (4); TW (2); KR (6); TU (2); IL (3); US (2); VN (2)