Osimertinib Combined With Chemotherapy in Patients Who Had Distant Recurrence After Adjuvant Osimertinib for EGFRm Resectable SIB-IIIA NSCLC. (REVIVE)

Biomarker-Directed Treatment in Patients Who Had Distant Recurrence After Adjuvant Osimertinib for EGFRm Resectable SIB-IIIA NSCLC: A Prospective, Multi-cohort, Interventional Study (REVIVE)

This study is designed as a multi-cohort trial based on various patient biomarkers study with the potential to include new study treatment in the future. EGFR-sensitive mutation-positive patients with distant recurrence after adjuvant osimertinib treatment for EGFRm resectable SIB-IIIA NSCLC and scheduled to receive osimertinib plus chemotherapy will be enrolled in cohort 1. In this cohort, approximately 100 patients will be recruited from 25 sites in China. The enrolment period is planned to be approximately 16 months.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Osimertinib+cisplatin or carboplatin + pemetrexed Edit

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Beijing, China, 100021
    • Not yet recruiting
    • Research Site
  • Beijing, China, 100142
    • Not yet recruiting
    • Research Site
  • Beijing, China, 100044
    • Recruiting
    • Research Site
  • Chengdu, China, 610041
    • Recruiting
    • Research Site
  • Chengdu, China, 610041
    • Not yet recruiting
    • Research Site
  • Chongqing, China, 400016
    • Not yet recruiting
    • Research Site
  • Fuzhou, China, 350001
    • Recruiting
    • Research Site
  • Fuzhou, China, 350005
    • Recruiting
    • Research Site
  • Guangzhou, China, 510080
    • Not yet recruiting
    • Research Site
  • Guangzhou, China, 510100
    • Withdrawn
    • Research Site
  • Guangzhou, China, 510289
    • Not yet recruiting
    • Research Site
  • Hangzhou, China, 310020
    • Recruiting
    • Research Site
  • Hefei, China, 230022
    • Not yet recruiting
    • Research Site
  • Hefei, China, 230031
    • Withdrawn
    • Research Site
  • Jinan, China, 250014
    • Recruiting
    • Research Site
  • Jinan, China, 250014
    • Withdrawn
    • Research Site
  • Kunming, China, 650118
    • Withdrawn
    • Research Site
  • Nanchang, China, 330006
    • Recruiting
    • Research Site
  • Nanchang, China, 330006
    • Not yet recruiting
    • Research Site
  • Nanjing, China, 210009
    • Recruiting
    • Research Site
  • Nanjing, China, 2100008
    • Withdrawn
    • Research Site
  • Ningbo, China, 315010
    • Recruiting
    • Research Site
  • Shanghai, China, 200030
    • Not yet recruiting
    • Research Site
  • Shanghai, China, 200433
    • Withdrawn
    • Research Site
  • Shanghai, China, 200120
    • Withdrawn
    • Research Site
  • Shenyang, China, 110042
    • Recruiting
    • Research Site
  • Shenyang, China, 110004
    • Not yet recruiting
    • Research Site
  • Tianjin, China, 300060
    • Recruiting
    • Research Site
  • Wuhan, China, 430022
    • Not yet recruiting
    • Research Site
  • Wuhan, China, 430030
    • Not yet recruiting
    • Research Site
  • Xi'an, China, 710004
    • Recruiting
    • Research Site
  • Xi'an, China, 710061
    • Withdrawn
    • Research Site
  • Zhengzhou, China, 450008
    • Recruiting
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for pre-screening:

1. Prior complete surgical resection (R0) and adjuvant osimertinib in EGFRm resectable SIB-IIIA NSCLC (AJCC 7th edition).
2. Off-treatment recurrence (including completed 3 years adjuvant osimertinib & discontinued adjuvant osimertinib before 3 years due to non-recurrence reason).
3. Newly diagnosed distant recurrent NSCLC (IVA or IVB) (per Version 9 of the International Association for the Study of Lung Cancer [IASLC] Staging Manual in Thoracic Oncology).
4. ≥6 months interval between recurrence and completion or discontinuation of adjuvant osimertinib.
5. Histologically/cytologically confirmed nonsquamous NSCLC (Investigators confirmed recurrence of primary lesion allowed if biopsy not available)
6. No prior systemic anti-cancer therapy after adjuvant therapy, but can receive local therapy (including surgery, radiotherapy, etc. per investigator choice).
7. Patients with asymptomatic or stable CNS metastases allowed.

Inclusion Criteria for screening:

1. Male or female, at least 18 years of age. Type of patient and disease characteristics
2. EGFR mutation (Exon 19del/Exon 21 L858R)-reconfirmed for study entry (mandatory undergo NGS by plasma, and tissue if applicable).
3. Life expectancy >12 weeks at Day 1.

Exclusion Criteria:

1. Patients with only local/regional recurrence.
2. Spinal cord compression and symptomatic brain metastases.
3. Past medical history of ILD, drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
4. Adjuvant osimertinib therapy was discontinued due to the occurrence of severe adverse events.
5. Prior with other adjuvant EGFR-TKIs (excluding osimertinib).
6. 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.
7. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
8. Contraindication for pemetrexed and cisplatin/carboplatin according to local approved label.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cohort1; Treatment allocation according to molecular profile at recurrence. Cohort 1 consists of patients with Ex19del or L858R mutation.

Drug: Osimertinib+cisplatin or carboplatin + pemetrexed Edit; Cohort 1 treated with osimertinib 80 mg once daily (QD) in combination with platinum-based chemotherapy cisplatin [75 mg/m2] or carboplatin [AUC5]) plus pemetrexed (500 mg/m2) on Day 1 every 3 weeks (Q3W) for 4 cycles, followed by osimertinib QD and pemetrexed Q3W till RECIST 1.1-defined progression or until another discontinuation criterion is met.; Other Names: Cohort1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the efficacy of osimertinib + chemotherapy by evaluation of PFS in patients who had distant recurrence after adjuvant osimertinib.	PFS is defined as the time from initiation of osimertinib combined with chemotherapy until progression per RECIST 1.1 as assessed by the investigator at local site, or death due to any cause. The analysis will include all patients who successfully enrolled in the study, satisfied all inclusion/exclusion criteria and have taken at least one dose of osimertinib plus chemotherapy. All events will be included, regardless of whether the patient withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. However, if the patient progresses or dies immediately after two or more consecutive missed visits, the patient will be censored at the time of the latest evaluable assessment prior to the two missed visits. The primary measure of interest is the median PFS.	Approximately 52 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	ORR is defined as the proportion of patients who have a confirmed CR or confirmed PR as determined by the investigator at local site per RECIST 1.1. The analysis will include all enrolled patients have taken at least one dose of osi plus chemotherapy. Data obtained from first dose up until progression, or the last evaluable assessment in the absence of progression will be included in the assessment of ORR, regardless of whether the patient withdraws from therapy. Patient who discontinues treatment without a response or progression, receive a subsequent therapy, and then respond will not be included as responder in the ORR.	Approximately 52 months
TTD	TTD is defined as time from first dose of osimertinib + chemotherapy until discontinuation of treatment for any reason, including disease progression, toxicity, and death. The analysis will include all patients who successfully enrolled in the study, satisfied all inclusion/exclusion criteria and have taken at least one dose of osimertinib plus chemotherapy. Median TTD will be described.	Approximately 52 months
depth of response	Depth of response (ie, tumour shrinkage/change in tumour size) by investigator assessment at local site was defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline.	Approximately 52 months
DCR	DCR is defined as the percentage of patients who have a confirmed CR/PR or who have SD for at least 6 weeks minus 1 week per RECIST 1.1 as assessed by local site after date of first dose.	Approximately 52 months
DoR	DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause. The primary measure of interest is the median DoR.	Approximately 52 months
OS	OS is defined as time from first dose of osimertinib and chemotherapy until the date of death due to any cause. Landmark rate at 36 months of OS will be described.	Approximately 52 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety and tolerability	Safety and tolerability will be evaluated in terms of AEs (graded by CTCAE v5), vital signs (pulse and blood pressure), clinical laboratory, physical examination, ECG parameters, LVEF, and ECOG Performance Status.	Approximately 52 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2026
• Primary Completion (Estimated): May 18, 2030
• Study Completion (Estimated): May 18, 2030

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Carcinoma, Non-Small-Cell Lung; Thoracic Neoplasms; Bronchial Neoplasms; osimertinib; Neoplasms by Site; Lung Neoplasms; Carcinoma, Bronchogenic; Respiratory Tract Neoplasms
• Additional Relevant MeSH Terms: Bronchial Diseases; Neoplasms; Lung Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Diseases; Thoracic Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Bronchial Neoplasms; Carcinoma, Bronchogenic; Organic Chemicals; Coordination Complexes; Carboplatin
• Other Study ID Numbers: D5164L00004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared
• IPD Sharing Time Frame: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No