Testing ATRA with tislelizumab in lung cancer that stopped responding to EGFR treatment
Tests safety of ATRA with tislelizumab in adults with EGFR-mutant lung cancer.
Plain-language title generated from the registry record
Registry title: Phase 1 Study of ATRA Plus a PD-1 Inhibitor in EGFR-Mutant NSCLC After Third-Generation EGFR-TKI Resistance
Key facts
- Where
- Beijing, ChinaSee the site
- Phase
- Phase 1
AI summary: who the study is looking for
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with EGFR-mutant non-small cell lung cancer that has worsened after a third-generation EGFR tyrosine kinase inhibitor and at least one standard treatment, or who cannot have standard treatment.
- Age
- 18 years or older.
- Sex
- Men and women can join.
- Disease stage
- Non-small cell lung cancer, stage IV or recurrent or metastatic, that cannot be treated with local treatment meant to remove all of the disease. At least one measurable lesion is needed.
- Earlier treatment
- Must have had a third-generation EGFR tyrosine kinase inhibitor (such as osimertinib, almonertinib or furmonertinib), with scan-confirmed worsening. Must also have had at least one standard systemic treatment after that, or be unable to take standard treatment.
- Biomarker or test result
- A confirmed sensitizing EGFR mutation, such as an exon 19 deletion or an exon 21 L858R mutation.
Main reasons for not taking part
- Another cancer in the past, unless it is clinically removed with a low risk of coming back
- Uncontrolled brain or leptomeningeal metastases
- Change of the cancer into small cell lung cancer
- Active infection, active tuberculosis, HIV-positive, or active hepatitis B or C
- Pregnant or breastfeeding
Read by machine on 12 November 2026.
Where in China
- National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalBeijing, ChinaContact: National Cancer Center National Clinical Research CenterNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorTrial details
- Who runs it
- Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Trial code
- NCT07842887
- Record updated
- 25 September 2026
- Original description
The goal of this Phase 1 clinical trial is to learn whether all-trans retinoic acid (ATRA) combined with tislelizumab is safe and tolerable in adults with EGFR-mutant non-small cell lung cancer (NSCLC). The study is for people whose cancer has worsened after treatment with a third-generation EGFR tyrosine kinase inhibitor and at least one standard systemic treatment, or who cannot tolerate or are not suitable for currently available standard treatments.Read full original descriptionShow less
A Phase 1 Clinical Study of All-Trans Retinoic Acid in Combination With a PD-1 Inhibitor in Patients With EGFR-Mutant Non-Small Cell Lung Cancer After Acquired Resistance to a Third-Generation EGFR Tyrosine Kinase Inhibitor
The goal of this Phase 1 clinical trial is to learn whether all-trans retinoic acid (ATRA) combined with tislelizumab is safe and tolerable in adults with EGFR-mutant non-small cell lung cancer (NSCLC). The study is for people whose cancer has worsened after treatment with a third-generation EGFR tyrosine kinase inhibitor and at least one standard systemic treatment, or who cannot tolerate or are not suitable for currently available standard treatments.
The main questions this study aims to answer are:
* What side effects and dose-limiting toxicities occur with the combination of ATRA and tislelizumab? * What is the highest dose of ATRA that can be given safely with tislelizumab, and what dose should be recommended for future studies?
Researchers will also look for early signs that the combination can shrink or control the cancer and will assess how long participants live without their cancer getting worse and how long they live overall. Tumor tissue and blood samples will be studied to explore changes in the cancer and the immune system and to identify possible markers associated with treatment response or side effects.
All participants will receive ATRA and tislelizumab; there is no comparison or placebo group. Participants will:
* Take ATRA by mouth twice daily, beginning 7 days before the first dose of tislelizumab. The ATRA dose will be assigned according to the dose level being studied. * Receive tislelizumab by intravenous infusion once every 3 weeks. * Undergo regular safety assessments, including physical examinations, blood tests, vital-sign measurements, and monitoring for side effects. * Undergo imaging examinations approximately every 6 weeks during the first year to assess the cancer. * Provide tumor tissue and blood samples for biomarker research. * Attend an end-of-treatment visit, safety follow-up visits, and survival follow-up approximately every 3 months after treatment ends.
Inclusion: Voluntarily provides written informed consent and agrees to comply with the study requirements; Aged 18 years or older, with no restriction based on sex; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants with an ECOG performance status of 2 may be enrolled at the investigator's discretion; Histologically or pathologically confirmed primary non-small cell lung cancer (NSCLC); Stage IV disease according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system, or recurrent or metastatic NSCLC that is not suitable for curative local treatment; A confirmed sensitizing EGFR mutation, including but not limited to an exon 19 deletion or an exon 21 L858R mutation; Previous treatment with a third-generation EGFR tyrosine kinase inhibitor, including but not limited to osimertinib, almonertinib, or furmonertinib, followed by radiographically confirmed disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1); Disease progression after at least one standard systemic treatment following resistance to a third-generation EGFR tyrosine kinase inhibitor, or inability to tolerate or unsuitability for currently available standard treatment, as determined by the investigator; No clearly available and appropriate standard targeted therapy option, as determined by the investigator; At least one measurable lesion according to RECIST v1.1; Adequate major organ function to receive the study treatment, as determined by the investigator; Female participants of childbearing potential must have a negative pregnancy test and agree to use effective contraception during study treatment and for at least 1 month after the last dose of all-trans retinoic acid; Able to understand and comply with the study requirements, as determined by the investigator.
Exclusion: A history of a Grade 3 or higher immune-related adverse event following treatment with an immune checkpoint inhibitor, or permanent discontinuation of immunotherapy because of immune-related toxicity; An unstable thrombotic or bleeding event requiring therapeutic intervention within 6 months before screening; Previous or current benign intracranial hypertension or pseudotumor cerebri; Current treatment with a tetracycline that cannot be discontinued; Current treatment with another anticancer therapy or investigational product without completion of the protocol-required washout period; History of another malignancy, except for a malignancy that has been clinically cured and is considered by the investigator to have a low risk of recurrence; Histologic transformation, such as transformation to small cell lung cancer; Uncontrolled acute or chronic infection, or an active infection requiring systemic anti-infective treatment; Active tuberculosis; Positive human immunodeficiency virus antibody test, active hepatitis B, or active hepatitis C; Active autoimmune disease, or a history of autoimmune disease requiring systemic immunosuppressive treatment; Severe or uncontrolled cardiovascular or cerebrovascular disease; Uncontrolled Grade 2 or higher hepatic dysfunction, or underlying liver disease that may substantially increase the risk of ATRA-related hepatotoxicity, as determined by the investigator; History of a severe hypersensitivity reaction to all-trans retinoic acid, another retinoid, tislelizumab, or any component of these products; Any other condition that, in the investigator's opinion, makes the individual unsuitable for participation in the clinical trial; Uncontrolled brain metastases, leptomeningeal metastases, or a central nervous system lesion requiring urgent local treatment; Clinically significant uncontrolled hyperlipidemia, particularly markedly elevated triglycerides, that may increase the risks associated with all-trans retinoic acid treatment, as determined by the investigator; Pregnant or breastfeeding, or planning pregnancy or conception during the study.