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Non-small Cell CarcinomaPhase 3TOPNCT04695925

Osimertinib Monotherapy or Combination With Chemotherapy for Advanced NSCLC Concurrent EGFR and TP53 Mutations

A Phase 3 study testing Osimertinib, Pemetrexed and Carboplatin in people with Non-small Cell Carcinoma and EGFR Gene Mutation, run by Li Zhang, MD at 2 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a phase III randomized trial in patients with advanced non-squamous NSCLC harboring EGFR-sensitizing mutations and concurrent TP53 mutations with a performance status of 0 to1 who are planned to receive first-line therapy. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Carcinoma, EGFR Gene Mutation
What is being tested?
Osimertinib, Pemetrexed and Carboplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
294 participants
Where
2 sitesChina
Study dates
29 Mar 2021to 30 Dec 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Provision of informed consent prior to any study specific procedures;
  • Male or female, aged at least 18 years;
  • Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
  • Life expectancy of at least 3 months;
  • Histologically or cytologically confirmed stage IV or recurrent non-squamous non-small cell lung carcinoma with activating EGFR mutations (exon 19 deletion or exon 21 L858R point mutation) and concurrent TP53 mutations;
  • No prior palliative chemotherapy, or palliative biological (including targeted therapies such as EGFR and vascular epidermal growth factor (VGEF) inhibitors) or immunological therapy （Previous adjuvant chemotherapy is permitted if treatment was completed more than 6 months before day 1. Palliative radiotherapy to a metastatic site is permitted, but palliative wide field radiotherapy to the lung must be completed at least 4 weeks before day 1 with no persistence of any radiotherapy-related toxicity;
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  • Adequate organ function, including the following:
  • Adequate bone marrow reserve: absolute neutrophil (segmented and bands) counts (ANC) ≥ 1.5X109/L, Platelets ≥100X109/L, HGB ≥90g/L. The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted;
  • Tumour Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (x ULN) if no liver metastases or ≤ 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases; alanine aminotransferase (ALT) \& aspartate aminotransferase (AST) ≤ 2.5 x ULN if no demonstrable liver metastases or AST\&ALT ≤ 5 x ULN in the presence of liver metastases;
  • Serum Creatinine ≤ 1.5 times the ULN and Creatinine Clearance ≥ 50 ml/min.
  • Females must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening
  • Post-menopausal defined as aged 50 years or more and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
  • Women under 50 years old would be consider postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
  • Subjects should not enter the study if any of the following exclusion criteria are fulfilled:
  • Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site);
  • Previous randomization in the present study or previous treatment with Osimertinib;
  • Known severe hypersensitivity to Osimertinib or any of the excipients of this product;
  • Known severe hypersensitivity to carboplatin, pemetrexed or any of the excipients of these products;
  • Known severe hypersensitivity to pre-medications required for treatment with carboplatin/ pemetrexed doublet chemotherapy;
  • History or presence of any other malignancy with the exception of basal cell carcinoma or cervical cancer in situ;
  • Past medical history of interstitial lung disease, drug induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease;
  • Any unresolved chronic toxicity ≥ CTCAE grade 2 from previous anticancer therapy;
  • As judged by the investigator, any evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease);
  • Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study;
  • Pregnancy or breast feeding;
  • Use of unapproved drugs or research drugs within 30 days before the start of the study;
  • Symptomatic brain metastases.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived QTc value;
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block;
  • Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, electrolyte abnormalities (including: Serum/plasma potassium < LLN; Serum/plasma magnesium < LLN; Serum/plasma calcium < LLN), congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes;
  • Correction of electrolyte abnormalities to within normal ranges can be performed during screening;
  • Pre-existing idiopathic pulmonary fibrosis evidence by CT scan at baseline;
  • Unable to tolerate carboplatin/pemetrexed doublet chemotherapy, as judged by the investigator;
  • Life expectancy of ≤ 12 weeks;
  • 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 (e.g. patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled HBV infection;
  • Screening for chronic conditions is not required. Should participants with HBV infection be included, patients are only eligible if they meet all the following criteria:
  • Demonstrated absence of HCV co-infection or history of HCV co-infection;
  • Demonstrated absence of HIV infection;
  • Participants 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 infection HBV are eligible if they are:
  • Negative for HBsAg and positive for hepatitis B core antibody [anti-HBc IgG]. In addition, patients must be receiving anti-viral prophylaxis for 2-4 weeks prior to study treatment and 6-12 months (TBD by hepatologist) post 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 and 6-12 months (TBD by hepatologist) post treatment.

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Department of Medical Oncology,Cancer Center of Sun Yat-Sen University

    Guangzhou, Guangdong, 510060

  • Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital

    Zhanjiang

Other trials in China

About this study

Official title: A Phase III, Multicentre, Randomized Controlled Study Comparing Osimertinib Monotherapy to Combination Therapy With Osimertinib, Carboplatin and Pemetrexed for Untreated Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer With Concurrent EGFR and TP53 Mutations(TOP)

This is a phase III randomized trial in patients with advanced non-squamous NSCLC harboring EGFR-sensitizing mutations and concurrent TP53 mutations with a performance status of 0 to1 who are planned to receive first-line therapy.

Read the detailed description

This is a multicenter, randomized, open label, phase III study comparing the progression free survival, overall survival, response rate, toxicity, quality of life between Osimertinib monotherapy and combination of osimertinib, pemetrexed, carboplatin in first-line treatment of advanced non-small cell lung cancer patients with concurrent EGFR and TP53 mutation. Besides, the association between other genetic mutations and efficacy will also be analyzed as exploratory endpoint. Eligible patients will be randomized to receive either osimertinib or osimertinib combined with pemetrexed and carboplatin in a 1:1 ratio.

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OsimertinibDrug

    Osimertinib, 80mg, QD, p.o. until disease progression

  • PemetrexedDrug

    pemetrexed 500 mg/m2 intravenously every 3 weeks until disease progression

  • CarboplatinDrug

    carboplatin area under curve 5 intravenously every 3 weeks for four cycles

Study groups in NCT04695925
Study groupRoleWhat they receive
osimertinib monotherapyActive comparatorOsimertinib, 80mg, QD, p.o. until disease progression
Receives: Drug: Osimertinib
combination of osimertinib and chemotherapyExperimentalOsimertinib, 80mg, QD, p.o. Pemetrexed 500 mg/m2 and carboplatin area under curve 5 intravenously every 3 weeks for four cycles, followed by maintenance pemetrexed.
Receives: Drug: Osimertinib; Drug: Pemetrexed; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression free survival

    defined as the time from randomization to the date of first documentation of from date of randomization until the date of first documented progression or date of death from any cause, whichever came first

    Measured: assessed up to 36 months

Secondary outcomes (4)

  1. overall survival

    from date of randomization until the date of death from any cause

    Measured: OS maturity reaches 60%, assessed up to 60 months

  2. percentage of participants with objective response (partial response [PR] plus complete response [CR])

    assessed using RECIST v.1.1

    Measured: up to 36 months

  3. Incidence and severity of adverse events (AEs)

    Overall incidence of AEs; the incidence of grade 3 or above AEs; the incidence of severe adverse events (SAE); the incidence of drug-related AEs; the incidence of AEs resulting in permanent withdrawal of drugs; the incidence of AEs leading to dose adjustment

    Measured: through study completion, an average of 60 months

  4. Change from baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Score.

    The EORTC QLQ-C30 consists of 30 questions that comprise aspects of participant's functioning assessment (physical, emotional, role, cognitive, and social); symptom scales (fatigue; nausea, vomiting, and pain; the global health/quality of life [QoL]); and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhoea, and financial difficulties), within a recall period of "the past week." Most questions used a 4-point scale (1=Not at all to 4=Very much; two questions used a 7-point scale (1=Very poor to 7=Excellent). Scores were averaged and transformed to a 0-100 scale; a higher score for Global Qol/functional scales=better level of functioning; a higher score for symptom scale=greater degree of symptoms.

    Measured: up to 36 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jan 2021
  2. Study start29 Mar 2021
  3. Primary completion1 Nov 2025 (estimated)
  4. Study completion30 Dec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
294 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04695925
Sponsor's protocol ID
ESR-21-21647
Acronym
TOP
Status last verified
Oct 2025
First submitted
20 Dec 2020
Last updated
15 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhou T, Zhou H, Gao F, Feng W, Jiang W, Huang L, Zhao F, Chen L, Ji M, Zhu J, Fang Y, Chen P, Wang P, Wu J, Zhuang L, Liu X, Deng M, Weng G, Li J, Yang C, Zhao H, Yang Y, Zhang L. Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial. JAMA. 2026 Aug 10. doi: 10.1001/jama.2026.10599. Online ahead of print.

    PubMed 42574006

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Osimertinib, Pemetrexed and Carboplatin in people with Non-small Cell Carcinoma and EGFR Gene Mutation, run by Li Zhang, MD at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 43 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression free survival (time frame: assessed up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04695925, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2025.

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