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

NCT04695925 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: ESR-21-21647
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Non-small Cell Carcinoma; EGFR Gene Mutation

Outcome Measures

Primary Outcomes (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

  assessed up to 36 months

Secondary Outcomes (4)

• overall survival

  OS maturity reaches 60%, assessed up to 60 months

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

  up to 36 months

• Incidence and severity of adverse events (AEs)

  through study completion, an average of 60 months

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

  up to 36 weeks

Other Outcomes (1)

• Correlation between subtypes of EGFR mutations, TP53 mutations and other potential predictive biomarkers and response to treatment.

  up to 36 months

Study Arms (2)

osimertinib monotherapy

ACTIVE COMPARATOR

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

Drug: Osimertinib

combination of osimertinib and chemotherapy

EXPERIMENTAL

Osimertinib, 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.

Drug: Osimertinib; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Osimertinib DRUG

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

combination of osimertinib and chemotherapy; osimertinib monotherapy

Pemetrexed DRUG

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

combination of osimertinib and chemotherapy

Carboplatin DRUG

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

combination of osimertinib and chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Li Zhang, MD: lead
• Cancer Hospital of Guangxi Medical University: collaborator
• First People's Hospital of Foshan: collaborator
• Henan Cancer Hospital: collaborator

Study Sites (2)

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

Guangzhou, Guangdong, 510060, China

Location

Central Hospital of Guangdong Nongken, Zhanjiang Cancer Hospital

Zhanjiang, China

Location

MeSH Terms

Interventions

osimertinib; Pemetrexed; Carboplatin

Intervention Hierarchy (Ancestors)

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; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2020
• First Posted: January 5, 2021
• Study Start: March 29, 2021
• Primary Completion: November 1, 2025
• Study Completion (Estimated): December 30, 2027
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)