Osimertinib Clinical Trials

What Is Osimertinib?

Osimertinib is an FDA-approved medication for non-small cell lung cancer (NSCLC) patients with EGFR mutation. It is a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Osimertinib works by targeting specific mutations in the EGFR gene, which can drive the growth of cancer cells. By inhibiting this protein, the drug aims to slow or stop cancer progression.

Beyond its approved use, Osimertinib is being investigated in numerous clinical trials for various forms of lung cancer, including advanced and metastatic stages, and in combination with other therapies. These studies aim to assess its safety and effectiveness, as well as to understand its role in different treatment strategies for lung cancer.

Uses and Conditions Under Study

Osimertinib is extensively studied for various forms of non-small cell lung cancer (NSCLC), which is a common type of lung cancer where abnormal cells grow out of control. As an EGFR-TKI, it targets specific genetic mutations often found in NSCLC, aiming to inhibit cancer cell growth. A significant number of trials, totaling 120 trials, are investigating osimertinib for NSCLC under various names like Non-small Cell Lung Cancer, Non-Small Cell Lung Cancer, Non Small Cell Lung Cancer, NSCLC, Carcinoma, Non-Small-Cell Lung, and Metastatic Lung Non-Small Cell Carcinoma.

Beyond NSCLC, osimertinib is also being explored for broader lung cancer indications. These studies aim to understand its effectiveness across different types of lung cancer. There are 16 trials focused on general Lung Cancer.

The drug is also under investigation for specific stages of lung cancer, such as Stage IV Lung Cancer AJCC v8 (14 trials) and Stage IVA Lung Cancer AJCC v8 (8 trials), which represent advanced forms of the disease. Additionally, 14 trials specifically target tumors with EGFR Gene Mutation, leveraging osimertinib's mechanism of action to block the activity of this mutated protein.

Overall, there are 246 trials involving osimertinib, with 63 currently recruiting participants and 49 having been completed, enrolling a total of 65,327 participants since the first trial began in 2014.

Dosing

Osimertinib is primarily available as oral tablets. The most commonly studied strength is 80 mg, typically taken once daily (QD). This dose has been investigated both as a monotherapy and in combination with other treatments for non-small cell lung cancer (NSCLC), particularly in patients with EGFR mutations.

For example, trials have explored osimertinib 80 mg once daily in combination with platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed) on Day 1 every 3 weeks for 4 cycles, followed by continued osimertinib QD and pemetrexed. Other studies combine osimertinib 80 mg once daily continuously with capivasertib (320/400 mg twice daily from day 1 to 4 of a 7-day cycle) in 28-day cycles. Investigational approaches also include combining osimertinib with the ABCG2 inhibitor febuxostat to study its effects on cerebrospinal fluid concentrations.

Side Effects

In clinical trials, patients taking Osimertinib experienced various side effects. The most common side effect reported was infusion-related reaction, affecting 62.0% of patients taking Osimertinib, compared to 0.0% on placebo in one trial involving 421 patients. Other frequently observed side effects included:

• Paronychia (nail inflammation), which occurred in 51.7% of patients on Osimertinib compared to 29.6% on placebo across five trials (861 patients).
• Rash, reported by 40.0% of patients taking Osimertinib versus 29.4% on placebo in five trials (861 patients).
• Increased alanine aminotransferase (a liver enzyme), seen in 36.1% of Osimertinib patients compared to 15.9% on placebo in one trial (421 patients).
• Hypoalbuminaemia (low albumin levels in the blood), affecting 33.1% of patients on Osimertinib versus 6.2% on placebo in three trials (670 patients).
• Stomatitis (mouth inflammation), experienced by 28.3% of Osimertinib patients compared to 21.6% on placebo across five trials (861 patients).
• Constipation, reported in 24.9% of patients taking Osimertinib versus 14.4% on placebo in four trials (718 patients).
• Nausea, occurring in 24.4% of Osimertinib patients compared to 17.8% on placebo in four trials (718 patients).

Clinical Trial Results

Clinical trials have evaluated the effectiveness of Osimertinib in treating non-small cell lung cancer (NSCLC).

Treatment for Locally Advanced or Metastatic NSCLC

In a study (NCT02151981) comparing Osimertinib 80mg to platinum-based doublet chemotherapy in patients with locally advanced or metastatic NSCLC, Osimertinib showed significant improvements across several key measures:

• The Objective Response Rate (ORR), which measures tumor shrinkage or disappearance, was 70.6% for patients on Osimertinib, compared to 31.4% for those on chemotherapy.
• Patients treated with Osimertinib had a median Progression-Free Survival (PFS) of 10.1 months, meaning they lived for this duration without their cancer worsening, compared to 4.4 months for patients on chemotherapy.
• The median Duration of Response (DoR) was 9.7 months for Osimertinib, versus 4.1 months for chemotherapy.
• The median Overall Survival (OS) was 26.8 months for Osimertinib, compared to 22.5 months for chemotherapy.
• Tumors shrank by an average of 46.1% in patients receiving Osimertinib, versus 24.4% in those receiving chemotherapy.

Osimertinib in Specific Patient Populations

Another study (NCT02759835) investigated Osimertinib in patients with EGFR-mutated NSCLC, including those who had progressed on prior treatments. For patients whose cancer had progressed on prior 1st or 2nd generation EGFR TKI therapy and acquired a T790M mutation, the Objective Response Rate with Osimertinib was 66.7%, and the Disease Control Rate was 100%. In patients who had not received prior TKI therapy (TKI-naïve), Osimertinib achieved an Objective Response Rate of 70.8% and a Disease Control Rate of 100%. The median Progression-Free Survival for all participants who started Osimertinib on trial was 14.7 months for those with prior 1st/2nd generation TKI progression and a T790M mutation (Cohort 1), and 11.0 months for those who had progressed on Osimertinib itself (Cohort 2). Median Overall Survival was 38.2 months for Cohort 1 and 33.7 months for Cohort 2.

Osimertinib in Combination Therapy

In a study (NCT02789345) combining Osimertinib with ramucirumab, the Objective Response Rate was 76%, with a Disease Control Rate of 92%. Median Progression-Free Survival was 11.04 months, and the median Duration of Response was 13.37 months.

Currently Recruiting Trials

Researchers are actively investigating new ways to use osimertinib, both alone and in combination with other therapies, for patients with non-small cell lung cancer (NSCLC). These studies aim to improve treatment outcomes, explore new patient populations, and understand how to overcome resistance to existing treatments. Here are some of the trials currently seeking participants:

• An observational study, NCT07363252, is investigating the mechanisms of recurrence in EGFR-mutated NSCLC patients who have received adjuvant osimertinib after surgery. This study is open to 100 participants.
• For patients with advanced EGFR-mutated NSCLC, a Phase 1/2 study, NCT07535437, is evaluating the safety and effectiveness of ivonescimab when combined with either Dato-DXd or osimertinib. This trial plans to enroll 66 individuals.
• AstraZeneca is sponsoring a Phase 2 study, NCT07295821, to assess osimertinib as an induction therapy before radiotherapy and as maintenance treatment for chemotherapy-ineligible or refusing adult patients with Stage III unresectable EGFR-mutated NSCLC. The target enrollment for this study is 60 patients.
• Another Phase 2 study, NCT07329322, is exploring sacituzumab tirumotecan in combination with osimertinib, or as a monotherapy, for neoadjuvant treatment in patients with resectable EGFR-mutated NSCLC. This trial aims to include 60 participants.
• The Jonsson Comprehensive Cancer Center is conducting a Phase 2 trial, NCT07323641, to test telisotuzumab vedotin and osimertinib for progressive, incurable non-small cell lung cancer. This study is designed for 60 patients.
• A large Phase 2/3 study, NCT07005102, sponsored by AbbVie, is assessing the safety and disease activity of intravenous telisotuzumab adizutecan in combination with osimertinib as a first-line treatment for locally advanced unresectable or metastatic EGFR-mutated non-squamous NSCLC. This trial has a target enrollment of 854 participants.
• In a Phase 3 study, NCT06838273, BL-B01D1 in combination with osimertinib is being compared to osimertinib alone as a first-line treatment for patients with EGFR-mutated locally advanced or metastatic NSCLC. This trial seeks to enroll 720 patients.
• AstraZeneca is also sponsoring a Phase 3 study, NCT06417814, to investigate Dato-DXd with or without osimertinib compared to platinum-based doublet chemotherapy in patients with EGFR-mutated locally advanced or metastatic NSCLC. This study plans to enroll 744 participants.
• For patients with NSCLC that has spread to the brain, a Phase 2 study, NCT06741085, is comparing stereotactic radiosurgery (SRS) after 3 months of osimertinib therapy versus osimertinib alone. This trial aims for 56 participants.
• Shanghai JMT-Bio Inc. is conducting a Phase 3 study, NCT06829459, to evaluate glumetinib combined with osimertinib mesylate versus platinum-based doublet chemotherapy in NSCLC patients who have developed resistance to EGFR-TKIs. This study plans to enroll 350 patients.

Where to Participate

Clinical trials involving osimertinib are conducted across a wide geographical area, offering opportunities for participation in many locations. The research network spans 51 states, with studies taking place in 744 cities and 1253 sites.

The top cities with the most recruiting sites include:

• St Louis, Missouri (23 sites)
• Honolulu, Hawaii (23 sites)
• Seattle, Washington (21 sites)
• New York, New York (20 sites)
• Milwaukee, Wisconsin (19 sites)
• Des Moines, Iowa (18 sites)
• Anchorage, Alaska (17 sites)
• Houston, Texas (17 sites)
• Chicago, Illinois (16 sites)
• Dayton, Ohio (16 sites)

Most studies are open to adults aged 18-130 years, regardless of gender. However, healthy volunteers are typically not eligible, and children are generally excluded from these trials.

Development Timeline

The journey of osimertinib in clinical research began on March 28, 2014, with the latest trial starting on April 17, 2026. Initially, research explored conditions such as IBS-C and hyperphosphatemia, but the focus quickly shifted and significantly expanded to non-small cell lung cancer (NSCLC), which became the primary area of investigation.

Since its inception, a total of 246 trials have been conducted or are ongoing, enrolling over 65,327 participants. The development pipeline has progressed through various stages, with the majority of studies being Phase 2 (107 trials) and Phase 1 (45 trials), indicating a strong emphasis on exploring new applications and combinations. There are also a significant number of Phase 3 trials (32), which are typically large-scale studies designed to confirm efficacy and safety before regulatory approval.

AstraZeneca has been a leading sponsor, driving 29 of these trials. Other key contributors to osimertinib's development include the National Cancer Institute (NCI) and Memorial Sloan Kettering Cancer Center, among many others. The range of conditions studied has broadened considerably within NSCLC, encompassing various stages (Stage I to IV), specific EGFR mutations (like exon 19 deletion, L858R, and T790M), and addressing challenges such as brain metastases and resistance mechanisms. This extensive research reflects a continuous effort to optimize osimertinib's role in treating lung cancer.