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OSIMERTINIB MESYLATE

Osimertinib mesylate is a targeted cancer medicine taken by mouth that is being studied in several clinical trials, mainly for non-small cell lung cancer (NSCLC) with specific EGFR gene mutations. These trials look at how well it works in different situations (first treatment, after surgery, and after resistance develops) and also test it in combinations with other anti-cancer drugs. This article explains what these studies are testing, what outcomes they measure, and what participation may involve.

Table of Contents

What is Osimertinib Mesylate?

Osimertinib mesylate is studied as an oral targeted therapy for non-small cell lung cancer (NSCLC), especially when the cancer has certain EGFR gene mutations.[1]

In the provided trial data, osimertinib is also referred to by names such as AZD9291 and the brand name TAGRISSO.[2][3][4]

Who is Being Studied in These Trials?

Many studies enroll people with EGFR mutation-positive NSCLC that is locally advanced (spread in the chest area) or metastatic (spread to other body parts).[1][5]

Some trials focus on cancer that returned or progressed after earlier treatments, including relapse after postoperative adjuvant targeted therapy or resistance after prior EGFR-targeted drugs.[6][7][8]

There are also trials that specifically include patients with additional resistance-related findings such as MET amplification or MET overexpression after EGFR-TKI resistance.[9][10]

One trial includes patients with EGFR exon 20 insertion mutations and studies a combination using a higher daily dose of osimertinib (160 mg).[11]

Some studies also involve people with brain metastases (cancer spread to the brain) and compare an osimertinib arm to other treatment strategies.[12]

Not all trials are in cancer patients: one study enrolls healthy volunteers to compare pharmacokinetics between a different drug (TY-9591) and osimertinib and to test food effects on TY-9591.[3]

How Osimertinib is Given in the Studies

Across multiple trials, osimertinib is given by mouth as a tablet once daily, commonly at 80 mg once daily (QD).[6][1][2][13]

In one phase II combination study for EGFR exon 20 insertion mutations, osimertinib is dosed at 160 mg once daily together with JMT101 infusion.[11]

Some trials describe treatment continuing until disease progression (the cancer grows), intolerable toxicity (side effects that are too severe), or other study stopping rules.[1][6]

One trial studying retreatment after relapse following surgery and adjuvant therapy allows treatment up to 3 years unless the disease progresses or other stopping criteria occur.[6]

Types of Clinical Trial Situations Being Tested

Osimertinib trials in this dataset cover several real-world treatment situations in NSCLC.[1][6][7]

  • First-line therapy: One phase II study evaluates osimertinib as initial treatment for EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC and explores whether different EGFR mutation subtypes respond differently.[1]

  • After surgery and adjuvant targeted therapy relapse: A phase II single-arm study tests osimertinib in patients with EGFR-sensitive mutation NSCLC whose disease progressed after radical surgery and postoperative adjuvant targeted therapy, asking whether EGFR-TKI “re-treatment” can work after relapse.[6]

  • After resistance to osimertinib or other EGFR TKIs: Multiple studies test combinations designed for patients whose disease has become resistant, including settings such as gradual progression on osimertinib and later-line treatment with additional molecular changes like MET amplification.[7][14][9]

  • Advanced solid tumors programs that include osimertinib combinations: Some studies include advanced solid tumors and evaluate combinations where osimertinib may be one of the partner drugs, with outcomes such as ORR and safety endpoints.[15][16]

What Outcomes Do These Trials Measure?

Trials measure whether treatment shrinks tumors, delays growth, and how safe the treatments are.[6][9][11]

  • Objective response rate (ORR): The percentage of patients whose tumors shrink enough to count as a complete response (CR) or partial response (PR), often measured by RECIST 1.1 criteria.[6][17]

  • Progression-free survival (PFS): How long it takes until the cancer objectively worsens or the patient dies (definitions vary slightly by trial and may be assessed by investigator or independent reviewers).[6][9][7]

  • Duration of response (DoR/DOR): How long a CR or PR lasts before the cancer progresses or death occurs, depending on the trial definition.[6][11]

  • Disease control rate (DCR): The percentage of patients who have CR, PR, or stable disease (SD).[6][17]

  • Overall survival (OS): Time from a starting point (such as randomization or first dose) until death from any cause.[6][5]

  • Depth of response (DepOR): How much the tumor shrinks at its smallest size compared with baseline measurements, assessed using RECIST target lesions in at least one trial.[6]

Some trials specify who assesses response: for example, by the investigator, by a Blinded Independent Review Committee (IRC), or by BICR in a randomized phase III trial design.[6][11][12]

Combination Approaches Being Studied

A major theme across these trials is pairing osimertinib with other drugs to improve results, especially when resistance develops.[2][7][9]

  • MET-pathway combinations: Some randomized and single-arm studies test osimertinib together with MET inhibitors (for example, glumetinib or savolitinib) in NSCLC with MET amplification/overexpression or low copy number MET amplification, aiming to address resistance.[9][10][14]

  • Anti-angiogenesis combination: One phase II trial studies osimertinib plus anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib, based on the idea that tumor blood-vessel pathways (VEGF/VEGFR) may contribute to resistance.[7]

  • Cell-death / apoptosis-related combination: A phase Ib study tests APG-1252 (given by IV infusion) together with osimertinib 80 mg daily and uses dose-escalation methods to determine safe dosing and then explores activity using RECIST 1.1 assessments.[2]

  • Investigational targeted combinations: Trials include ONO-7475 plus osimertinib (phase I) in first-line EGFR-mutated stage IIIB/IIIC/IV or recurrent NSCLC and measure safety outcomes like DLTs plus effectiveness outcomes such as ORR and PFS.[5]

  • Antibody-drug conjugate (ADC) combinations: Phase II studies evaluate BL-B01D1 (also listed as izalontamab brengitecan and BMS-986507) in combination with osimertinib 80 mg daily, measuring ORR, PFS, DCR, DOR, and treatment-emergent adverse events.[17][18]

  • EGFR exon 20 insertion strategy: A phase II study evaluates JMT101 (IV infusion every two weeks) plus osimertinib 160 mg daily in locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, using IRC-assessed ORR as the primary outcome.[11]

  • PI3K inhibitor combination: One multi-center study evaluates TQ-B3525 tablets combined with osimertinib in advanced NSCLC after EGFR inhibitor therapy failure and includes DLT and ORR as key outcomes.[8]

  • Aurora A inhibitor combination: A phase I trial evaluates VIC-1911 tablets combined with osimertinib tablets in advanced NSCLC, focusing on safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity endpoints such as DCR, PFS, and OS.[4]

Surgery-Related and Perioperative Study Approaches

Some trials connect targeted therapy (including osimertinib) with surgery timing in NSCLC.[13][19]

  • Downstaging then salvage surgery: In one prospective single-arm multi-center study, participants who have tumor downstaging (to stage IIIA or below) confirmed by PET-CT after targeted therapy may undergo salvage surgery (defined as lobectomy plus lymphadenectomy), and targeted therapy can continue after surgery until progression.[13]

  • Perioperative combination options: A randomized phase II perioperative study includes a group where SHR-A2102 is combined with other therapies, including a comparator group listing Osimertinib Mesylate among possible partner EGFR-TKIs, and measures outcomes like pathology complete response (pCR), event-free metrics, and safety.[19]

Pharmacokinetics (How the Body Handles the Drug) Studies

One randomized, open-label two-phase study in healthy volunteers compares pharmacokinetics (PK) of TY-9591 tablets versus Osimertinib Mesylate after a single fasting dose and then evaluates the effect of a high-fat meal on TY-9591 PK.[3]

This study measures PK values such as Cmax (peak blood level), Tmax (time to peak), and AUC (overall exposure) for osimertinib and its metabolites (AZ5104 and AZ7550), along with multiple other PK parameters and safety variables.[3]

Safety Monitoring in These Trials

Many trials track adverse events (AEs) (unwanted medical problems during treatment) and serious adverse events (SAEs) (more severe events such as those requiring hospitalization) as key outcomes.[6][15][12]

Early-phase combination studies often focus on dose-limiting toxicities (DLTs) to help determine a safe dose, and may also define maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) depending on the study.[5][2][8]

One EU clinical trial record for a phase 1/2a study lists key eligibility concepts such as having at least one measurable lesion by RECIST, ECOG performance status 0–1, and a life expectancy of at least 3 months, and it also lists several safety endpoints including counts of AEs, SAEs, DLTs, and AEs leading to discontinuation or death.[16]

Topic What the trials show (high-level)
Main disease studied Non-small cell lung cancer (NSCLC), especially EGFR mutation-positive disease (including sensitizing mutations and exon 20 insertions), plus resistance settings (e.g., after prior EGFR-TKI or osimertinib).
How osimertinib is given Most commonly oral tablets once daily, often 80 mg daily; one combination study uses 160 mg daily.
Study situations First-line treatment; treatment after relapse after surgery and adjuvant therapy; treatment after resistance; perioperative and advanced disease settings; and pharmacokinetic comparison in healthy volunteers.
Combination strategies Studied with multiple agents (e.g., MET inhibitors like glumetinib or savolitinib; anti-angiogenic anlotinib; and investigational agents like ONO-7475, APG-1252, VIC-1911, BL-B01D1, JMT101).
Common outcomes measured ORR, PFS, DoR, DCR, OS, depth of response; plus safety outcomes like AEs/SAEs and early-phase DLT/MTD/RP2D.
How response is measured Often by RECIST 1.1 on imaging (such as CT), sometimes with independent review (IRC/BICR).

FAQ

  • What type of cancer is osimertinib mesylate mainly being studied for in these trials? In the provided trials, osimertinib mesylate is mainly studied for non-small cell lung cancer (NSCLC), especially when the cancer has EGFR gene mutations (including sensitizing mutations, exon 20 insertion mutations, and situations where resistance develops after earlier EGFR-targeted therapy).
  • How is osimertinib usually taken in these studies? Most trials use osimertinib mesylate as an oral tablet taken once daily. Several studies use 80 mg once daily, and one study uses 160 mg once daily when combined with another drug.
  • Why do some trials combine osimertinib with other medicines? Some studies test combinations because the cancer can become resistant to EGFR-targeted drugs over time. Trials are exploring whether adding another medicine (such as MET inhibitors, anti-angiogenesis drugs, or other targeted agents) can improve tumor shrinkage or delay cancer growth.
  • What do researchers measure to decide if a treatment is working? Common measures include objective response rate (how many people have tumor shrinkage), progression-free survival (how long before the cancer grows or the patient dies), duration of response (how long tumor shrinkage lasts), disease control rate (shrinkage or stable disease), and overall survival.
  • Are there studies of osimertinib outside of cancer treatment settings? Yes. One trial in healthy volunteers compares how the body absorbs a different drug (TY-9591) versus osimertinib and also studies how food affects TY-9591 levels. Osimertinib is used there as a comparison drug for pharmacokinetics.

Ongoing Clinical Trials on OSIMERTINIB MESYLATE

  • Study on the Safety and Effects of BMS-986507 with Pembrolizumab and Osimertinib Mesylate in Adults with Advanced Solid Tumors

    Recruiting

    1 1 1
    Investigated drugs:
    France Italy The Netherlands Spain

Glossary

  • Osimertinib mesylate: A targeted cancer medicine given as a tablet by mouth. In these trials it is used for certain types of non-small cell lung cancer, often linked to EGFR gene mutations.
  • TAGRISSO: A brand name listed in the trial data for osimertinib tablets.
  • AZD9291: Another name used in the trial data for osimertinib (seen as an “other name” in some study descriptions).
  • Non-small cell lung cancer (NSCLC): The most common major group of lung cancers. Many of the trials here focus on NSCLC.
  • EGFR mutation (EGFR gene mutation): A change in the EGFR gene that can help drive cancer growth. Some lung cancers with EGFR mutations may respond to EGFR-targeted medicines like osimertinib.
  • EGFR sensitizing mutation / EGFR-sensitive mutation: An EGFR mutation subtype described in the trials as more likely to respond to EGFR-targeted treatment.
  • EGFR exon 20 insertion mutation: A specific EGFR mutation subtype. One trial studies osimertinib 160 mg daily together with JMT101 for NSCLC with this mutation.
  • T790M mutation: A specific EGFR mutation linked to resistance to earlier EGFR-targeted drugs. Some trials discuss patients who are T790M positive or negative after earlier treatments.
  • Acquired resistance: When cancer that initially responded to a treatment later learns to grow despite it. Multiple trials here study treatments after resistance to EGFR TKIs, including resistance to osimertinib.
  • MET amplification: An increase in the number of MET gene copies. Some trials focus on NSCLC where MET amplification (or overexpression) is linked to resistance, and test combinations such as osimertinib with MET inhibitors.
  • Low copy number MET amplification: In one trial, defined as MET copy number below 5 measured by NGS or FISH, used to select patients for osimertinib plus savolitinib.
  • MET overexpression: Higher-than-usual MET protein levels (described as a selection factor in some trials), which may be associated with resistance and is being targeted in combination strategies.
  • EGFR-TKI (EGFR tyrosine kinase inhibitor): A type of targeted therapy that blocks signals from EGFR. Osimertinib is described as a third-generation EGFR inhibitor in the trial data.
  • Third-generation EGFR-TKI: A later-generation EGFR-targeted drug class. Osimertinib is described this way in the trial information.
  • First-line treatment: The first main treatment given for a disease. Some trials study osimertinib as first-line therapy for advanced EGFR-mutated NSCLC.
  • Adjuvant targeted therapy: Treatment given after surgery to reduce the risk of cancer returning. One trial studies osimertinib after the cancer progresses following adjuvant targeted therapy after radical surgery.
  • Neoadjuvant therapy / Induction therapy: Treatment given before surgery to shrink the tumor. One trial uses targeted therapy (including osimertinib) before salvage surgery in advanced NSCLC after downstaging is confirmed.
  • Downstaging: When a cancer becomes a lower stage after treatment, often because it shrinks or spreads less. One study enrolls people whose disease downstages to stage IIIA or lower before surgery.
  • Salvage surgery: Surgery done after initial non-surgical treatment, for patients who originally could not have surgery but later become eligible (for example after tumor downstaging).
  • Lobectomy: Surgery to remove a lobe of the lung. Mentioned as part of standard salvage surgery in one trial.
  • Lymphadenectomy: Surgery to remove lymph nodes, often to check for spread of cancer. Mentioned in one trial’s salvage surgery definition.
  • RECIST 1.1: A standard set of rules used on scans (like CT) to measure tumors and classify response as complete response, partial response, stable disease, or progressive disease.
  • Objective response rate (ORR): The percentage of patients whose tumors shrink by a defined amount (complete response or partial response) using rules like RECIST 1.1.
  • Complete response (CR): A response category meaning all target tumors disappear on scans (as defined by RECIST in these trials).
  • Partial response (PR): A response category meaning tumors shrink by a defined amount (for example at least a 30% decrease in the sum of target lesion diameters in RECIST-based definitions used in these trials).
  • Stable disease (SD): A response category meaning the cancer is not shrinking enough to be PR, but also not growing enough to be progressive disease.
  • Progressive disease (PD): A response category meaning the cancer has grown enough to meet progression rules (for example RECIST-based growth or new lesions).
  • Progression-free survival (PFS): How long patients live without the cancer getting worse (or until death, depending on the trial definition). Many trials here use PFS as a main outcome.
  • Overall survival (OS): How long patients live, measured from a defined starting point such as randomization or first dose, until death from any cause.
  • Duration of response (DoR / DOR): How long a tumor response (CR or PR) lasts before the cancer grows again or the patient dies (depending on the trial definition).
  • Disease control rate (DCR): The percentage of patients who achieve CR, PR, or stable disease.
  • Depth of response (DepOR): How much the tumor shrinks at its smallest point (nadir) compared with baseline size, using RECIST target lesion measurements.
  • Dose-limiting toxicity (DLT): A side effect serious enough to prevent giving a higher dose. Several early-phase combination trials use DLTs to help choose a safe dose.
  • Maximum tolerated dose (MTD): The highest dose that can be given with acceptable side effects, often determined in early-phase trials (for example with a “3+3” dose-escalation design).
  • Recommended Phase 2 dose (RP2D): A dose chosen after early testing (based on safety and other data) to be used in later studies that focus more on effectiveness.
  • Recommended Phase II Dose (RP2D) for BL-B01D1: In BL-B01D1 combination trials, the sponsor selects a recommended dose for phase II based on safety, tolerability, and other data gathered earlier.
  • Pharmacokinetics (PK): How the body absorbs, distributes, breaks down, and removes a drug. Some trials measure PK values like Cmax, Tmax, AUC, and Ctrough.
  • Cmax: The highest (peak) drug level measured in blood after dosing.
  • Tmax: The time it takes to reach the peak drug level (Cmax) in blood.
  • AUC: “Area under the curve,” a measure of overall drug exposure in the blood over time.
  • Ctrough: The lowest drug level in the blood just before the next dose.
  • Anti-drug antibody (ADA): Antibodies the body might make against a drug (often biologic drugs). Some trials measure ADA frequency to understand immune reactions.
  • Immunogenicity: How likely a drug is to trigger an immune response (like forming anti-drug antibodies). One combination trial measures this for JMT101.
  • Blinded Independent Review Committee (IRC): A group that reviews scan results independently (and “blinded,” meaning not told which treatment a patient received) to reduce bias when judging tumor response.
  • Open-label: A study design where participants and researchers know which treatment is being given.
  • Single-arm study: A study where all participants receive the same treatment (no comparison group). Several osimertinib studies here are single-arm.
  • Randomized controlled trial: A study where participants are assigned by chance to different groups, such as a combination treatment versus standard chemotherapy or another targeted drug.
  • Brain metastases: Cancer that has spread to the brain. One phase III trial compares another treatment plus chemotherapy versus osimertinib in NSCLC patients with brain metastases.
  • ECOG performance status: A scale describing how well a person can carry out daily activities. One trial lists eligibility as ECOG 0 or 1 (fully active or restricted in strenuous activity but able to do light work).
  • Measurable lesion: A tumor spot that can be measured on imaging scans using RECIST rules, used to track response to treatment.
  • PET-CT: A scan combining PET (metabolic activity) and CT (detailed anatomy). One trial uses PET-CT to confirm downstaging before salvage surgery.
  • Platinum-based doublet chemotherapy: A common chemotherapy approach using a platinum drug (cisplatin or carboplatin) plus another drug (like pemetrexed). One phase III trial uses this as a comparison group.
  • Anti-angiogenic agent: A drug that targets blood vessel growth that tumors use to get nutrients. One trial studies osimertinib combined with anlotinib, described as targeting pathways involved in tumor angiogenesis.

References

  1. https://clinicaltrials.gov/study/NCT03460275
  2. https://clinicaltrials.gov/study/NCT04001777
  3. https://clinicaltrials.gov/study/NCT04798638
  4. https://clinicaltrials.gov/study/NCT05489731
  5. https://clinicaltrials.gov/study/NCT06525246
  6. https://clinicaltrials.gov/study/NCT06530719
  7. https://clinicaltrials.gov/study/NCT04438902
  8. https://clinicaltrials.gov/study/NCT05284994
  9. https://clinicaltrials.gov/study/NCT06829459
  10. https://clinicaltrials.gov/study/NCT06908772
  11. https://clinicaltrials.gov/study/NCT05132777
  12. https://clinicaltrials.gov/study/NCT06970639
  13. https://clinicaltrials.gov/study/NCT05085054
  14. https://clinicaltrials.gov/study/NCT07322783
  15. https://clinicaltrials.gov/study/NCT06895928
  16. https://clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-bms-986507-with-pembrolizumab-and-osimertinib-mesylate-in-adults-with-advanced-solid-tumors/
  17. https://clinicaltrials.gov/study/NCT06498986
  18. https://clinicaltrials.gov/study/NCT05880706
  19. https://clinicaltrials.gov/study/NCT07229729