In short
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.
Key points
- Clinical trials are studying osimertinib mesylate mostly in EGFR-mutated non-small cell lung cancer, including first-line use, treatment after relapse following surgery and adjuvant therapy, and treatment after resistance to earlier EGFR-targeted medicines. In many studies, osimertinib is taken as a tablet once daily, most often at 80 mg, and sometimes at higher doses in combinations. Researchers commonly measure tumor shrinkage (ORR), how long the cancer stays controlled (PFS, DoR, DCR), and survival (OS). Several trials test osimertinib together with other drugs (such as MET inhibitors or anti-angiogenesis drugs) to try to improve results when resistance develops. Safety is closely tracked through adverse events and, in early-phase studies, dose-limiting toxicities to help select safe doses.
At a glance
- 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).
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.
In the provided trial data, osimertinib is also referred to by names such as AZD9291 and the brand name TAGRISSO.
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).
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.
There are also trials that specifically include patients with additional resistance-related findings such as MET amplification or MET overexpression after EGFR-TKI resistance.
One trial includes patients with EGFR exon 20 insertion mutations and studies a combination using a higher daily dose of osimertinib (160 mg).
Some studies also involve people with brain metastases (cancer spread to the brain) and compare an osimertinib arm to other treatment strategies.
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.
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).
In one phase II combination study for EGFR exon 20 insertion mutations, osimertinib is dosed at 160 mg once daily together with JMT101 infusion.
Some trials describe treatment continuing until disease progression (the cancer grows), intolerable toxicity (side effects that are too severe), or other study stopping rules.
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.
Types of Clinical Trial Situations Being Tested
Osimertinib trials in this dataset cover several real-world treatment situations in NSCLC.
- 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.
- 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.
- 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.
- 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.
What Outcomes Do These Trials Measure?
Trials measure whether treatment shrinks tumors, delays growth, and how safe the treatments are.
- 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.
- 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).
- Duration of response (DoR/DOR): How long a CR or PR lasts before the cancer progresses or death occurs, depending on the trial definition.
- Disease control rate (DCR): The percentage of patients who have CR, PR, or stable disease (SD).
- Overall survival (OS): Time from a starting point (such as randomization or first dose) until death from any cause.
- 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.
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.
Combination Approaches Being Studied
A major theme across these trials is pairing osimertinib with other drugs to improve results, especially when resistance develops.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Surgery-Related and Perioperative Study Approaches
Some trials connect targeted therapy (including osimertinib) with surgery timing in NSCLC.
- 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.
- 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.
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.
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.
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.
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.
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.