Locally Advanced or Metastatic NSCLC
Conditions
Keywords
NSCLC, Osimertinib, EGFR exon 20 insertion mutation
Brief summary
This is a single-arm, non-randomized multicentre phase 2 study in NSCLC patients with EGFR exon 20 insertion mutation, whose disease has progressed on standard chemotherapy.
Detailed description
EGFR exon 20 insertion-mutant NSCLCs are generally resistant to 1st-generation EGFR tyrosine kinase inhibitors (TKIs) as well as 2nd-generation EGFR TKIs (overall response rates of 0-8.7%). Osimertinib is an oral, potent, irreversible EGFR-TKI selective for sensitizing EGFR and EGFR T790M resistance mutations with a significant selectivity margin against wild-type EGFR. Osimertinib is potent with a wide therapeutic window in Ba/F3 cells with EGFR exon 20 insertion mutations. Therefore, this study will be performed to investigate the efficacy of osimertinib in NSCLC patients with EGFR exon 20 insertion mutation
Interventions
DRUGOsimertinib 80 MG [Tagrisso]
Osimertinib 80mg once daily until disease progression
Sponsors
AstraZeneca
Korean Cancer Study Group
Seoul National University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedures 2. Male or female must be \> 19 years of age. 3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy with local confirmation of the presence of the EGFR exon 20 insertion mutation 4. Disease progression while on standard chemotherapy (platinum doublet chemotherapy or single-agent chemotherapy in selected patients) 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 6. Patients must have a life expectancy ≥ 12 weeks 7. Females should be using adequate contraceptive measures, should not be breast feeding 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: 8. Male patients should be willing to use barrier contraception 9. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 10. At least one measurable lesion 11. Provision of archival FFPE tissue 12. Provision of informed consent for translational genetic research
Exclusion criteria
1. Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site) 2. Previous treatment with osimertinib (3rd generation EGFR TKIs such as olumtinib, EGF816 etc) 3. Treatment with an investigational drug within five half-lives of the compound 4. Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inhibitors of CYP3A4 (at least 1 week prior) and potent inducers of CYP3A4 (at least 3 week prior) (Appendix A). All patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer/inhibitory effects on CYP3A4. 5. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy. 6. 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 including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 7. Patients with symptomatic CNS metastases who are neurologically unstable; however, those with asymptomatic CNS metastases who do not require steroids for at least 4 weeks prior to start of osimertinib are eligible. 8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD 9. Inadequate bone marrow reserve or organ function 10. QTc prolongation (mean resting corrected QTc \> 470 msec) 11. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of osimertinib 12. History of hypersensitivity to osimertinib (or drugs with a similar chemical structure or class to osimertinib) or any excipients of these agents 13. Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to study entry 14. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements 15. Previous allogeneic bone marrow transplant. 16. Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Until study completion, from date of initiation until the date of first documented progression, unacceptable toxicities or withdrawl, whichever came first. (upto about 29months) | Investigator-assessed, confirmed objective response by RECIST version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Events | From date of initiation until the date of first documented progression, unacceptable toxicities or withdrawal, whichever came first. Until study completion. (upto about 29months) | AEs/SAEs as defined by NCI CTCAE version 4.0 |
| Progression-free Survival | From date of initiation until the date of first documented progression, unacceptable toxicities or withdrawl, whichever came first. Until study completion. (upto about 29months) | PFS as defined by RECIST version 1.1 |
| Overall Survival | From the first date of IP administration to the date of death. (upto about 29months) | OS as defined by RECIST version 1.1. The time from the first date of IP administration to the date of death. |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Osimertinib Osimertinib at 80mg dose will be administered orally once daily.
Osimertinib 80 MG \[Tagrisso\]: Osimertinib 80mg once daily until disease progression | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Osimertinib |
|---|---|
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment South Korea | 15 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 8 / 15 |
Outcome results
Primary
Objective Response Rate
Investigator-assessed, confirmed objective response by RECIST version 1.1
Time frame: Until study completion, from date of initiation until the date of first documented progression, unacceptable toxicities or withdrawl, whichever came first. (upto about 29months)
Population: The proportion of patients who had complete reponse (CR) and partial reponse (PR) as the best response among 80mg osimertinib administered 15 patients.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Osimertinib | Objective Response Rate | 0 Participants |
Secondary
Overall Survival
OS as defined by RECIST version 1.1. The time from the first date of IP administration to the date of death.
Time frame: From the first date of IP administration to the date of death. (upto about 29months)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib | Overall Survival | 6.5 months |
Secondary
Progression-free Survival
PFS as defined by RECIST version 1.1
Time frame: From date of initiation until the date of first documented progression, unacceptable toxicities or withdrawl, whichever came first. Until study completion. (upto about 29months)
Population: The PFS rate at the time of data cutoff (10 June 2020) for 80mg osimertinib administered 15 patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib | Progression-free Survival | 3.8 months |
Secondary
Serious Adverse Events
AEs/SAEs as defined by NCI CTCAE version 4.0
Time frame: From date of initiation until the date of first documented progression, unacceptable toxicities or withdrawal, whichever came first. Until study completion. (upto about 29months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Osimertinib | Serious Adverse Events | General weakness | 1 cases |
| Osimertinib | Serious Adverse Events | Acute urinary retention | 1 cases |
| Osimertinib | Serious Adverse Events | Pneumonia | 2 cases |
| Osimertinib | Serious Adverse Events | Colitis | 1 cases |
| Osimertinib | Serious Adverse Events | Azotemia | 1 cases |
| Osimertinib | Serious Adverse Events | Hypercalcemia | 1 cases |
| Osimertinib | Serious Adverse Events | Femur fracture | 1 cases |