To assess the efficacy and safety of AZD9291 versus Placebo, in patients with Epidermal Growth Factor Receptor Mutation Positive stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy
Active, not recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| AZD9291 80 mg/40 mg | AZD9291 | |
| Placebo AZD9291 80 mg/40 mg | Placebo AZD9291 | |
| Open-label AZD9291 80 mg/40 mg | AZD9291 |
This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy
and safety of AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung
cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and
L858R) either alone or in combination with other EGFR mutations as confirmed by a central
test, who have had complete tumour resection, with or without postoperative adjuvant
chemotherapy. Adjuvant chemotherapy should have consisted of a platinum based doublet given
for a maximum of 4 cycles.
| Name | Type | Description | Interventions |
|---|---|---|---|
| AZD9291 | Experimental | AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. |
|
| Placebo AZD9291 | Placebo Comparator | Matching placebo for AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule. |
|
Inclusion Criteria:
1. Male or female, aged at least 18 years.
2. Histologically confirmed diagnosis of primary non small lung cancer (NSCLC) on
predominantly non-squamous histology
3. MRI or CT scan of the brain must be done prior to surgery as it is considered standard
of care.
4. Patients must be classified post-operatively as Stage IB, II or IIIA on the basis of
pathologic criteria.
5. Confirmation by the central laboratory that the tumour harbours one of the 2 common
EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R),
either alone or in combination with other EGFR mutations including T790M.
6. Complete surgical resection of the primary NSCLC is mandatory. All gross disease must
have been removed at the end of surgery. All surgical margins of resection must be
negative for tumour.
7. Complete recovery from surgery and standard post-operative therapy (if applicable) at
the time of randomization.
8. World Health Organization Performance Status of 0 to 1.
9. Female patients should be using adequate contraceptive measures, should not be breast
feeding, and must have a negative pregnancy test prior to first dose of study drug; or
female patients must have an evidence of non-child-bearing potential.
Exclusion Criteria:
1. Treatment with any of the following:
- Pre-operative or post-operative or planned radiation therapy for the current lung
cancer
- Pre-operative (neo-adjuvant) platinum based or other chemotherapy
- Any prior anticancer therapy
- Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
- Major surgery (including primary tumour surgery, excluding placement of vascular
access) within 4 weeks of the first dose of study drug
- Patients currently receiving medications or herbal supplements known to be potent
inducers of cytochrome P450 (CYP) 3A4
- Treatment with an investigational drug within five half-lives of the compound or
any of its related material.
2. Patients who have had only segmentectomies or wedge resections
3. History of other malignancies, except: adequately treated non-melanoma skin cancer,
curatively treated in-situ cancer, or other solid tumours curatively treated with no
evidence of disease for > 5 years following the end of treatment.
4. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
starting study treatment with the exception of alopecia and Grade 2, prior
platinum-therapy related neuropathy.
5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension and active bleeding diatheses; or active infection including hepatitis B,
hepatitis C and human immunodeficiency virus (HIV).
6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to
swallow the formulated product, or previous significant bowel resection that would
preclude adequate absorption of AZD9291.
7. Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using
the screening clinic ECG machine-derived QTc value.
- Any clinically important abnormalities in rhythm, conduction, or morphology of
resting ECG.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events, or unexplained sudden death under 40 years of age in first-degree
relatives or any concomitant medication known to prolong the QT interval.
8. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required
steroid treatment, or any evidence of clinically active ILD.
9. Inadequate bone marrow reserve or organ function.
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Assess the Efficacy of AZD9291 Compared to Placebo as Measured by Disease Free Survival (DFS). |
| Time Frame: | From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 4 years. |
| Safety Issue: | |
| Description: | Defined as the time from the date of randomization until the date of disease recurrence or death (by any cause in the absence of recurrence) |
| Measure: | Disease Free Survival (DFS) Rate at 2, 3 and 5 Years |
| Time Frame: | From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence), up to approximately 4 years. Assessed at 2 years and 3 years. |
| Safety Issue: | |
| Description: | Defined as the percentage of patients alive and disease free at 2, 3 and 5 years, respectively, estimated from Kaplan Meier plots of the primary endpoint of DFS at the time of the primary analysis |
| Measure: | Overall Survival (OS) |
| Time Frame: | From date of randomization until date of death due to any cause, up to approximately 4 years. |
| Safety Issue: | |
| Description: | Defined as the time from the date of randomization until date of death due to any cause. |
| Measure: | Overall Survival (OS) |
| Time Frame: | From date of randomization until date of death due to any cause, up to approximately 4 years. |
| Safety Issue: | |
| Description: | Defined as the time from the date of randomization until date of death due to any cause |
| Measure: | Overall Survival Rate at 2, 3 and 5 Years |
| Time Frame: | From date of randomization until date of death due to any cause, up to approximately 4 years. Assessed at 2 years and 3 years. |
| Safety Issue: | |
| Description: | Defined as the percentage of patients alive at 2, 3 and 5 years, respectively, estimated from a Kaplan Meier plot of OS at the time of the primary analysis |
| Measure: | Patient Health-related Quality of Life and Symptoms (HRQoL) by SF-36v2 Health Survey. |
| Time Frame: | Measured by SF-36 Questionnaire at baseline, 12 week, 24 week and then every 24 weeks until study complete, disease recurrence or other discontinuation criteria met, up to approximately 3 years. |
| Safety Issue: | |
| Description: | Change from baseline will be calculated for each domain and summary scale at each scheduled post-baseline assessment. The SF-36 includes eight domains: Physical Functioning (PF); Role Limitations-Physical (RP), Vitality (VT), General Health Perceptions (GH), Bodily Pain (BP), Social Function (SF), Role Limitations-Emotional (RE), and Mental Health (MH) and two summary scores: The Physical Component Summary (PCS) and Mental Component Summary (MCS). Final scores for each scale range from 0-100 with higher scores indicating better health. |
| Measure: | Plasma Concentrations of AZD9291 |
| Time Frame: | Collected at pre-dose, 0.5-1.5hours and 2-4hours post-dose up to 96 weeks (approximately 24 months) |
| Safety Issue: | |
| Description: | The pharmacokinetics exposure parameters derived from plasma concentrations of AZD9291 |
| Measure: | Plasma Concentrations of AZ5104 Metabolites |
| Time Frame: | From date of dosing to week 96 (approximately 24 months) |
| Safety Issue: | |
| Description: | The pharmacokinetics exposure parameters derived from plasma concentrations of AZ5104 metabolites |
| Measure: | Plasma Concentrations of AZ7550 Metabolites |
| Time Frame: | From date of dosing to week 96 (approximately 24 months) |
| Safety Issue: | |
| Description: | The pharmacokinetics exposure parameters derived from plasma concentrations of AZ7550 metabolites |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | AstraZeneca |
July 27, 2021
