AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy. (ADAURA)

AstraZeneca

Status and phase: Active, not recruiting; Phase 3

Conditions: Stage IB-IIIA Non-small Cell Lung Carcinoma

Treatments: Drug: Open-label AZD9291 80 mg/40 mg; Drug: AZD9291 80 mg/40 mg; Drug: Placebo AZD9291 80 mg/40 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02511106

2023-506524-82-00 (Registry Identifier)

D5164C00001

2015-000662-65 (EudraCT Number)

Details and patient eligibility

About

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

Full description

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.

Enrollment: 682 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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682 participants in 2 patient groups, including a placebo group

AZD9291

Experimental group

Description:

AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.

Treatment:

Drug: AZD9291 80 mg/40 mg

Drug: Open-label AZD9291 80 mg/40 mg

Placebo AZD9291

Placebo Comparator group

Description:

Matching placebo for AZD9291 (80 mg or 40 mg orally, once daily), in accordance with the randomization schedule.

Treatment:

Drug: Placebo AZD9291 80 mg/40 mg