Phase 1
Completed N=31
Phase I, Study in Chinese NSCLC Patients
Carcinoma, Non-Small-Cell Lung With EGFR Mutation Positive
Source: ClinicalTrials.gov NCT02529995 ↗
Enrolled (actual)
31
Serious AEs
25.8%
Results posted
Mar 2017
Primary outcomePrimary: Cmax of AZD9291 After Single Dosing — 103.8; 195.9 nmol/L
Summary
A Phase I, Open-Label, Two Parts Study to Assess the Safety, Tolerability,Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Chinese Patients with Advanced Non-Small Cell Lung Cancer who have Progressed Following Prior Therapy with an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Agent
Study Objective: 1, Primary Objective To characterise the pharmacokinetics (PK) of AZD9291 and its metabolites (AZ5104 and AZ7550) after single then multiple doses of AZD9291 administered orally once daily in Chinese patients with locally advanced or metastatic non small cell lung Cancer (NSCLC) who have progressed following prior therapy with an approved Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) agent.
2, Secondary objective(s) To investigate the safety and tolerability of AZD9291 when given orally to Chinese patients with locally advanced or metastatic NSCLC who have progressed following prior therapy with an approved EGFR TKI agent. To obtain a preliminary assessment of the anti-tumour activity of AZD9291 by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cmax of AZD9291 After Single Dosing |
103.8; 195.9 | — |
| PRIMARY Cmax of AZ5104 After Single Dosing |
4.207; 9.582 | — |
| PRIMARY Cmax of AZ7550 After Single Dosing |
3.443; 7.842 | — |
| PRIMARY AUC of AZD9291 After Single Dosing |
6323; 10260 | — |
| PRIMARY AUC of AZ5104 After Single Dosing |
589.0; 1077 | — |
| PRIMARY AUC of AZ7550 After Single Dosing |
527.4; 1292 | — |
| PRIMARY CL/F of AZD9291 After Single Dosing |
14.30; 16.45 | — |
| PRIMARY C(ss, Max) of AZD9291 After Multiple Dosing |
303.4; 550.4 | — |
| PRIMARY C(ss, Max) of AZ5104 After Multiple Dosing |
29.43; 49.98 | — |
| PRIMARY C(ss, Max) of AZ7550 After Multiple Dosing |
25.91; 54.15 | — |
| PRIMARY AUC(ss) of AZD9291 After Multiple Dosing |
5698; 9570 | — |
| PRIMARY AUC(ss) of AZ5104 After Multiple Dosing |
561.5; 964.7 | — |
| PRIMARY AUC(ss) of AZ7550 After Multiple Dosing |
505.7; 1123 | — |
| PRIMARY CL(ss)/F of AZD9291 After Multiple Dosing |
15.74; 17.67 | — |
| SECONDARY Objective Response Rate (ORR) |
46.7; 75.0 | — |
Eligibility Criteria
Inclusion Criteria
- Provision informed consent
- Aged at least 18 years
- Histological or cytological confirmation diagnosis of NSCLC
- Locally advanced or metastatic NSCLC
- Radiological documentation of disease progression while on a previous continuous treatment with an approved EGFR TKI. In addition other lines of therapy may have been given
- Documented EGFR mutation (at any time since the initial diagnosis of NSCLC) known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q)
- World Health Organisation (WHO) performance status 0-1
- At least one lesion suitable for accurate repeated measurements
- Females
- Child bearing potential : should not be breast feeding, use adequate contraceptive measures for female patients with child-bearing potential, OR
- Have evidence of non-child-bearing potential that meet one of the following criteria at screening:
- Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments
- Women below 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the institution
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
- Male patients should be willing to use barrier contraception ie, condoms
Exclusion Criteria
- Treatment with any of the following (prior to first dose of study treatment)
- Treatment with an EGFR TKI within 8 days
- Any investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days
- Previous treatment with AZD9291, or a Thr790Met (T790M) directed EGFR TKIs
- Major surgery (excluding placement of vascular access) within 4 weeks
- Radiotherapy :
- Within 1 week if limited field of radiation for palliation of the first dose of study treatment
- Within 4 weeks if receiving radiation to more than 30% of the bone marrow or with a wide field of radiation
- Patients currently receiving (or unable to stop use at least 1 week) medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 3A4 (CYP3A4)
- Treatment with an investigational drug within five half-lives of the compound
- 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
- Spinal cord compression or brain metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment
- 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
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derivedQTc value
- Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, P wave to R wave (PR) interval >250 msec
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long (Q-T interval) QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication
Data sourced from ClinicalTrials.gov (NCT02529995). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.