Advanced Non Small Cell Lung CancerPhase 1NCT02143466
AZD9291 in Combination With Ascending Doses of Novel Therapeutics
A Phase 1 study testing Part A - AZD9291 in combination with AZD6094, Part A - AZD9291 in combination with continuous selumetinib (Asian subjects) and Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects) in people with Advanced Non Small Cell Lung Cancer, run by AstraZeneca at 42 sites in 8 countries.
Trial summary
The purpose of this study is to determine the safety, tolerability and preliminary anti-tumour activity of AZD9291 when given together with AZD6094 or selumetinib in patients with EGFR mutation positive advanced lung cancer Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Non Small Cell Lung Cancer
- What is being tested?
- Part A - AZD9291 in combination with AZD6094, Part A - AZD9291 in combination with continuous selumetinib (Asian subjects) and Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 344 participants
- Where
- 42 sitesin 8 countries
- Study dates
- 5 Aug 2014to 31 Dec 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria Signed informed consent Male or female aged at least 18 years and older. Patients from Japan aged at least 20 years.
Histological or cytological confirmation of EGFRm+ NSCLC. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including exon 19 deletion and L858R). Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI eg, gefitinib or erlotinib. These patients must have radiological progression (as per site assessment) on the last treatment administered prior to enrolling in the study.
At least one lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. Adequate haematological, liver and renal function as well as coagulation parameters.
ECOG/WHO performance status of 0 or 1 or KPS >80. Ability to swallow and retain oral medications. Prior to study entry, local confirmation of tumour cMET status is acceptable, a central result will be confirmed retrospectively. Local confirmation of tumour T790M status is acceptable if performed with an approved test and agreed by AstraZeneca.
Agree to use adequate contraceptive measures.
Exclusion Criteria Treatment with an EGFR TKI within approximately 5x half-life (eg, within 8 days for erlotinib, gefitinib or afatanib, or within 10 days for dacomitinib) of the first dose of study treatment. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment Patients currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior). For AZD6094 patients currently receiving prior to receiving the first dose, medications known to be strong inhibitors of CYP1A2.
Prior AZD9291 dosing in the present study. Prior treatment with a 3rd generation (T790M-directed) therapy (eg, AZD9291, rociletinib or HM61713) outside of this study is permitted if allocated to the 3rd generation EGFR TKI cohort. Prior or current treatment with AZD6094 or another cMET inhibitor (eg, foretinib, crizotinib, cabozantinib, onartuzumab) if allocated to AZD9291 plus AZD6094 combination. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within ≥4 weeks of the first dose of study treatment Major surgical procedure, or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study.
Currently receiving treatment with warfarin sodium. LMWH is allowed. Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy Any of the following cardiac diseases currently or within the last 6 months: Unstable angina pectoris, Congestive heart failure (NYHA ≥ Grade 2), Acute myocardial infarction, Stroke or transient ischemic attack.
Known hypersensitivity to the active or inactive excipients of AZD6094. Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy) Mean resting correct QT interval (QTcF) >470 msec for women and >450 msec for men or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms (ECGs), e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec. Serious underlying medical condition at the time of treatment that would impair the ability of the patient to receive protocol treatment.
Active hepatitis B (positive HBsAg result) or hepatitis C (HCV). Patients with a past or resolved HBV infection are eligible if negative for HBsAg and positive for anti-HBc or positive for HBsAg, but for > 6 months have had normal transaminases and HBV DNA levels between 0-2000 IU/ml (inactive carrier state) and willing to start and maintain antiviral treatment for at least the duration of the study. HBV DNA levels > 2000 IU/ml but on prophylactic antiviral treatment for the past 3 months and will maintain the antiviral treatment during the study. Patients with positive HCV antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
Known serious active infection including, but not limited to, tuberculosis, or human immunodeficiency virus (positive HIV 1/2 antibodies).
Presence of other active cancers, or history of treatment for invasive cancer, within the last 5 years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
Women who are either pregnant or breast feeding. Previous allogeneic bone marrow transplant 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.
Trial locations and contacts
42 sites in 8 countries.
42 sites in 8 countries
Russia9 sites
Research Site
Chelyabinsk, 454087
Research Site
Krasnoyarsk, 660133
Research Site
Moscow, 115478
Research Site
Omsk, 644013
Research Site
Saint Petersburg, 195271
Research Site
Saint Petersburg, 197002
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197342
Research Site
Saint Petersburg, 197758
United States6 sites
Research Site
Atlanta, Georgia, 30329
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Nashville, Tennessee, 37232
Research Site
New York, New York, 10065
Research Site
Philadelphia, Pennsylvania, 19111
Japan6 sites
Research Site
Chūōku, 104-0045
Research Site
Habikino-shi, 583-8588
Research Site
Hirakata-shi, 573-1191
Research Site
Kashiwa, 227-8577
Research Site
Nagoya, 460-0001
Research Site
Nagoya, 464-8681
South Korea6 sites
Research Site
Cheongju-si, 28644
Research Site
Goyang-si, 10408
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Taiwan6 sites
Research Site
Kaohsiung City, 82445
Research Site
Kaohsiung City, 83301
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 112
Research Site
Taipei, 235
Poland5 sites
Research Site
Gdansk, 80-952
Research Site
Krakow, 31-202
Research Site
Olsztyn, 10-357
Research Site
Poznan, 60-569
Research Site
Warsaw, 02-781
Canada2 sites
Research Site
Calgary, Alberta, T2N 4N2
Research Site
Edmonton, Alberta, T6G 1Z2
About this study
Official title: A Multi-arm, Phase Ib, Open-Label, Multicentre Study to Assess the Safety,Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients With EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI (TATTON).
The purpose of this study is to determine the safety, tolerability and preliminary anti-tumour activity of AZD9291 when given together with AZD6094 or selumetinib in patients with EGFR mutation positive advanced lung cancer
Read the detailed description
This is a Phase Ib, open-label, multicentre study of AZD9291 administered orally in combination with novel therapeutics (AZD6094 or selumetinib (AZD6244, ARRY142886)) to patients with EGFRm+ advanced NSCLC. The study has been designed to allow an investigation of the optimal combination dose and schedule whilst ensuring the safety of patients with intensive safety monitoring. There are three main parts to this study; Part A, Combination dose finding and Parts B and D, Dose expansion. Part C, AZD6094 dose finding sub-study in advanced solid tumour patients is ongoing in Japan.
AZD9291 (osimertinib) is a potent irreversible inhibitor of both the single epidermal growth factor receptor sensitising mutation positive (EGFRm+) (tyrosine kinase inhibitor [TKI] sensitivity-conferring mutation) and dual EGFRm+/T790M+ (TKI resistance-conferring mutation) receptor forms of EGFR. AZD9291 therefore has the potential to provide clinical benefit to patients with advanced non-small cell lung cancer (NSCLC) harbouring both the single sensitivity mutations and the resistance mutation following prior therapy with an EGFR TKI. AZD9291 (osimertinib) was awarded FDA accelerated approval in November 2015, followed by conditional approval in the EU, full approval in Japan and additional markets in 2016, for the treatment of patients with EGFR T790M+ NSCLC who have progressed on or after EGFR TKI therapy.
Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study.
.
- Conditions
- Advanced Non Small Cell Lung Cancer
- Being tested
- Part A - AZD9291 in combination with AZD6094, Part A - AZD9291 in combination with continuous selumetinib (Asian subjects), Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects), Part A - AZD9291 in combination with intermittent selumetinib, Part A - AZD9291 in combination with MEDI4736
- Keywords
- Phase I, Safety, Tolerability, Efficacy, Anti-tumour, AZD9291, AZD6094, MEDI4736, Osimertinib, Savolitinib, Selumetinib, Durvalumab, Ascending Doses, Expansion cohorts, EGFR, Advanced Non-Small Cell Lung Cancer, Tyrosine Kinase Inhibitors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part A - AZD9291 in combination with AZD6094Drug
Also called Osimertinib & Savolitinib/Volitinib
Part A - AZD9291 and AZD6094 administered in different doses to investigate the safety and tolerability of this combination and define the combination dose for further clinical evaluation in Part B.
Part A - AZD9291 in combination with continuous selumetinib (Asian subjects)Drug
Also called Osimertinib & ARRY-142886
Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in Asian subjects and to define the combination dose for further clinical evaluation in Part B.
Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects)Drug
Also called Osimertinib & ARRY-142886
Part A - AZD9291 and selumetinib (continuous treatment) administered in different doses to investigate the safety and tolerability of this combination in non-Asian subjects and to define the combination dose for further clinical evaluation in Part B.
Part A - AZD9291 in combination with intermittent selumetinibDrug
Also called Osimertinib & ARRY-142886
Part A - AZD9291 and selumetinib (intermittent treatment) administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B.
Part A - AZD9291 in combination with MEDI4736Drug
Also called Osimertinib & Durvalumab
Part A - AZD9291 and MEDI4736 administered in different doses to investigate the safety and tolerability of this combination and to define the combination dose for further clinical evaluation in Part B.
Note: Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study.
Part B - AZD9291 in combination with AZD6094Drug
Also called Osimertinib & Savolitinib/Volitinib
Part B - AZD9291 and AZD6094 administered in the dose identified in Part A (AZD9291 80mg OD + AZD6094 600mg OD) to further investigate the safety and tolerability of this combination.
Part B - AZD9291 in combination with selumetinibDrug
Also called Osimertinib & ARRY-142886
Part B - AZD9291 and selumetinib administered in the dose identified in Part A (AZD9291 80mg OD + selumetinib 75 mg BD intermittent [4 days on/3 days off]) to further investigate the safety and tolerability of this combination.
Part B - AZD9291 in combination with MEDI4736Drug
Also called Osimertinib & Durvalumab
Part B - AZD9291 and MEDI4736 administered in the dose identified in Part A to further investigate the safety and tolerability of this combination.
Note: Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study.
Part C - AZD6094 monotherapy (Japan only)Drug
Also called Savolitinib/Volitinib
Part C - AZD6094 monotherapy to assess the safety, tolerability and pharmacokinetics of the monotherapy of AZD6094 in Japanese patients with advanced NSCLC.
Part C - AZD9291 in combination with AZD6094 (Japan only)Drug
Also called Osimertinib & Savolitinib/Volitinib
Part C combination cohort - AZD9291 80mg OD administered in combination with AZD6094 400mg OD (AZD6094 dose in which DLTs have not been identified in the Japanese monotherapy cohort) in order to confirm the safety, tolerability, pharmacokinetics and preliminary anti-tumor activities of this combination in Japanese subjects. The 400mg OD dosing schedule will be initiated in the first cohort. The dose may be subsequently reduced in further cohorts in response to emerging safety, or PK findings or other reasons identified in the savolitinib programme.
Part D - AZD9291 in combination with AZD6094Drug
Also called Osimertinib & Savolitinib/Volitinib
Part D - AZD9291 80mg OD administered in combination with AZD6094 300mg OD to further evaluate the safety, tolerability, pharmacokinetics and antitumor activity in terms of ORR and PFS in patients with locally advanced or metastatic cMET positive EGFRm+ and T790M-negative NSCLC, following progression on EGFR-TKI treatment. The choice of AZD6094 dose of 300 mg is based on results from preclinical and clinical studies. Clinical testing of the 300 mg OD dose will enable better assessment of impact of lower AZD6094 exposure on overall tolerability and hepatotoxicity risk as well as exploration of the efficacy and overall safety profiles with a dose meaningfully lower than the current dose of 600 mg OD.
| Study group | Role | What they receive |
|---|---|---|
| AZD6094 | Experimental | AZD9291 in combination with AZD6094 Receives: Drug: Part A - AZD9291 in combination with AZD6094; Drug: Part B - AZD9291 in combination with AZD6094; Drug: Part C - AZD9291 in combination with AZD6094 (Japan only); Drug: Part D - AZD9291 in combination with AZD6094 |
| Selumetinib | Experimental | AZD9291 in combination with selumetinib Receives: Drug: Part A - AZD9291 in combination with continuous selumetinib (Asian subjects); Drug: Part A - AZD9291 in combination with continuous selumetinib (non-Asian subjects); Drug: Part A - AZD9291 in combination with intermittent selumetinib; Drug: Part B - AZD9291 in combination with selumetinib |
| MEDI4736 | Experimental | AZD9291 in combination with MEDI4736. Enrolment into the patient cohort that evaluated AZD9291 treatment in combination with MEDI4736 as 1st line treatment has been terminated due to an increased incidence of ILD-like events (interstitial lung disease/pneumonitis), and is no longer being evaluated in this study. Receives: Drug: Part A - AZD9291 in combination with MEDI4736; Drug: Part B - AZD9291 in combination with MEDI4736 |
| AZD6094 (monotherapy) | Experimental | AZD6094 in monotherapy (for Japan only) Receives: Drug: Part C - AZD6094 monotherapy (Japan only) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of AZD9291 when given in combination with AZD6094 or selumetinib
Part A: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 or selumetinib who have progressed following prior therapy with an EGFR TKI agent, and define the combination dose(s) for further clinical evaluation.
Measured: Adverse events will be collected from baseline until 28 days after the last dose in the AZD6094 or selumetinib arms.
Number of participants with Adverse Events as a measure of Safety and Tolerability of AZD9291 when given in combination with AZD6094 or selumetinib
Part B: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 or selumetinib in patients with locally advanced or metastatic NSCLC, who have progressed on prior therapy with an EGFR TKI agent.
Part C monotherapy cohort (Japan only): To investigate and confirm the safety and tolerability of AZD6094 when given orally to Japanese patients with advanced solid malignancies.
Part C combination cohort (Japan only): To investigate the safety and tolerability of AZD9291 when given orally to Japanese patients with EGFRm+ NSCLC in combination with AZD6094 who have progressed following prior therapy with an EGFR TKI agent, and define the combination dose(s) for further clinical evaluation.
Part D: To investigate the safety and tolerability of AZD9291 when given in combination with AZD6094 (300 mg OD) in patients with locally advanced or metastatic EGFRm+ NSCLC.
Measured: Adverse events: baseline until 28 days after the last dose in the AZD6094 or selumetinib arms.
Secondary outcomes (21)
Cmax after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
Tmax after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified on cycle 1 day 1 up to 24 hours
AUC after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
AUC0-t after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified on cycle 1 day 1 up to 24 hours
AUC0-24 after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
Terminal half life after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
CL/f after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
Volume of distribution after single dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 up to 24 hours
Cssmax after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 2 day 1 up to 24 hours
Tssmax after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 2 day 1 up to 24 hours
Cssmin after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times for the duration of treatment.
AUCss after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 2 day 1 up to 24 hours
CLss/f after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 2 day 1 up to 24 hours
Rac after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 and cycle 2 day 1
Time dependency of PK after multiple dosing
To characterise the pharmacokinetics of AZD9291, AZD6094 or selumetinib and metabolites after single dosing and at steady state after multiple dosing when AZD9291 is given orally in combination with AZD6094 or selumetinib (or, in case of Part C monotherapy for Japanese subjects, when AZD6094 is given alone) to patients with EGFRm+ NSCLC through plasma concentrations.
Measured: Blood samples will be collected from each subject at pre-specified times on cycle 1 day 1 and cycle 2 day 1
Objective response rate
To obtain a preliminary assessment of the anti-tumour activity of the combination of AZD9291 and AZD6094 or selumetinib by evaluation of tumour response (objective response rate, duration of response, change in tumour size) and progression free survival using RECIST version 1.1.
Measured: At baseline and every 6 weeks until disease progression or withdrawal from study.
Disease control rate
To obtain a preliminary assessment of the anti-tumour activity of the combination of AZD9291 and AZD6094 or selumetinib by evaluation of tumour response (objective response rate, duration of response, change in tumour size) and progression free survival using RECIST version 1.1
Measured: At baseline and every 6 weeks until disease progression or withdrawal from study.
Duration of response
To obtain a preliminary assessment of the anti-tumour activity of the combination of AZD9291 and AZD6094 or selumetinib by evaluation of tumour response (objective response rate, duration of response, change in tumour size) and progression free survival using RECIST version 1.1
Measured: At baseline and every 6 weeks until disease progression or withdrawal from study.
Percentage change in tumour size
To obtain a preliminary assessment of the anti-tumour activity of the combination of AZD9291 and AZD6094 or selumetinib by evaluation of tumour response (objective response rate, duration of response, change in tumour size) and progression free survival using RECIST version 1.1
Measured: At baseline and every 6 weeks until disease progression or withdrawal from study.
Progression free survival
To obtain a preliminary assessment of the anti-tumour activity of the combination of AZD9291 and AZD6094 or selumetinib by evaluation of tumour response (objective response rate, duration of response, change in tumour size) and progression free survival using RECIST version 1.1 Expansion phase only
Measured: At baseline and every 6 weeks until disease progression or withdrawal from study.
Overall survival
To obtain a preliminary assessment of overall survival in the AZD9291+AZD6094 combination arms of the study for Parts B and D.
Measured: Confirmed during the FUP period and at least every 12 weeks until the data cut-off for the primary analysis and determination that no further OS collection is needed, approximately 5 years, death, or full withdrawal of consent, whichever comes first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2014 (estimated)
- Study start5 Aug 2014
- Primary completion4 Mar 2020
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Advanced Non Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 344 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pasi A Jänne, MD, PhD, Principal investigator, Dana-Faber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02143466
- Sponsor's protocol ID
- D5160C00006
- Other IDs
- 2016-004752-29, 2016
- Status last verified
- Oct 2026
- First submitted
- 9 May 2014
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Publications
Ahn MJ, Cho BC, Ou X, Walding A, Dymond AW, Ren S, Cantarini M, Janne PA. Osimertinib Plus Durvalumab in Patients With EGFR-Mutated, Advanced NSCLC: A Phase 1b, Open-Label, Multicenter Trial. J Thorac Oncol. 2022 May;17(5):718-723. doi: 10.1016/j.jtho.2022.01.012. Epub 2022 Feb 15.
PubMed 35181499Yoh K, Hirashima T, Saka H, Kurata T, Ohe Y, Hida T, Mellemgaard A, Verheijen RB, Ou X, Ahmed GF, Hayama M, Sugibayashi K, Oxnard GR. Savolitinib +/- Osimertinib in Japanese Patients with Advanced Solid Malignancies or EGFRm NSCLC: Ph1b TATTON Part C. Target Oncol. 2021 May;16(3):339-355. doi: 10.1007/s11523-021-00806-5. Epub 2021 May 3.
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