臨床研究等提出・公開システム

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy

ORCHARD

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

completed

June. 25, 2019

Interventional

Non-Randomized, Parallel Assignment

treatment purpose

2

Inclusion criteria applicable to all study treatment modules (Groups A/B):

1.Non-Small Cell Lung Cancer (NSCLC) with the following features

1.Locally advanced or metastatic disease (i.e., advanced NSCLC) not amenable to curative surgery or radiotherapy at study entry.

2. Histologically or cytologically confirmed adenocarcinoma of the lung (patients with mixed histology are eligible if adenocarcinoma is the predominant histology) harboring EGFR mutation(s) known to be associated with EGFR TKI sensitivity at diagnosis. Any histologically identifiable component of neuroendocrine transformation to SCLC or large cell NEC is required for treatment under Module 7.

3. Received only 1 line of therapy, with single-agent osimertinib, for advanced NSCLC, with clinical benefit as judged by investigator discretion.

(Note: a 'line' of therapy is defined as a daily anti-cancer treatment administered for >14 days, or a single infusion of an intravenous anti-cancer treatment. For instance, patients who have had <14 days of a first- or second- generation TKI prior to osimertinib, and stopped due to adverse events, would be eligible to enter this study, see also exclusion criteria 5).

Patients previously treated adjuvantly or neo-adjuvantly are eligible per exclusion criterion 5.

4.Evidence of radiological disease progression on first-line monotherapy with osimertinib 80 mg po QD.

2. Suitable for a mandatory biopsy defined as having an accessible tumor; by whichever modality the site uses and, ideally, confirmed by the person who will perform the procedure; and a stable clinical condition that will allow the patient to tolerate the procedure. The biopsy should be performed within 60 days of the planned first dose of study treatment.

3.Patients must have measurable disease per RECIST 1.1, as defined by at least 1 lesion that can be accurately measured at baseline as 10 mm or more at the longest diameter (except lymph nodes which must have a short axis 15 mm or more) with computed tomography (CT) or magnetic resonance imaging (MRI), which is suitable for accurate repeated measurements. Previously irradiated lesions or a lesion in the field of radiation should not be used as measurable disease unless the lesion(s) has/have demonstrated unequivocal disease progression by RECIST 1.1. Target lesions should not be used for the baseline tumour biopsy, unless there are no other lesions suitable for biopsy and they fulfil requirements.

4. Adequate coagulation parameters, defined as:
International Normalisation Ratio (INR) <1.5 x ULN and activated partial thromboplastin time <1.5 x ULN unless patients are receiving therapeutic anti-coagulation which affects these parameters.

Exclusion Criteria applicable to all study treatment modules (Groups A/B):

1. Patients whose disease has progressed within the first 3 months of osimertinib treatment.(refractory to osimertinib treatment).

2. Patients must not have experienced a toxicity(-ies) that led to permanent discontinuation or dose reduction of prior osimertinib.
(a) Patients who had dose reductions in the past, but were receiving a full dose of osimertinib at the time of pre-screening should be discussed with the Study Physician.

3. Any unresolved toxicities from prior osimertinib treatment greater than CTCAE Grade 1 at the time of starting study treatment.

4. Patients should not have discontinued osimertinib >60 days prior to the first dose of study treatment.

5. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:

1. Absolute neutrophil count < 1.5 x 109/L.

2. Platelet count < 100 x 109/L.

3. Haemoglobin < 9 g/dL.

4. Alanine transaminase (ALT) > 2.5 x ULN.

5. Aspartate aminotransferase (AST) > 2.5 x ULN.

6. Total bilirubin (TBL) > 1.5 x ULN, or > 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinaemia).

6. Creatinine clearance (CrCl) < 50 mL/min, calculated using Cockcroft-Gault equation (Cockcroft and Gault 1976) or 24-hour urine collection.

Both

Non-Small Cell Lung Cancer

investigational material(s)
Generic name etc : Osimertinib, Savolitinib, Gefitinib, Necitumumab, Durvalumab, Carboplatin, Pemetrexed, Alectinib, Selpercatinib, Selumetinib, Etoposide, Datopotamab Deruxtecan
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : M1: osimerinib 80mg+savolitinib 300mg orally once daily
M2: osimertinib 80mg+gefitinib 250mg orally once daily
M3: osimertinib 80mg(orally)+necitumumab 800mg once daily as an intravenous(IV) infusion on Days1, 8 of each 21day cycle
M4: Durvalumab 1500mg+pemetrexed 500mg/m2+carboplatin AUC5 is IV infusion on the first day to 6cycles as a 21day cycle.And, Durvalumab+ pemetrexed can be IV infusion as 28days cycle
M5: osimertinib 80mg+alectinib 300mg orally twice daily

Generic name etc : Osimertinib, Savolitinib, Gefitinib, Necitumumab, Durvalumab, Carboplatin, Pemetrexed, Alectinib, Selpercatinib, Selumetinib, Etoposide, Datopotamab Deruxtecan
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material : M6: osimertinib 80mg+selpercatinib 160mg orally twice daily
M7: Durvalumab 1500mg+Etoposide 80-100mg/m2+carboplatin AUC5-6 is IV infusion on the first day to 4cycles as a 21day cycle.(Etoposide is administered on Days1-3). And, Durvalumab can be IV infusion as 28days cycle
M8: osimertinib 80mg(orally)+pemetrexed 500mg/m2+carboplatin AUC5 is IV infusion on the first day to 4cycles as a 21day cycle. And, osimertinib+pemetrexed can be administered as 21days cycle
M9: osimertinib 80mg+selumetinib 75mg orally twice daily
M10: osimertinib 80mg(orally)+ Datopotamab deruxtecan 4.0 mg/kg or 6.0 mg/kg can be IV infusion every 3 weeks.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
confirmatory
-

efficacy
pharmacokinetics
-

June. 13, 2019