| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Non-small Cell Lung Cancer Tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
| Non-small Cell Lung Cancer Tumors |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025054 |
| E.1.2 | Term | Lung cancer non-small cell stage IIIB |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10025055 |
| E.1.2 | Term | Lung cancer non-small cell stage IV |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the progression free survival (PFS), based on independent radiologic review (IRR), of ASP8273 compared to erlotinib or gefitinib in patients with locally advanced, metastatic or unresectable stage IIIB/IV adenocarcinoma non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) activating mutations. |
|
| E.2.2 | Secondary objectives of the trial |
- Overall survival (OS)
- Overall response rate (ORR) as assessed by IRR
- PFS as assessed by the investigator
- Disease control rate (DCR) as assessed by IRR
- Duration of Response (DOR) as assessed by IRR
- Safety of ASP8273
- To evaluate Quality of Life (QoL) and patient-reported outcome (PRO) parameters as measured by FACT-EGFRI-18, EORTC-LQ-LC13, EORTCQLQ-C30 and EQ-5D-5L |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Retrospective PGx Substudy |
|
| E.3 | Principal inclusion criteria |
Subject must meet all of the following inclusion criteria to be eligible for participation in this study at enrollment:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) must be obtained from the subject or legally authorized representative prior to any
study-related procedures.
2. Subject is ≥ 18 years of age and legally an adult according to local regulation at the time of signing informed consent.
3. Subject agrees not to participate in another interventional study while on treatment.
4. Female subject must either:
Be of nonchildbearing potential:
- postmenopausal (defined as at least 1 year without any menses) prior to Screening, or
- documented surgically sterile
Or, if of childbearing potential:
- Agree not to try to become pregnant during the study and for 28 days after the final study drug administration
- And have a negative serum pregnancy test at Screening
- And, if heterosexually active, agree to consistently use 2 forms of birth control* (at least 1 of which must be a highly effective method* and one must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration
5. Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
6. Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
7. Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control* (1 of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.
*Acceptable forms of birth control include:
- Consistent and correct usage of established oral, injected or implanted hormonal methods of contraception
- Established intrauterine device (IUD) or intrauterine system (IUS)
- Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository (not applicable in Japan and Thailand: with spermicidal foam/gel film/cream/suppository)
- Calendar-based contraceptive methods (Knaus-Ogino or rhythm method [Japan and Thailand only])
8. Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
9. Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
10. Subject has histologically confirmed locally advanced, metastatic or unresectable Stage IIIB/IV adenocarcinoma NSCLC (newly diagnosed or recurrent). Subjects with mixed histology are eligible if adenocarcinoma is the predominant histology.
11. Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
12. Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.
- Neutrophil count > 1,000/mm^3
- Platelet count ≥ 7.5 x 10^4 /mm^3
- Hemoglobin > 8.0 g/dL
- Serum creatinine < 2.0 x upper limit of normal (ULN) or an estimated glomerular filtration rate (eGFR) of > 50 mL/min as calculated by the Cockcroft Gault Method
Total bilirubin < 1.5 x ULN (except for subjects with documented Gilbert’s syndrome)
AST and ALT < 3.0 x ULN or ≤ 5 x ULN if subject has documented liver metastases
Serum sodium level is ≥ 130 mmol/L
13. Subject has an EGFR activating mutation (exon 19 deletion or exon 21 L858R), with or without T790M mutation, by local or central testing on examination of a NSCLC FFPE specimen (archival or fresh biopsy)
Subjects harboring both exon 19 deletion and exon 21 L858R mutations are not eligible. A tissue sample from the same block used to determine eligibility by local testing should be available to send to the central lab for confirmatory testing. Subjects randomized based on local results indicating presence of EGFR mutations may remain on study if central results are discordant.
14. Subject must have at least 1 measureable lesion based on RECIST V1.1. Previously irradiated lesions will not be considered as measurable lesions. |
|
| E.4 | Principal exclusion criteria |
Subject who meets any of the following exclusion criteria prior to enrollment is not eligible for enrollment:
1. Subject has received intervening anticancer treatment or previous treatment with chemotherapy for metastatic disease other than palliative local radiation to painful bone metastases completed at least 1 week prior to the first dose of study drug. The administration of neoadjuvant or adjuvant chemotherapy is allowed as long as it has finalized ≥ 6 months before the first dose of study drug.
2. Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g., afatinib, dacomitinib, ASP8273, etc).
3. Subject has received investigational therapy within 28 days or 5 half-lives prior to the first dose of study drug.
4. Subject has received radiotherapy within 1 week prior to the first dose of study drug. If the subject received radiotherapy > 1 week prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.
5. Subject has symptomatic central nervous system (CNS) metastasis. Subject with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute effects of radiotherapy, does not have brain metastasis related symptoms, is not requiring systemic steroid, for at least 2 weeks prior to study drug administration, and any whole brain radiation therapy was completed at least 4 weeks prior to study drug administration, or any stereotactic radiosurgery (SRS) was completed at least 2 weeks prior to the first dose of study drug. Steroid inhaler use or ointment treatment for other concomitant medical disease is permitted.
6. Subject has received blood transfusions or hematopoietic factor therapy within 14 days prior to the first dose of study drug.
7. Subject has had a major surgical procedure (other than a biopsy) within 14 days prior to the first dose of study drug, or one is planned during the course of the study.
8. Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
9. Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8273, erlotinib or gefitinib.
10. Subject has evidence of an active infection requiring systemic therapy within 14 days prior to the planned first dose of study drug.
11. Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
12. Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
13. Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any
grade.
14. Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
15. Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
16. Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
17. Subject has concurrent corneal disorder or any ophthalmologic condition which, in the investigator’s opinion, makes the subject unsuitable for study participation (i.e., advanced cataracts, glaucoma).
18. Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
19. Subject has another past or active malignancy which requires treatment. Prior carcinoma in situ or non-melanoma skin cancer after curative resection are permitted.
20. Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
21. Subject has received potent CYP 3A4 inhibitors within 7 days prior to first dose of study drug or proton pump inhibitors such as omeprazole within 14 days prior to first dose of study drug |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- OS
- Best overall response rate (CR + PR) by IRR
- PFS by the investigator
- DCR (CR+PR+SD) by IRR
- DOR by IRR
- Safety variables (e.g., adverse events [AEs], laboratory tests, vital sign measurements, electrocardiograms [ECGs])
- QoL and PRO parameters |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 120 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Belgium |
| Brazil |
| Canada |
| Chile |
| France |
| Germany |
| Hungary |
| Italy |
| Japan |
| Korea, Republic of |
| Malaysia |
| Netherlands |
| Peru |
| Portugal |
| Romania |
| Russian Federation |
| Singapore |
| Spain |
| Taiwan |
| Thailand |
| Ukraine |
| United Kingdom |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study completion is defined as the conclusion of data collection for the defined study endpoints. Subjects continuing to derive clinical benefit are allowed to continue to receive treatment after study completion. End of study in all participating countries is therefore defined as the LSLV or last contact. The study may be closed within a participating country per local regulations after the study has completed if all subjects enrolled in the country are no longer receiving study treatment. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 18 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 22 |
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