A Study of ASP8273 vs. Erlotinib or Gefitinib in First-line Treatment of Patients With Stage IIIB/IV Non-small Cell Lung Cancer Tumors With EGFR Activating Mutations

NCT ID: NCT02588261

Last Updated: 2024-12-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 530 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-11
• Study Completion Date: 2017-12-21

Brief Summary

The purpose of the study was 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.

This study also assessed 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) by IRR; Safety of ASP8273; and Quality of Life (QOL) and patient-reported outcome (PRO) parameters.

Conditions

Non-small Cell Lung Cancer (NSCLC)

Keywords

erlotinib; EGFR mutation; naquotinib; Non-small cell lung cancer (NSCLC); ASP8273; gefitinib

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ASP8273

Participants received 300 mg of ASP8273 orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).

Group Type: EXPERIMENTAL

naquotinib mesilate

Intervention Type: DRUG

Participants received ASP8273 300 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day.

erlotinib or gefitinib

Participants received 150 mg of erlotinib or 250 mg of gefitinib orally once daily in 28-day cycles until one of the discontinuation criteria was met (developed radiological progressive disease, required to receive local or systemic anti-cancer treatment, developed unacceptable toxicity, participant pregnancy, investigator decision, required to receive significant surgical procedure, participant protocol deviation or noncompliance, participant decline of further treatment and participant lost to follow-up).

Group Type: ACTIVE_COMPARATOR

Erlotinib

Intervention Type: DRUG

Participants received erlotinib 150 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Gefitinib

Intervention Type: DRUG

Participants received gefitinib 250 mg was taken orally once daily with water, with or without food, at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Interventions

naquotinib mesilate

Participants received ASP8273 300 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day.

Intervention Type: DRUG

Erlotinib

Participants received erlotinib 150 mg orally once daily on an empty stomach (no food for at least 2 hours before and 1 hour after taking drug) at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Intervention Type: DRUG

Gefitinib

Participants received gefitinib 250 mg was taken orally once daily with water, with or without food, at approximately the same time every day. At the beginning of the trial, prior to site initiation and shipment of study drug supplies, each investigator selected either erlotinib or gefitinib to be utilized for all participants randomized to the comparator arm at their site.

Intervention Type: DRUG

Other Intervention Names

ASP8273; Tarceva; OSI-774

Eligibility Criteria

Inclusion Criteria

• Subject agrees not to participate in another interventional study while on treatment.
• 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 highly effective 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.
• Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.
• Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.
• 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.
• Male subject must not donate sperm starting at Screening and throughout the study period and for 90 days after the final study drug administration.
• Subject has Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• 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.
• Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
• 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/mm3
• Platelet count ≥ 7.5 x 104 /mm3
• 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
• 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 mutation may remain on study if central results are discordant.
• Subject must have at least 1 measureable lesion based on RECIST V1.1. Previously irradiated lesions will not be considered as measurable lesions.

Exclusion Criteria

• 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.
• Subject has received a prior treatment with a therapeutic agent targeting EGFR (e.g., afatinib, dacomitinib, ASP8273, etc).
• Subject has received investigational therapy within 28 days or 5 half-lives prior to the first dose of study drug.
• 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.
• 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 steroids 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 study drug administration. Steroid inhaler use or ointment treatment for other concomitant medical disease is permitted.
• Subject has received blood transfusions or hematopoietic factor therapy within 14 days prior to the first dose of study drug.
• 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.
• Subject has a known history of a positive test for human immunodeficiency virus (HIV) infection.
• Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8273, erlotinib or gefitinib.
• Subject has evidence of an active infection requiring systemic therapy within 14 days prior to the planned first dose of study drug.
• Subject has severe or uncontrolled systemic diseases including uncontrolled hypertension (blood pressure > 150/100 mmHg) or active bleeding diatheses.
• Subject has history of drug-induced interstitial lung disease (ILD) or any evidence of active ILD.
• Subject has ongoing cardiac arrhythmia that is Grade ≥ 2 or uncontrolled atrial fibrillation of any grade.
• Subject currently has Class 3 or 4 New York Heart Association congestive heart failure.
• Subject has history of severe/unstable angina, myocardial infarction or cerebrovascular accident within 6 months prior to the planned first dose of study drug.
• Subject has history of gastrointestinal ulcer or gastrointestinal bleeding within 3 months prior to the planned first dose of study drug.
• 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).
• Subject has difficulty taking oral medication or any digestive tract dysfunction or inflammatory bowel disease that would interfere with the intestinal absorption of drug.
• Subject has another past or active malignancy which requires treatment. Prior carcinoma in situ or non-melanoma skin cancer after curative resection are permitted.
• Subject has any condition which, in the investigator's opinion, makes the subject unsuitable for study participation.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Global Development, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Astellas Pharma Global Development, Inc.

Locations

Site US10029

Beverly Hills, California, United States

Site US10025

Fountain Valley, California, United States

Site US10036

La Jolla, California, United States

Site US10051

Loma Linda, California, United States

Site US10033

Los Angeles, California, United States

Site US10031

Oxnard, California, United States

Site US10052

Redondo Beach, California, United States

Site US10003

Santa Monica, California, United States

Site US10018

Whittier, California, United States

Site US10047

Glenwood Springs, Colorado, United States

Site US10013

Aventura, Florida, United States

Site US10048

St. Petersburg, Florida, United States

Site US10050

Atlanta, Georgia, United States

Site US10042

Baton Rouge, Louisiana, United States

Site US10037

Scarborough, Maine, United States

Site US10034

Boston, Massachusetts, United States

Site US10030

Minneapolis, Minnesota, United States

Site US10027

Rochester, Minnesota, United States

Site US10045

Albuquerque, New Mexico, United States

Site US10012

Mount Kisco, New York, United States

Site US10021

Bethlehem, Pennsylvania, United States

Site US10009

Nashville, Tennessee, United States

Site US10023

Nashville, Tennessee, United States

Site US10011

Lacey, Washington, United States

Site US10046

Milwaukee, Wisconsin, United States

Site AU61003

Randwick, New South Wales, Australia

Site AU61007

Woolloongabba, Queensland, Australia

Site AU61005

Adelaide, South Australia, Australia

Site AU61008

East Melbourne, Victoria, Australia

Site AU61002

Fitzroy, Victoria, Australia

Site AU61004

Footscray, Victoria, Australia

Site BE32002

Ghent, West-Vlaanderen, Belgium

Site CA15006

Toronto, Ontario, Canada

Site CA15002

Montreal, Quebec, Canada

Site CL56002

Viña del Mar, Región de Valparaíso, Chile

Site CL56007

Viña del Mar, Región de Valparaíso, Chile

Site CL56001

Santiago, Región Metropolitana de Santia, Chile

Site FR33010

Pessac, Gironde, France

Site FR33011

Suresnes, Hauts-de-Seine, France

Site FR33003

Créteil, Ilej-de-France, France

Site FR33004

Tours, Indre-et-Loire, France

Site FR33006

Grenoble, Isère, France

Site FR33009

Saint Priest En Jarez, Pays de la Loire Region, France

Site FR33012

Bayonne, Pyrénées-Atlantiques, France

Site FR33007

Pierre-Bénite, Rhône, France

Site DE49008

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Site DE49005

Karlsruhe, Baden-Wurttemberg, Germany

Site DE49003

Gauting, Bavaria, Germany

Site DE49006

Würzburg, Bavaria, Germany

Site DE49007

Kassel, Hesse, Germany

Site DE49004

Cologne, North Rhine-Westphalia, Germany

Site HU36002

Székesfehérvár, Fejér, Hungary

Site HU36003

Tatabánya, Tatabánya, Hungary

Site HU36006

Szombathely, Vas County, Hungary

Site HU36004

Farkasgyepű, Veszprém megye, Hungary

Site HU36007

Budapest, , Hungary

Site HU36001

Budapest, , Hungary

Site IT39004

Monza, Lombardy, Italy

Site IT39009

Rozzano, Lombardy, Italy

Site IT39011

Aviano, Pordenone, Italy

Site IT39003

Bergamo, , Italy

Site IT39015

Brescia, , Italy

Site IT39002

Cremona, , Italy

Site IT39013

Lucca, , Italy

Site IT39014

Milan, , Italy

Site IT39012

Piacenza, , Italy

Site IT39008

Roma, , Italy

Site JP81018

Matsuyama, Ehime, Japan

Site JP81013

Hiroshima, Hirosima [Hiroshima], Japan

Site JP81014

Sapporo, Hokkaidô, Japan

Site JP81017

Osakasayama-shi, Hukuoka [Fukuoka], Japan

Site JP81008

Kurume, Hukuoka, Japan

Site JP81024

Kobe, Hyōgo, Japan

Site JP81015

Kanazawa, Isikawa [Ishikawa], Japan

Site JP81010

Yokohama, Kanagawa, Japan

Site JP81025

Yokohama, Kanagawa, Japan

Site JP81012

Sendai, Miyagi, Japan

Site JP81016

Kurashiki, Okayama-ken, Japan

Site JP81005

Miyakojima-ku, Osaka, Japan

Site JP81020

Osakasayama-shi, Osaka, Japan

Site JP81019

Sunto-gun, Shizuoka, Japan

Site JP81001

Sunto-gun, Sizuoka [Shizuoka], Japan

Site JP81004

Tokyo, Tôkyô [Tokyo], Japan

Site JP81022

Niigata, , Japan

Site JP81006

Okayama, , Japan

Site JP81023

Wakayama, , Japan

Site JP81021

Hirakata, Ôsaka [Osaka], Japan

Site JP81002

Ōsaka-sayama, Ôsaka [Osaka], Japan

Site MY60001

Kuantan Pahang, Pahang, Malaysia

Site MY60002

George Town, Pulau Pinang, Malaysia

Site MY60004

Kuching, Sarawak, Malaysia

Site NL31001

Arnhem, Gelderland, Netherlands

Site NL31006

Alkmaar, North Holland, Netherlands

Site PE51001

Cercado de Lima, Arequipa, Peru

Site PE51008

Miraflores, Lima region, Peru

Site PE51004

San Isidro, Lima region, Peru

Site PT35101

Amadora, Lisbon District, Portugal

Site PT35104

Lisbon, Lisbon District, Portugal

Site PT35103

Coimbra, , Portugal

Site PT35102

Lisbon, , Portugal

Site RO40004

Floreşti, Cluj, Romania

Site RO40001

Craiova, Dolj, Romania

Site RO40010

Craiova, Dolj, Romania

Site RO40007

Ploieşti, Prahova, Romania

Site RO40008

Timișoara, Timiș County, Romania

Site RO40012

Bucharest, , Romania

Site RO40006

Sibiu, , Romania

Site RU70012

Arkhangelsk, Arkhangelskaya oblast, Russia

Site RU70017

Ufa, Bashkortostan Republic, Russia

Site RU70009

Magnitogorsk, Chelyabinsk Oblast, Russia

Site RU70016

Nal'chik, Kabardino-Balkarskaya Respublika, Russia

Site RU70008

Pyatigorsk, Stavropol Kray, Russia

Site RU70001

Saint Petersburg, , Russia

Site SG65001

Singapore, Central Singapore, Singapore

Site SG65002

Singapore, Central Singapore, Singapore

Site KR82010

Busan Gwang'yeogsi, Busan Gwang'yeogsi, South Korea

Site KR82004

Suwon, Gyeonggi-do, South Korea

Site KR82016

Suwon, Gyeonggido [Kyonggi-do], South Korea

Site KR82017

Bundang, Gyeonggido, South Korea

Site KR82009

Jinju, Gyeongsangnam-do, South Korea

Site KR82003

Jeonju, Jeonrabugdo[Chollabuk-do], South Korea

Site KR82005

Cheongiu, North Chungcheong, South Korea

Site KR82002

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82001

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82013

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82007

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82008

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82006

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82015

Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], South Korea

Site KR82014

Seoul, Seoul Teugbyeolsi, South Korea

Site KR82011

Ulsan, Ulsan Gwang'yeogsi, South Korea

Site ES34003

Barcelona, Catalonia, Spain

Site ES34008

San Sebastian, Guipuzcoa, Guipúzcoa, Spain

Site ES34010

Málaga, Málaga, Spain

Site ES34006

Madrid, , Spain

Site ES34016

Madrid, , Spain

Site ES34004

Ourense, , Spain

Site ES34005

Seville, , Spain

Site ES34015

Valencia, , Spain

Site ES34017

Valencia, , Spain

Site ES34002

Valencia, , Spain

Site TW88605

Taichung, Taichung, Taiwan

Site TW88607

Taoyuan Hsien, Taoyuan, Taiwan

Site TW88606

Kaohsiung City, , Taiwan

Site TW88603

Taichung, , Taiwan

Site TW88601

Tainan City, , Taiwan

Site TW88604

Tainan City, , Taiwan

Site TW88608

Taipei, , Taiwan

Site TW88609

Taipei, , Taiwan

Site TW88611

Taipei, , Taiwan

Site TH66011

Chom Thong, Chiang Mai, Thailand

Site TH66001

Bangkok, Krung Thep Maha Nakhon [Bangkok], Thailand

Site TH66012

Bangkok, Krung Thep Maha Nakhon [Bangkok], Thailand

Site TH66002

Chiang Rai, , Thailand

Site TH66004

Khon Kaen, , Thailand

Site TH66006

Songkhla, , Thailand

Site UA38006

Chernivtsi, Chernivtsi Oblast, Ukraine

Site UA38001

Dnipropetrovsk, Dnipropetrovsk Oblast, Ukraine

Site UA38005

Kryvyi Rih, Dnipropetrovsk Oblast, Ukraine

Site UA38008

Ivano-Frankivsk, Ivano-Frankivsk Oblast, Ukraine

Site UA38004

Lviv, Lviv Oblast, Ukraine

Site UA38007

Lutsk, Volyn Oblast, Ukraine

Site UA38009

Uzhhorod, Zakarpattia Oblast, Ukraine

Site UA38003

Uzhhorod, Zakarpattia Oblast, Ukraine

Site GB44002

Middlesex, Hertfordshire, United Kingdom

Site GB44001

Liverpool, Wirral, United Kingdom

Site GB44003

Sheffield, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Chile; France; Germany; Hungary; Italy; Japan; Malaysia; Netherlands; Peru; Portugal; Romania; Russia; Singapore; South Korea; Spain; Taiwan; Thailand; Ukraine; United Kingdom

References

Kelly RJ, Shepherd FA, Krivoshik A, Jie F, Horn L. A phase III, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small-cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1127-1133. doi: 10.1093/annonc/mdz128.

Reference Type: DERIVED

PMID: 31070709 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=293

Link to results on the Astellas Clinical Study Results website

Other Identifiers

2015-002894-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8273-CL-0302

Identifier Type: -

Identifier Source: org_study_id