An Open-label, Randomized Phase 3 Efficacy 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
Overview
- Phase
- Phase 3
- Intervention
- naquotinib mesilate
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Sponsor
- Astellas Pharma Global Development, Inc.
- Enrollment
- 530
- Locations
- 167
- Primary Endpoint
- Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Investigators
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 ≤
- •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.
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.
Arms & Interventions
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).
Intervention: naquotinib mesilate
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).
Intervention: Erlotinib
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).
Intervention: Gefitinib
Outcomes
Primary Outcomes
Progression Free Survival (PFS) as Assessed by Independent Radiologic Review (IRR)
Time Frame: From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months)
PFS was defined as the time from the date of randomization until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by IRR. Results are based Kaplan-Meier estimate. If a participant had neither progressed nor died, who received any further anticancer therapy for the disease before radiological progression, the participant was censored at the date of last radiological assessment. If progression or death occurred after missing 2 scheduled radiological assessments, the participant was censored at the date of last radiological assessment or at the date of randomization if no post-baseline radiological assessment was available.
Secondary Outcomes
- Percentage of Deaths(From date of randomization up to data cut-off date 21 Dec 2017 (approximately 22 months))
- European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC-QLQ-C30)(Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months))
- Percentage of Participants With Objective Response (OR)(From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months))
- PFS as Assessed by the Investigator(From date of randomization up to data cut-off date 09 May 2017 (approximately 15 months))
- Percentage of Participants With Disease Control(From date of first dose of study drug up to data cut-off date 09 May 2017 (approximately 15 months))
- Duration of Response (DOR)(From date of first response up to data cut-off date 09 May 2017 (approximately 15 months))
- Number of Participants With Adverse Events (AEs)(From first dose of study drug up to 30 days after last dose of study drug taken up to data cut-off 09 May 2017)
- Functional Assessment of Cancer Therapy - EGFR Inhibitors Subscale (FACT-EGFRI-18) Questionnaire(Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months))
- European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC-QLQ-LC13)(Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months))
- EuroQol 5-Dimension 5-Level Questionnaire (EQ-5D-5L)(Day 1 of each cycle up to data cut off 09 May 2017 (approximately 15 months))