Following recommendation by SOLAR Study IDMC, Astellas closed enrollment in ASP8273 studies.

Purpose of the study is to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

• the safety and tolerability of ASP8273.
• the pharmacokinetics (PK) of ASP8273.
• the antitumor activity of ASP8273.

This study consists of Phase I and Phase II.

The objectives of Phase I are to determine the following in patients with non-small cell lung cancer (NSCLC) harboring EGFR activating mutations.

• safety and tolerability of ASP8273.
• the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of ASP8273 based on the dose limiting toxicity (DLT) profile.
• pharmacokinetics (PK) of ASP8273.
• antitumor activity of ASP8273.

The objectives of Phase II are to determine the following at the RP2D of ASP8273 in patients with NSCLC harboring EGFR mutation.

• efficacy of ASP8273
• safety of ASP8273
• PK of ASP8273

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of NSCLC.

• Patients confirmed to have the del ex19, L858R, G719X, or L861Q mutation among the EGFR activating mutations (patients at the study site who are documented to have any of the above-stated EGFR activating mutations can be enrolled in the study).

• Life expectancy ≥ 12 weeks based on the investigator's/subinvestigator's judgment.

• [Phase I]

  • Patients who have previously been treated with EGFR tyrosine-kinase inhibitors (EGFR-TKIs)*
  • Those who are not expected to show a therapeutic response to existing treatments in the investigator's/subinvestigator's opinion.

• [Phase II]

  • Patients who have been confirmed to have progressive disease (PD) after previous treatment with EGFR-TKIs*; for those who have received 2 or more regimens of previous treatment, the last regimen before enrollment should have included EGFR-TKIs.
  • *Erlotinib, gefitinib, and EGFR-TKIs under clinical investigation (e.g., neratinib, afatinib, dacomitinib)
  • Expression of the EGFR-T790M mutation as confirmed by a tumor biopsy of the primary or metastatic lesions after confirmation of PD following previous treatment with EGFR-TKIs and before enrollment, or by a tumor tissue sample that had been collected and archived after confirmation of PD following previous treatment with EGFR-TKIs.
  • At least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

Exclusion Criteria:

• Persistent clinical evidence of previous antitumor treatment related toxicity ≥ Grade 2 using the Japan Clinical Oncology Group (JCOG) Japanese translation of the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (NCI CTCAE v4.0 - JCOG) (except alopecia and skin toxicities considered irrelevant in study enrollment by the investigator/sub-investigator).
• History of or concurrent interstitial lung disease
• Received treatment with a reversible EGFR-TKI (erlotinib or gefitinib) within 8 days before the start of the study treatment.
• Received previous treatment (except reversible EGFR-TKIs) intended to have antitumor effects or treatment with another investigational drug or an investigational device within 14 days before the start of the study treatment.
• Previously received treatment with EGFR-TKIs (e.g., CO-1686, AZD9291) that can inhibit EGFR with the T790M mutation.
• It is planned that the subject will undergo a surgical procedure during the course of the study or the subject still has an unhealed wound after previous surgery
• Symptomatic central nervous system (CNS) lesions.

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.