Trial Outcomes & Findings for A Study of TAS3351 in NSCLC Patients With EGFRmt (NCT NCT05765734)

Participants took part in the study from 25 May 2023 to 14 March 2025.

A total of 18 participants received at least one dose of TAS3351 in Part A1. The study was originally designed to be conducted in three parts: Phase 1: Part A (including Part A1: Dose Escalation and Part A2: Backfill) and Part B (Dose Expansion); Part C (Phase 2). However, as the study was terminated early, no participants were further enrolled in Parts A1 dose expansion for 700 milligrams (mg), A2, B, or C of the study and these parts were not conducted.

A Study of TAS3351 in NSCLC Patients With EGFRmt

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that started or worsened at the time of or after the first dose of study drug administration and within 30 days after the last dose of study drug and did not necessarily have a causal relationship to the use of the study drug.

DLTs were defined as adverse events (AEs) graded by Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0) assessed by the Investigator to be related to study treatment administration during Cycle 1 \& included:Hematologic Toxicity;grade 4 neutropenia greater than\[\>\]7days; febrile neutropenia (absolute neutrophil count \[ANC\] less than(\<)1000 per cubic millimeter (1000/mm3) with fever greater than or equal to(≥)38.3 degree celsius (°C) or fever ≥38.0°C for \> 1hour); grade 4 thrombocytopenia, Hepatic Toxicity: grade ≥3 total bilirubin \>7days; grade 4 total bilirubin; Renal Toxicity:creatinine clearance(CrCl)\<30 milliliters per minute (mL/min) for \> 3days despite supportive care;Other Nonhematologic Toxicity:grade ≥3 nonhematologic toxicity with: grade 3 nausea, vomiting, diarrhea, or hyperglycemia, prolonged delay (\>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Any death not clearly attributed to the underlying disease or extraneous causes.

ORR was the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1) criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (\<)10 millimeters (mm).

ORR was the proportion of participants experiencing a PR or CR according to RECIST v1.1 criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10mm.

ORR was the proportion of participants experiencing a best overall response of PR or CR according to RECIST v1.1 criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10mm.

DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm.

DCR was the proportion of participants who achieved a CR, PR, or stable disease (SD). Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis \<10 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study.

PFS was defined as the time from date of first dose to the date of documentation of disease progression, or date of death, whichever occurred first.

OS was measured from the date of first dose until the date of death due to any cause.

Cmax is the maximum observed plasma concentration within the dosing interval. Blood samples for pharmacokinetic (PK) analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

AUC24 is the area under the curve from the time of dosing up to time 24hours. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

AUCinf is the area under the plasma concentration-time curve from time of dosing extrapolated to infinity. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

Tmax is the time to maximum plasma concentration within the dosing interval. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

T1/2 is the terminal elimination half-life. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

Cmax is the maximum observed plasma concentration within the dosing interval. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

AUC24 is the area under the curve from the time of dosing up to time 24hours. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

AUCinf is the area under the plasma concentration-time curve from time of dosing extrapolated to infinity. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

Tmax is the time to maximum plasma concentration within the dosing interval. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

T1/2 is the terminal elimination half-life. Blood samples for PK analysis were collected at specified timepoints. A PK lead-in with a single TAS3351 dose on Cycle 1 Day -3, followed by PK sampling three days before the start of continuous daily dosing, was included to characterize the PK profile.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it did not necessarily have to have a causal relationship with this treatment. A TEAE was defined as an AE that is starting or worsening at the time of or after the first dose of study drug administration and within 30 days after the last dose of study drug and did not necessarily have a causal relationship to the use of the study drug.

DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm.

PFS is the time from date of first dose to the date of documentation of disease progression, or date of death, whichever occurs first.

DCR was the proportion of participants who achieved a CR, PR, or SD. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis \<10 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study.

ORR was the proportion of participants experiencing a PR or CR according to RECIST v1.1 criteria. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10mm.

DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm.

PFS was defined as the time from date of first dose to the date of documentation of disease progression, or date of death, whichever occurred first.

DCR was the proportion of participants who achieved a CR, PR, or SD. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis \<10 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study.

The icORR was defined as percentage of participants experiencing a PR or CR. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10mm. The icORR was planned to be assessed based on ORR of central nerve system (CNS) lesions only.

The icDoR was planned to be calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to \<10 mm. The icDoR was planned to be assessed based on DoR of CNS lesions only.

OS was measured from the date of first dose until the date of death due to any cause.

The EORTC QLQ-C30 is a 30-item questionnaire meant to assess different aspects that define the quality of life of cancer participants and survivors. It facilitates insights into participants' physical, emotional, and social wellbeing, ultimately supporting more informed treatment decisions and care strategies. The questionnaire is divided into 4 parts, namely global health status/ quality of life, functional scales, symptom scales and single-item symptoms. Each item was meant to be scored on a scale of 1 (Not at all) to 4 (Very much). Scores obtained from each section are transformed to a 0-100 score. For the functional and global health status scales, higher scores indicate better functioning or quality of life. For symptom scales and single-item measures, higher scores indicate greater symptom severity.

The EQ-5D-5L is a standardized, generic, participant-reported instrument developed by the EuroQol Group to assess health-related quality of life across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Participants were to rate five dimensions namely, mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item is scores on a score of 1 (no problems) to 5 (extreme problems). The combination of responses forms a 5-digit health state which is converted into a single utility index score using a country-specific value set. Higher utility scores indicate better health-related quality of life.