Non-Small Cell Lung CancerPhase 1TAS3351NCT05765734
A Study of TAS3351 in NSCLC Patients With EGFRmt
A Phase 1 study testing TAS3351 in people with Non-Small Cell Lung Cancer, run by Taiho Oncology, Inc. at 8 sites in 5 countries.
Trial summary
This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in participants with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- TAS3351
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 8 sitesin 5 countries
- Study dates
- 25 May 2023to 14 Mar 2025
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced, non-resectable or metastatic NSCLC
- Have adequate organ function
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- Has tumor tissue available to allow for analysis of EGFRmt status
- Dose Escalation:
- Has any EGFRmt status
Show all 9Show fewer
- Dose Escalation back-fill part, Dose Expansion and Phase II:
- Has any sensitizing EGFRmt and a confirmed C797S EGFRmt
- Has measurable disease per response evaluation criteria in solid tumors, version 1.1 (RECIST v1.1)
Who cannot join
- Participating in medical research not compatible with this study
- Symptomatic and unstable central nervous system (CNS) metastases
- Have not recovered from prior cancer treatment
- Have a significant cardiac condition
- Are a pregnant or breastfeeding female
- A serious illness or medical condition
- Unable to swallow or digest pills
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
United States3 sites
Next Oncology - Virginia
Fairfax, Virginia, 22031
University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology
Nashville, Tennessee, 37203
Japan2 sites
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
Shizuoka Cancer Center
Sunto-gun, Shizuoka, 411-8777
Germany1 site
Universitaetsklinikum Koeln
Cologne, North Rhine-Westphalia, 50937
About this study
Official title: A Phase 1/2 Study of TAS3351 in Patients With Advanced Non-Small Cell Lung Cancer and EGFR Mutations
This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in participants with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation.
Read the detailed description
This study will be conducted in 3 parts (i.e. dose escalation, dose expansion, and a phase 2 portion). The dose escalation part will investigate the safety and determine the recommended phase 2 dose and the recommended dosing regimen of TAS3351 administered orally. The dose expansion part will explore the efficacy of TAS3351 in NSCLC participants with C797S EGFR mutations. The phase 2 part will assess the efficacy of TAS3351 in NSCLC participants with C797S EGFR mutations.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- TAS3351
- Keywords
- Non-Small Cell Lung Cancer, NSCLC, EGFR mutation, C797S mutation, TAS3351
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAS3351Drug
Oral tablets.
| Study group | Role | What they receive |
|---|---|---|
| Part A1: Dose Escalation: 50 mg | Experimental | Participants received TAS3351 50 milligrams (mg), tablets, orally, once daily (QD), on Days 1-21 of each 21-day cycle, for maximum duration of 66 days. Receives: Drug: TAS3351 |
| Part A1: Dose Escalation: 100 mg | Experimental | Participants received TAS3351 100 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 126 days. Receives: Drug: TAS3351 |
| Part A1: Dose Escalation: 200 mg | Experimental | Participants received TAS3351 200 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 94 days. Receives: Drug: TAS3351 |
| Part A1: Dose Escalation: 350 mg | Experimental | Participants received TAS3351 350 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 46 days. Receives: Drug: TAS3351 |
| Part A1: Dose Escalation: 500 mg | Experimental | Participants received TAS3351 500 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 87 days. Receives: Drug: TAS3351 |
| Part A1: Dose Escalation: 700 mg | Experimental | Participants were to receive TAS3351 700 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle. Receives: Drug: TAS3351 |
| Part A2: Backfill | Experimental | Participants were to be enrolled in Part A2 (backfill) when a dose level in Part A1 was determined to be safe and preliminary antitumor activity was observed. Receives: Drug: TAS3351 |
| Part B: Dose Expansion | Experimental | .NSCLC participants with C797S EGFR mutations were planned for enrollment in Part B (dose expansion) and were to receive the recommended Phase 2 dose established in Part A. Receives: Drug: TAS3351 |
| Part C: Phase 2 | Experimental | NSCLC participants with C797S EGFR mutations were planned for enrollment in Part C (Phase 2) and were to receive the recommended Phase 2 dose established in Part A Receives: Drug: TAS3351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE)
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.
Measured: From first dose of the study drug up to 30 days after last dose (up to 21.7 months)
Part A1: Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
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.
Measured: Cycle 1 (cycle length = 21 days)
Part B: Dose Expansion: Percentage of Participants With Objective Response Rate (ORR) by Independent Central Review (ICR)
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).
Measured: Up to 21.7 months
Part C: Phase 2: Percentage of Participants With ORR by ICR
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.
Measured: Up to approximately 21.7 months
Secondary outcomes (28)
Part A1: Dose Escalation: Percentage of Participants With ORR
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.
Measured: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A1: Dose Escalation: Duration of Response (DoR)
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.
Measured: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A1: Dose Escalation: Percentage of Participants Exhibiting Disease Control Rate (DCR)
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.
Measured: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A2: Backfill: Number of Participants Exhibiting Progression Free Survival (PFS)
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.
Measured: From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)
Part A2: Backfill: Number of Participants Exhibiting Overall Survival (OS)
OS was measured from the date of first dose until the date of death due to any cause.
Measured: From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)
Part A1: Dose Escalation: Maximum Plasma Concentration (Cmax) of TAS3351
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Area Under The Plasma Concentration-Time Curve (AUC24) of TAS3351
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Area Under The Plasma Concentration-Time Curve (AUCinf) of TAS3351
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Time To Maximum Plasma Concentration (Tmax) of TAS3351
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Terminal Elimination Half-Life (T½) of TAS3351
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Cmax of Metabolite TAS-05-14317
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: AUC24 of Metabolite TAS-05-14317
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: AUCinf of Metabolite TAS-05-14317
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Tmax of Metabolite TAS-05-14317
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: T½ of Metabolite TAS-05-14317
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.
Measured: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part B: Dose Expansion and Part C: Phase 2: Number of Participants With TEAEs
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DoR by ICR
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: PFS by ICR
PFS is the time from date of first dose to the date of documentation of disease progression, or date of death, whichever occurs first.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DCR by ICR
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: ORR by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DoR by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: PFS by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DCR by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: Intracranial ORR (icORR) by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: Intracranial DoR (icDOR) by Investigator Assessment
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.
Measured: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: OS
OS was measured from the date of first dose until the date of death due to any cause.
Measured: Up to approximately 21.7 months
Part C: Phase 2: Participant Reported Outcome Assessed by European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
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.
Measured: Up to approximately 21.7 months
Part C: Phase 2: Participant Reported Outcome Assessed by EuroQol 5D-5L Questionnaire
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.
Measured: Up to approximately 21.7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start25 May 2023
- Primary completion14 Mar 2025
- Study completion14 Mar 2025
Why it stopped: Sponsor's decision, not based on safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05765734
- Sponsor's protocol ID
- 10073010
- Other IDs
- 2022-502595-23-00
- Acronym
- TAS3351
- Status last verified
- Feb 2026
- First submitted
- 8 Feb 2023
- Last updated
- 2 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of TAS3351 in Patients With Advanced Non-Small Cell Lung Cancer and EGFR Mutations
- ClinicalTrials.gov ID
- NCT05765734
- Acronym / sponsor ID
- TAS3351 / 10073010
- Conditions
- Non-Small Cell Lung Cancer
- Keywords
- Non-Small Cell Lung Cancer, NSCLC, EGFR mutation, C797S mutation, TAS3351
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's decision, not based on safety concerns
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 May 2023 (actual)
- Primary completion
- 14 Mar 2025 (actual)
- Study completion
- 14 Mar 2025 (actual)
- First posted
- 13 Mar 2023 (actual)
- Results
- Posted 2 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in participants with advanced or metastatic non-small cell lung cancer (NSCLC) harboring an acquired C797S epidermal growth factor receptor (EGFR) mutation.
Detailed description
This study will be conducted in 3 parts (i.e. dose escalation, dose expansion, and a phase 2 portion). The dose escalation part will investigate the safety and determine the recommended phase 2 dose and the recommended dosing regimen of TAS3351 administered orally. The dose expansion part will explore the efficacy of TAS3351 in NSCLC participants with C797S EGFR mutations. The phase 2 part will assess the efficacy of TAS3351 in NSCLC participants with C797S EGFR mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Part A1: Dose Escalation: 50 mg | Experimental | Drug: TAS3351Participants received TAS3351 50 milligrams (mg), tablets, orally, once daily (QD), on Days 1-21 of each 21-day cycle, for maximum duration of 66 days. |
| Part A1: Dose Escalation: 100 mg | Experimental | Drug: TAS3351Participants received TAS3351 100 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 126 days. |
| Part A1: Dose Escalation: 200 mg | Experimental | Drug: TAS3351Participants received TAS3351 200 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 94 days. |
| Part A1: Dose Escalation: 350 mg | Experimental | Drug: TAS3351Participants received TAS3351 350 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 46 days. |
| Part A1: Dose Escalation: 500 mg | Experimental | Drug: TAS3351Participants received TAS3351 500 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle, for a maximum duration of 87 days. |
| Part A1: Dose Escalation: 700 mg | Experimental | Drug: TAS3351Participants were to receive TAS3351 700 mg, tablets, orally, QD, on Days 1-21 of each 21-day cycle. |
| Part A2: Backfill | Experimental | Drug: TAS3351Participants were to be enrolled in Part A2 (backfill) when a dose level in Part A1 was determined to be safe and preliminary antitumor activity was observed. |
| Part B: Dose Expansion | Experimental | Drug: TAS3351.NSCLC participants with C797S EGFR mutations were planned for enrollment in Part B (dose expansion) and were to receive the recommended Phase 2 dose established in Part A. |
| Part C: Phase 2 | Experimental | Drug: TAS3351NSCLC participants with C797S EGFR mutations were planned for enrollment in Part C (Phase 2) and were to receive the recommended Phase 2 dose established in Part A |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Locally advanced, non-resectable or metastatic NSCLC
- Have adequate organ function
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- Has tumor tissue available to allow for analysis of EGFRmt status
- Has any EGFRmt status
Key exclusion criteria (7 listed)
- Participating in medical research not compatible with this study
- Symptomatic and unstable central nervous system (CNS) metastases
- Have not recovered from prior cancer treatment
- Have a significant cardiac condition
- Are a pregnant or breastfeeding female
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAS3351Oral tablets. | Drug | Part A1: Dose Escalation: 100 mg, Part A1: Dose Escalation: 200 mg, Part A1: Dose Escalation: 350 mg, Part A1: Dose Escalation: 50 mg, Part A1: Dose Escalation: 500 mg, Part A1: Dose Escalation: 700 mg, Part A2: Backfill, Part B: Dose Expansion, Part C: Phase 2 |
Primary outcome
Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE)
Time frame: From first dose of the study drug up to 30 days after last dose (up to 21.7 months)
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.
Part A1: Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (cycle length = 21 days)
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.
Part B: Dose Expansion: Percentage of Participants With Objective Response Rate (ORR) by Independent Central Review (ICR)
Time frame: Up to 21.7 months
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).
Part C: Phase 2: Percentage of Participants With ORR by ICR
Time frame: Up to approximately 21.7 months
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.
28 secondary outcomes
Part A1: Dose Escalation: Percentage of Participants With ORR
Time frame: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A1: Dose Escalation: Duration of Response (DoR)
Time frame: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A1: Dose Escalation: Percentage of Participants Exhibiting Disease Control Rate (DCR)
Time frame: From first dose of the study drug up to 30 days after the last dose (up to approximately 21.7 months)
Part A2: Backfill: Number of Participants Exhibiting Progression Free Survival (PFS)
Time frame: From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)
Part A2: Backfill: Number of Participants Exhibiting Overall Survival (OS)
Time frame: From first dose of the study drug up to 30 days after the last dose (up to 21.7 months)
Part A1: Dose Escalation: Maximum Plasma Concentration (Cmax) of TAS3351
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Area Under The Plasma Concentration-Time Curve (AUC24) of TAS3351
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Area Under The Plasma Concentration-Time Curve (AUCinf) of TAS3351
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Time To Maximum Plasma Concentration (Tmax) of TAS3351
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: Terminal Elimination Half-Life (T½) of TAS3351
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Cmax of Metabolite TAS-05-14317
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: AUC24 of Metabolite TAS-05-14317
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: AUCinf of Metabolite TAS-05-14317
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part A1: Dose Escalation: Tmax of Metabolite TAS-05-14317
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose; Cycle 1 Day 15: Pre-dose and at multiple timepoints up to 24 hours post dose
Part A1: Dose Escalation: T½ of Metabolite TAS-05-14317
Time frame: Cycle 1 Day -3: Pre-dose and at multiple timepoints up to 72 hours post dose
Part B: Dose Expansion and Part C: Phase 2: Number of Participants With TEAEs
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DoR by ICR
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: PFS by ICR
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DCR by ICR
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: ORR by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DoR by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: PFS by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: DCR by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: Intracranial ORR (icORR) by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: Intracranial DoR (icDOR) by Investigator Assessment
Time frame: Up to approximately 21.7 months
Part B: Dose Expansion and Part C: Phase 2: OS
Time frame: Up to approximately 21.7 months
Part C: Phase 2: Participant Reported Outcome Assessed by European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
Time frame: Up to approximately 21.7 months
Part C: Phase 2: Participant Reported Outcome Assessed by EuroQol 5D-5L Questionnaire
Time frame: Up to approximately 21.7 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TAS3351 in people with Non-Small Cell Lung Cancer, run by Taiho Oncology, Inc. at 8 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Japan, France, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE) (time frame: From first dose of the study drug up to 30 days after last dose (up to 21.7 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2026.