Breast Cancer, Glioblastoma, Non-small Cell Lung Cancer, Solid Tumor
Conditions
Brief summary
This is a first-in-human, open label, multicenter study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and the preliminary antitumor activity of TAS2940 in patients with advanced or metastatic solid tumors who are not candidates for approved or available therapies.
Detailed description
TAS2940 is a small molecule inhibitor of ERBB family proteins HER2 and EGFR. It has not been evaluated in human subjects yet. The study will be conducted in 2 parts, dose escalation and dose expansion. The dose escalation part will assess the safety and determine the maximum tolerated dose, the recommended phase 2 dose and the recommended dosing regimen of TAS2940 administered orally. The dose expansion part will assess preliminary anti-tumor activity in select solid tumors characterized by HER2 or EGFR aberrations.
Interventions
DRUGTAS2940
Study participants with solid tumors and EGFR or HER2 aberrations will receive TAS2940 tablets daily at increasing doses until MTD is reached.
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histologically confirmed solid cancer that is locally advanced and metastatic and available standard treatment options have been exhausted * Have adequate organ function * ECOG PS 0-1 Dose Escalation: * Have measurable or non- measurable disease per RECIST criteria v1.1 or RANO * Any solid tumor with EGFR and / or HER2 aberration Dose Expansion: * Have measurable disease per RECIST criteria v1.1 for solid tumor (excluding primary brain tumor) or RANO (for glioblastoma) * Cohort A: Non-small cell lung cancer (NSCLC) * Cohort B: HER2 positive breast cancer * Cohort C: Recurrent or refractory glioblastoma * Cohort D: Other solid tumors with EGFR or HER2 aberrations
Exclusion criteria
* Non-stable brain metastases * Have significant cardiovascular disorder * Have not recovered from prior cancer treatment * A serious illness or medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation:Maximum Tolerated Dose (MTD) | One Month | Determine the incidence of dose-liming toxicities (DLTs) and adverse events (AEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 within the first cycle |
| Dose Expansion:Overall Response Rate | 6 Months | Document the ORR, defined as proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR) based on investigator accessed radiographic response per RECIST 1.1 or RANO criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose Expansion:Incidence of treatment-emergent Adverse Events (Safety and tolerability) | Estimated up to 6 months | Safety and tolerability of TAS2940 based on reported AEs, graded according to NCI-CTCAE v.5.0 |
| Dose Expansion:Duration of Response (DOR) | Estimated up to 6 months | DOR, defined as time from the first documentation of response to date of objective tumor progression or death due to any cause, whichever occurs first. |
| Dose Escalation: Overall Response Rate (ORR) | 6 Months | Document the ORR defined as proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR) based on investigator accessed radiographic response per RECIST 1.1 or RANO criteria |
| Dose Expansion:Progression Free Survival (PFS) | Estimated up to 6 months | Date of PR or CR to date of objective progression or death due to any cause. |
| Dose Expansion:Pharmacokinetic profile of TAS2940 | 3 Months | Evaluation of the maximum observed plasma concentration; time to reach maximum concentration, area under the Concentration-time curve and time it takes for plasma concentration to fall by half its original value (T1/2) of TAS2940 |
| Dose Expansion:Disease Control Rate (DCR) | Estimated up to 6 months | DCR, defined as the proportion of patients experiencing a best overall response of Stable Disease (SD), PR or CR |
| Dose Escalation:Pharmacokinetic (PK) Profile | 3 Months | Evaluation of the maximum observed plasma concentration; time to reach maximum concentration, area under the Concentration-time curve and time it takes for plasma concentration to fall by half its original value (T1/2) of TAS2940 |
Countries
France, United States
Outcome results
None listed