Phase 2
Completed N=101
A Study to Evaluate the Safety, Tolerability, and Activity of TAK-931 in Participants With Metastatic Pancreatic Cancer, Metastatic Colorectal Cancer, and Other Advanced Solid Tumors
Source: ClinicalTrials.gov NCT03261947 ↗Enrolled (actual)
101
Serious AEs
28.7%
Results posted
Sep 2021
Primary outcomePrimary: Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort — 50 percentage of participants
Summary
The purpose of this study is to confirm the safety and tolerability of TAK-931 in a cohort of Western participants with metastatic solid tumors and to evaluate the anti-tumor activity of TAK-931 in participants with metastatic pancreatic cancer, colorectal cancer (CRC), squamous esophageal cancer (sqEC), and squamous non-small-cell lung cancer (sqNSCLC).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Dose Limiting Toxicities (DLTs) in Western Safety Cohort |
50 | — |
| PRIMARY Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), TEAEs Leading to Dose Modifications and TEAEs Leading to Treatment Discontinuation in Western Safety Cohort |
100; 58.3; 33.3; 8.3 | — |
| PRIMARY Disease Control Rate (DCR) in Tumor-Specific Cohorts |
46.2; 51.6; 52.6; 58.8 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for TAK-931 |
173.61; 204.69; 185.46; 196.17; 180.55; 216.18 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 |
1.57; 2.00; 1.85; 1.59; 2.00; 1.97 | — |
| SECONDARY AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 |
1190.22; 1166.40; 1302.40; 1475.88; 1290.72; 1542.82 | — |
| SECONDARY AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 |
1165.52; 1114.23; 1311.41; 1426.70; 1289.33; 1551.57 | — |
| SECONDARY CLr: Renal Clearance of TAK-931 |
2.16 | — |
| SECONDARY t1/2z: Terminal Disposition Phase Half-life for TAK-931 |
5.95; 5.53; 6.18 | — |
| SECONDARY CLss/F: Steady-state Apparent Oral Clearance for TAK-931 |
39.71; 45.58; 35.57 | — |
| SECONDARY Rac(AUC): Accumulation Ratio Based on AUC Over the Dosing Interval (AUCτ) for TAK-931 |
1.27; 1.10; 1.12 | — |
| SECONDARY Overall Response Rate (CR and PR) |
8.3; 0; 0; 5.3; 0 | — |
| SECONDARY Duration of Response (DOR) |
NA; NA | — |
| SECONDARY Progression Free Survival (PFS) |
2.05; 1.31; 1.45; 3.02; 2.12 | — |
| SECONDARY Overall Survival (OS) in the Tumor-Specific Cohorts |
4.67; 7.72; 8.61; NA | — |
| SECONDARY Percentage of Participants With Grade >=3 TEAEs, SAEs, TEAEs Leading to Dose Modifications, and TEAEs Leading to Treatment Discontinuation in Tumor-Specific Cohorts |
73.3; 54.3; 57.1; 44.4; 40.0; 22.9 | — |
| SECONDARY Percentage of Participants With Clinically Significant Changes in Laboratory Values, Reported as Adverse Events in Tumor-Specific Cohorts |
26.7; 17.1; 38.1; 27.8; 20.0; 8.6 | — |
| SECONDARY Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements, Reported as Adverse Events in Tumor-Specific Cohorts |
0; 2.9; 0; 0; 0; 5.7 | — |
Eligibility Criteria
Inclusion Criteria
- Adult male or female participants aged >=20 years (Japan) or >=18 years (United States).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Has pathologically confirmed metastatic pancreatic adenocarcinoma that has progressed after, at least, a first line of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed metastatic adenocarcinoma of the colon or rectum who have progressed to at least 2 lines of standard systemic chemotherapy for the metastatic disease, OR participants with pathologically confirmed locally advanced or metastatic sqEC that has progressed after at least a first line of standard systemic therapy for metastatic disease. First-line participants can be enrolled if a platinum doublet is contraindicated or refused by the participants, OR pathologically confirmed locally advanced or metastatic sqNSCLC that has progressed after at least 2 lines of standard systemic therapy for metastatic disease.
- For the Western safety cohort only: participants with locally advanced or metastatic solid tumor for whom no standard treatment with an established survival benefit is available or if the participant refuses other standard therapy.
- For disease-specific cohort participants: measurable disease per RECIST v. 1.1
- Left ventricular ejection fraction greater than (>) 50% as measured by ECHO or MUGA scan within 4 weeks before receiving the first dose of study drug.
- Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy).
- Suitable venous access for the study-required blood sampling.
- For the Western safety cohort only: willingness to undergo serial skin tissue biopsies.
- For disease-specific cohort participants: Must have an archival (banked) tumor sample or agree to have a new (fresh) tumor biopsy during the screening period. If a new tumor sample is needed, the disease should be accessible for a nonsignificant risk biopsy procedure (those occurring outside the brain, lung/mediastinum, and pancreas, or obtained with endoscopic procedures not extending beyond the stomach or bowel). For participants in the Western safety cohort, this biopsy is optional.
Exclusion Criteria
- Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.
- Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin, rifapentine, or Saint John's wort within 14 days before the first dose of study drug.
- Treatment with any systemic anticancer treatment (including investigational products) within 30 days or 5 half-lives, whichever is shorter, before the first dose of study drug.
- History of any of the following within the last 3 months before administration of the first dose of study drug:
- Ischemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease.
- Ischemic cerebrovascular event, including transient ischemic attack and artery, revascularization procedures.
- Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
- New York Heart Association Class III to IV heart failure.
- Any other cardiac condition that, in the opinion of the investigator, could pose an additional risk for participation in the study (example, pericardial effusion or restrictive cardiomyopathy).
- Baseline prolongation of the QT interval corrected for heart rate (HR) using Fridericia's formula [QT interval corrected for heart rate using Fridericia's formula (QTcF); example, repeated demonstration of QTcF interval >480 millisecond (ms), history of congenital long QT syndrome, or torsades de pointes].
- Hypertens
Data sourced from ClinicalTrials.gov (NCT03261947). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.