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Phase 2 Completed N=101 Treatment

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

OutcomeResultp-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
View full record on ClinicalTrials.gov →

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.

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