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TAK-931 80 milligram (mg), PIC, orally, once on Day 1 Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, tablet, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until progressive disease (PD), or unacceptable toxicity or any treatment discontinuation is determined.

TAK-931 80 mg, tablet, orally, once on Day 1 of Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, PIC, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.

TAK-931 tablet, orally, once under fed state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fasted state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.

TAK-931 tablet, orally, once under fasted state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fed state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.

TAK-931 PIC

TAK-931 Tablet

Medical Director

The purpose of this study is to estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet.

The drug being tested in this study is called TAK-931. TAK 931 is being tested to treat participants who have advanced solid tumors. This study will look at relative bioavailability, effect of food and gastric pH modification on the PK of TAK-931.

The study will enroll approximately 44 participants. The study will be conducted in 2 parts: Part 1 and Part 2. In Part 1 and Part 2, participants will be randomly assigned (by chance, like flipping a coin) in a crossover design. In Part 1, participants will be assigned to 1 of the 2 following treatment sequences:

* TAK-931 80 mg PIC + TAK-931 80 mg Tablet
* TAK-931 80 mg Tablet + TAK-931 80 mg PIC

Part 2 of the study will be initiated, once the preliminary PK data from Part 1 is available to determine the relative bioavailability of the tablet formulation in reference to PIC and to calculate the single dose of TAK-931 tablet to be used in Part 2.In Part 2, participants will be assigned to 1 of the 2 following treatment sequences:

* TAK-931 TBD Fed + TAK-931 TBD Fasted
* TAK-931 TBD Fasted + TAK-931 TBD Fed

This multi-center trial will be conducted in the Netherlands. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic and will be contacted for approximately 30 days after receiving their last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first for a follow up assessment.

A Study to Assess the Relative Bioavailability, Effect of Food, and Gastric Potential Hydrogen (pH) Modification on the Pharmacokinetics (PK) of TAK-931 in Participants With Advanced Solid Tumors

A Phase 1, Open-Label Study to Assess the Relative Bioavailability, Effect of Food, and Gastric pH Modification on the Pharmacokinetics of TAK-931 in Patients With Advanced Solid Tumors

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

ORR was defined as the percentage of participants achieving complete response (CR) and partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD.

PFS was defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occured first. Per RECIST V1.1, PD was defined as at least a 20% increase in the SoD (Sum of Diameters) of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 millimeter (mm).

DCR was defined as the percentage of participants with CR, PR plus stable disease (SD) greater than or equal to (\>=) 1 post baseline computed tomography (CT) scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR was defined as disappearance of all lesions. PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

DOR was defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR was defined as disappearance of all lesions, PR was defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD was defined as at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm.

An AE was defined as any untoward medical occurrence in a participant who has enrolled in a study; it does not necessarily have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) was defined as an adverse event with an onset that occurs after receiving study drug. A severity grade was defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. As per NCI-CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE.

Millennium Pharmaceuticals, Inc.

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. As planned, safety data was collected and analyzed as per sequence and in accordance with the study design.

TAK-931 80 mg, PIC, orally, once on Day 1, followed by TAK-931 80 mg tablet, orally, once on Day 3, further followed by TAK-931 50 mg PIC, orally, once daily from Days 5 to 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles, until PD, or unacceptable toxicity or any treatment discontinuation is determined.

Part 1, Sequence A: TAK-931 80 mg PIC + TAK-931 80 mg Tablet

TAK-931 80 mg, tablet, orally, once on Day 1, followed by TAK-931 80 mg PIC, orally, once on Day 3, further followed by TAK-931 50 mg PIC, orally, once daily from Day 5 to Day 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.

Part 1, Sequence B: TAK-931 80 mg Tablet + TAK-931 80 mg PIC

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Netherlands

Region of Enrollment

Body Mass Index (BMI)

The safety set included all participants who received any amount of study drug.

Following log-transformation, PK parameters were analyzed by analysis of variance (ANOVA) fitting terms for treatment group, sequence and period. Participants within sequence were treated as a random effect. The obtained point estimates and adjusted 90 percent (%) confidence intervals (CIs) for difference in treatment were exponentially back transformed to provide point and confidence interval estimates for the ratios of interest appropriately.

TAK-931 80 mg, PIC, orally, once, on Day 1 or Day 3 of Cycle 0, further followed by TAK-931 50 mg PIC, orally, once daily from Day 5 to Day 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.

TAK-931 80 mg PIC

TAK-931 80 mg, tablet, orally, once, on Day 1 or Day 3 of Cycle 0, further followed by TAK-931 50 mg PIC, orally, once daily from Day 5 to Day 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.

TAK-931 80 mg Tablet

The pharmacokinetic (PK) set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.

Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC

Following log-transformation, PK parameters were analyzed by ANOVA fitting terms for treatment group, sequence and period. Participants within sequence were treated as a random effect. The obtained point estimates and adjusted 90% CIs for difference in treatment were exponentially back transformed to provide point and confidence interval estimates for the ratios of interest appropriately.

The PK set included all participants who completed the protocol-specified dosing and had sufficient plasma TAK-931 concentration-time data to reliably estimate the PK parameter.

Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC

Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC

Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets

Part 1, CL/F: Oral Clearance for TAK-931

Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931

The response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 postbaseline response. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.

Part 1: Overall Response Rate (ORR)

The safety set included all participants who received any amount of study drug. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.

Part 1: Progression-free Survival (PFS)

Part 1: Disease Control Rate (DCR)

The response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and had at least 1 postbaseline response. Here overall number of participants "N" are those who had CR or PR. As planned, efficacy data was collected and analyzed as per sequence and in accordance with the study design.

Part 1: Duration of Response (DOR)

SAEs

TEAEs

TEAEs Leading to Discontinuation or Dose Modification

The safety set included all participants who received any amount of study drug. As planned, safety data was collected and analyzed as per sequence and in accordance with the study design.

Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification

Part 1: Percentage of Participants With Grade 3 or Higher TEAEs

Eosinophils: Grade 0 to Grade 0

Eosinophils: Grade 0 to Grade 1

Eosinophils: Grade 1 to Grade 0

Hemoglobin: Grade 0 to Grade 0

Hemoglobin: Grade 0 to Grade 1

Hemoglobin: Grade 1 to Grade 0

Hemoglobin: Grade 1 to Grade 1

Hemoglobin: Grade 1 to Grade 2

Hemoglobin: Grade 1 to Grade 3

Hemoglobin: Grade 2 to Grade 2

Leukocytes: Grade 0 to Grade 0

Leukocytes: Grade 0 to Grade 1

Leukocytes: Grade 0 to Grade 2

Leukocytes: Grade 0 to Grade 3

Lymphocytes: Grade 0 to Grade 0

Lymphocytes: Grade 0 to Grade 1

Lymphocytes: Grade 0 to Grade 2

Lymphocytes: Grade 0 to Grade 3

Lymphocytes: Grade 1 to Grade 1

Lymphocytes: Grade 1 to Grade 2

Lymphocytes: Grade 2 to Grade 2

Lymphocytes: Grade 3 to Grade 2

Neutrophils: Grade 0 to Grade 0

Neutrophils: Grade 0 to Grade 2

Neutrophils: Grade 0 to Grade 3

Neutrophils: Grade 0 to Grade 4

Platelets: Grade 0 to Grade 0

Platelets: Grade 0 to Grade 1

Platelets: Grade 1 to Grade 1

Alanine Aminotransferase: Grade 0 to Grade 0

Alanine Aminotransferase: Grade 0 to Grade 1

Alanine Aminotransferase: Grade 1 to Grade 0

Alanine Aminotransferase: Grade 1 to Grade 1

Alkaline Phosphatase: Grade 0 to Grade 0

Alkaline Phosphatase: Grade 0 to Grade 1

Alkaline Phosphatase: Grade 1 to Grade 0

Alkaline Phosphatase: Grade 2 to Grade 0

Alkaline Phosphatase: Grade 3 to Grade 0

Aspartate Aminotransferase: Grade 0 to Grade 0

Aspartate Aminotransferase: Grade 0 to Grade 1

Aspartate Aminotransferase: Grade 1 to Grade 0

Aspartate Aminotransferase: Grade 1 to Grade 1

Aspartate Aminotransferase: Grade 2 to Grade 0

Bilirubin: Grade 0 to Grade 0

Bilirubin: Grade 0 to Grade 1

Creatinine: Grade 0 to Grade 0

Creatinine: Grade 0 to Grade 1

Creatinine: Grade 0 to Grade 2

Creatinine: Grade 1 to Grade 1

Glucose: Grade 0 to Grade 0

Magnesium: Grade 0 to Grade 0

Magnesium: Grade 0 to Grade 1

Magnesium: Grade 1 to Grade 1

Potassium: Grade 0 to Grade 0

Potassium: Grade 0 to Grade 1

Potassium: Grade 0 to Grade 3

Potassium: Grade 1 to Grade 1

Sodium: Grade 0 to Grade 0

Sodium: Grade 0 to Grade 1

Sodium: Grade 1 to Grade 0

Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters

TAK-931 80 milligram (mg), powder in capsule (PIC), orally, once on Day 1, followed by TAK-931 80 mg tablet, orally, once on Day 3, further followed by TAK-931 50 mg PIC, orally, once daily from Days 5 to 16 in Cycle 0 (16-day treatment cycle), followed by a 7-day rest period, further followed by TAK-931 50 mg PIC, orally, once daily for up to 14 days in Cycle 1, followed by a 7-day rest period in 21-day treatment cycles, until progressive disease (PD), or unacceptable toxicity or any treatment discontinuation is determined.

Spots Global Cancer Trial Database for neoplasms, advanced solid