Clinical Trial Radar

Part 1: Percentage of Participants Who Experience Dose-limiting Toxicities (DLTs)

A DLT is any of a prespecified list of adverse events (AEs) that occur during Cycle 1 (up to 21 days) if attributed to the study treatment and not attributed to any other clearly identifiable cause. The percentage of participants who experience DLTs will be reported. Each cycle is 21 days.

Cycle 1 (up to approximately 21 days); each cycle is 21 days

Part 1: Percentage of Participants Who Experience an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience AEs will be reported.

Up to approximately 5 years

Part 1: Percentage of Participants Who Discontinue Study Treatment Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.

Up to approximately 5 years

Part 1: Area Under the Curve (AUC) of total anti-HER3 antibody liquid chromatography-mass spectrometry (LC-MS) in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 1: AUC of anti-HER3 antibody-conjugated DXd (anti-HER3-ac-DXd) in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 1: AUC of DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 1: Maximum Concentration (Cmax) of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 1: Cmax of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 1: Cmax of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 1: Concentration Immediately Before the Next Dose is Administered (Ctrough) of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)

Part 1: Ctrough of anti-HER3-ac-DXd

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)

Part 1: Ctrough of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)

Part 1 and Part 2: Objective Response Rate (ORR)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by the investigator will be presented.

Up to approximately 5 years

Part 2: Percentage of Participants Who Experience an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience AEs will be reported.

Up to approximately 5 years

Part 2: Percentage of Participants Who Discontinue Study Treatment Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.

Up to approximately 5 years

Part 1 and Part 2: Disease Control Rate (DCR)

DCR is defined, per RECIST 1.1, as the percentage of participants who have a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD). SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm). Note: The appearance of one or more new lesions is also considered PD. The time from the first dose until the date of SD must be greater than or equal to 6 weeks. The DCR as assessed by the investigator will be presented.

Up to approximately 5 years

Part 1 and Part 2: Time to Response (TTR)

For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, TTR is defined as the time from the first dose to the first documented evidence of a CR or PR. The TTR as assessed by the investigator will be presented.

Up to approximately 5 years

Part 1 and Part 2: Duration of Response (DOR)

For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until PD or death. PD is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. DOR as assessed by the investigator will be presented.

Up to approximately 5 years

Part 1 and Part 2: Progression-free Survival (PFS)

PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by RECIST 1.1. PD is defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions is also considered PD. PFS as assessed by the investigator will be presented.

Up to approximately 5 years

Part 1 and Part 2: Overall Survival (OS)

OS is defined as time from first dose of study treatment to death due to any cause.

Up to approximately 5 years

Part 2: AUC of total anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 2: AUC of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 2: AUC of DXd in plasma

Blood samples will be collected at specified intervals for the determination of AUC.

At designated timepoints (up to approximately 5 years)

Part 2: Cmax of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 2: Cmax of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 2: Cmax of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Cmax.

At designated timepoints (up to approximately 5 years)

Part 2: Ctrough of anti-HER3 antibody LC-MS in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)

Part 2: Ctrough of anti-HER3-ac-DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)

Part 2: Ctrough of DXd in plasma

Blood samples will be collected at specified intervals for the determination of Ctrough.

At designated timepoints (up to approximately 5 years)