Trastuzumab Deruxtecan in Participants With HER2-overexpressing Advanced or Metastatic Colorectal Cancer

Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Confirmed objective response rate (ORR), defined as the number (percentage) of participants with complete response (CR) or partial response (PR), were assessed by Investigator assessment based on RECIST version 1.1. CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. ORR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

DoR, defined as time from the initial response (CR or PR) by BICR and Investigator assessment until documented tumor progression or death from any cause. DoR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Disease Control Rate (DCR), defined as the proportion of subjects who achieved CR, PR, or SD for a minimum of 6 weeks during study treatment; DCR based on BICR and DCR based on Investigator assessments assessed according to RECIST version 1.1. DCR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Clinical Benefit Rate (CBR), defined as proportion of subjects who achieved CR, PR, or SD for at least 6 months; CBR based on BICR and CBR based on Investigator assessments will both be determined based on RECIST version 1.1. CBR was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Progression Free Survival (PFS) defined as the time from date of randomization/registration until first objective radiographic tumor progression or death from any cause, based on BICR and Investigator assessment according to RECIST version 1.1. PFS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Overall Survival (OS) defined as the time from date of randomization/ registration until death from any cause, according to RECIST version 1.1. OS was assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

A Treatment-emergent Adverse Events (TEAE) is defined as an AE that occurs, having been absent before the first dose of study drug or has worsened in severity or seriousness after initiating the study drug until 47 days after the last dose of the study drug. Serious AEs with an onset or worsening 48 days or more after the last dose of study drug, if considered related to study treatment. are also TEAEs. TEAEs were assessed in the Safety Analysis Set at data cut-off date of 01 Nov 2022.

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Descriptive statistics will be provided for serum concentration data of T-DXd, DXd, and total anti-HER2 antibody. Serum concentrations were assessed in the Pharmacokinetics Analysis Set at data cut-off date of 01 Nov 2022.

Immunogenicity will be assessed through characterization of incidence and titer of Anti-drug Antibodies (ADAs), the number and percentage of subjects positive for NAb of T-DXd by dose level will also be determined. ADAs and NAbs were assessed in the Immunogenicity Analysis Set at data cut-off date of 01 Nov 2022.

Exploratory outcome, results not included in this submission. The QLQ-C30 is composed of both multi-item scales and single-item measures. These include 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Each of the multi-item scales includes a different set of items and no item occurs in more than 1 scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Patient questionnaires were assessed in the Full Analysis Set at data cut-off date of 01 Nov 2022.

Exploratory outcome, results not included in this submission. EORTC QLQ-CR29 is designed to be administered in addition to EORTC QLQ-C30. The EORTC QLQ-CR29 is a specific questionnaire for Colorectal Cancer. Scale from 0 to 100, A higher scale represents better function and a higher quality of life.

Exploratory outcome, results not included in this submission. The EQ-5D-5L is self-administered and consists of 2 parts, the EQ-5D-5L descriptive system and the EQ-visual analogue scale. On each dimension, a score of 1 indicates no patient problems in that dimension, 2 indicates slight problems in that dimension, 3 indicates moderate problems in that dimension, 4 indicates severe problems in that dimension and 5 indicates extreme problems in that dimension.

Exploratory outcome, results not included in this submission. The PGI-TT item is included to assess how a patient perceives the overall tolerability of the study treatment over the past 7 days. This is a single-item questionnaire, and patients will rate the bother associated with any treatment-related symptoms using response options ranging from "Not at all" to "Very much".

Exploratory outcome, results not included in this submission. The PGIS item is included to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. This is a single-item questionnaire, and patients will choose the response that best describes the severity of their overall cancer symptoms with options ranging from "No Symptoms" to "Very Severe".

Exploratory outcome, results not included in this submission. The PGIC item is included to assess how a patient perceives their overall change in health status since the start of study treatment. This is a single-item questionnaire, and patients will choose from response options ranging from "Much Better" to "Much Worse".

Exploratory outcome, results not included in this submission. The impact of treatment and disease on healthcare resource use (including inpatient admissions, intensive care unit admissions, and length of stay in hospital) will be captured/collected in this study on an event-driven basis.