A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations

Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment

DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression (date of progression-free survival \[PFS\] event or censoring - date of first response + 1). The DoR was calculated using Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)

Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment

DCR at 6 weeks was defined as the percentage of participants who had the best objective response (BoR) of confirmed CR or PR, or who had stable disease (SD) (without subsequent cancer therapy), for at least 5 weeks after first dose of study treatment. DCR at 12 weeks was defined as the percentage of patients who had the BoR of confirmed CR or PR, or who had SD (without subsequent cancer therapy), for at least 11 weeks after first dose of study treatment. CR was defined as disappearance of all TL and PR was defined as at least a 30% decrease in sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (\>=20% increase in sum of dms of TLs and an absolute increase of \>=5 millimeters, taking as reference smallest sum of dms since treatment started including baseline sum of dms). CI was calculated using Clopper-Pearson method.

Time frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)

PFS as Per RECIST v1.1 Using ICR and Investigator Assessment

PFS was defined as the time from first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from assigned therapy or received another anti-cancer therapy prior to progression (i.e. date of PFS event or censoring - date of first dose + 1). PFS was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.

Time frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)

Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment

Percentage of participants alive and progression-free at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.

Time frame: At Months 6 and 12

Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment

Confirmed ORR was defined as the percentage of participants who had a confirmed CR or PR as determined by investigator per RECIST v1.1. A CR was defined as disappearance of all TLs and PR was defined as \>=30% decrease in the sum of the dms of TL, taking as reference the baseline sum of dms as long as criteria for PD were not met.

Time frame: Tumor scans performed at screening, then q6w +/- 1 week relative to the date of first treatment administration until RECIST v1.1 objective PD, withdrawal of consent, or death by any cause, up to DCO date of 25 Jan 2023 (approximately 24 months)

Overall Survival (OS)

OS was defined as the time from the date of first dose of study treatment administration until death due to any cause regardless of whether the patient withdrew from therapy or received another anti-cancer therapy (i.e. date of death or censoring - date of first dose + 1). OS was calculated using the Kaplan-Meier technique. CI for median OS derived based on the Brookmeyer-Crowley method.

Time frame: From the date of first treatment administration up to death, approximately 24 months

Percentage of Participants Alive at 6 and 12 Months

Percentage of participants alive at 6 and 12 months are reported. It was calculated using the Kaplan-Meier technique. CI for median PFS derived based on the Brookmeyer-Crowley method.

Time frame: At Months 6 and 12

Serum Concentrations of T-DXd and Total Anti-HER2 Antibody

Serum samples were collected at specified timepoints to determine serum concentrations of T-DXd and total anti-HER2 antibody.

Time frame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)

Serum Concentrations of Deruxtecan (MAAA-1181a)

Serum samples were collected at specified timepoints to determine serum concentrations of MAAA-1181a.

Time frame: Pre-infusion and 15 minutes post-infusion in Cycles 1, 2 and 4 and 5 hours post-infusion in Cycle 1 (each cycle 21 days)

Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd

Blood samples were collected to evaluate the presence of ADAs for T-DXd using validated assays. ADA prevalence was defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence was defined as the percentage of participants who were evaluable for ADA and were treatment-emergent ADA-positive. Treatment-emergent ADA was defined as either treatment-induced (baseline ADA negative, post-baseline ADA positive) or treatment-boosted ADA. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted to \>=2 fold during the study period. Persistently positive was defined as \>=2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive was defined as having \>=1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Time frame: Up to approximately 24 months