NCT04639219 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-03-23

This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Percentage of Participants Alive at 6 and 12 Months

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outcome · POSTED

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

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outcome · POSTED

Serum Concentrations of Deruxtecan (MAAA-1181a)

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outcome · POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Adults ≥18 years old. Other age restrictions may apply as per local regulations. * Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772\_A775dup / A775\_G776insYVMA, L755S, G778\_P780dup / P780\_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options. * Prior HER2 targeted therapy is permitted. * All patients must provide an FFPE tumor sample for retrospective central HER2 testing. * LVEF ≥50% * ECOG 0-1 * All patients have measurable target disease assessed by the Investigator based on RECIST v1.1 Exclusion Criteria: * HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. * HER2 mutant NSCLC. * Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke. * History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening * Corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG. * Lung-specific intercurrent clinically significant severe illnesses. * History of active primary immunodeficiency, known HIV, active HBV or HCV infection * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals * Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). * Has spinal cord compression or clinically active central nervous system metastases.
healthy Volunteers: false
maximum Age: 120 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
T-DXd monotherapy
intervention Names
Drug: Trastuzumab deruxtecan
label
T-DXd
type
EXPERIMENTAL

interventions

arm Group Labels
T-DXd
description
Trastuzumab deruxtecan (T-DXd) by intravenous infusion
name
Trastuzumab deruxtecan
other Names
DS-8201a (T-DXd)
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE
masking Description: None (open-label)

primary Purpose

TREATMENT

Enrollment

count: 102
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Confirmed ORR was defined as the percentage of participants who had a confirmed complete response (CR) or partial response (PR), as determined by ICR per RECIST v1.1. A CR was defined as disappearance of all target lesions (TLs) and PR was defined as at least a 30% decrease in the sum of the diameters (dms) of TL, taking as reference the baseline sum of diameters as long as criteria for PD were not met. An ICR of all radiological imaging data was carried out using RECIST v1.1. All images were collected centrally. The imaging scans were reviewed by 2 independent radiologists and were adjudicated, if required.
measure
Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)
time Frame
Tumor scans performed at screening,then every 6 weeks (q6w) +/- 1 week relative to 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)

secondary Outcomes

description
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.
measure
Duration of Response (DoR) as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
description
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.
measure
Disease Control Rate (DCR) as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
description
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.
measure
PFS as Per RECIST v1.1 Using ICR and Investigator Assessment
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)
description
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.
measure
Percentage of Participants Alive and Progression-Free at 6 and 12 Months as Per RECIST v1.1 Using ICR and Investigator Assessment
time Frame
At Months 6 and 12
description
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.
measure
Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment
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)
description
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.
measure
Overall Survival (OS)
time Frame
From the date of first treatment administration up to death, approximately 24 months
description
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.
measure
Percentage of Participants Alive at 6 and 12 Months
time Frame
At Months 6 and 12
description
Serum samples were collected at specified timepoints to determine serum concentrations of T-DXd and total anti-HER2 antibody.
measure
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)
description
Serum samples were collected at specified timepoints to determine serum concentrations of MAAA-1181a.
measure
Serum Concentrations of Deruxtecan (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)
description
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.
measure
Percentage of Participants With Anti-Drug Antibodies (ADA) to T-DXd
time Frame
Up to approximately 24 months

Full study description

brief Summary: This is an open-label, multi-center, single arm, Phase II study to evaluate the efficacy and safety of T-DXd for the treatment of unresectable and/or metastatic solid tumors harboring specific HER2 activating mutations regardless of tumor histology. The target population are patients who have progressed following prior treatment or who have no satisfactory alternative treatment options, including approved second line therapies in the specific tumor type. Pre-specified HER2 mutations will be locally assessed using NGS tests or alternative methods. Prior HER2 targeting therapy is permitted.

Source references

references

citation
Li BT, Meric-Bernstam F, Bardia A, Naito Y, Siena S, Aftimos P, Anderson I, Curigliano G, de Miguel M, Kalra M, Oh DY, Park JO, Postel-Vinay S, Rha SY, Satoh T, Spanggaard I, Michelini F, Smith A, Machado KK, Saura C; DESTINY-PanTumor01 study group. Trastuzumab deruxtecan in patients with solid tumours harbouring specific activating HER2 mutations (DESTINY-PanTumor01): an international, phase 2 study. Lancet Oncol. 2024 Jun;25(6):707-719. doi: 10.1016/S1470-2045(24)00140-2. Epub 2024 May 3.
pmid
38710187
type
DERIVED
citation
Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JA, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol. 2023 Oct;34(10):885-898. doi: 10.1016/j.annonc.2023.08.003. Epub 2023 Aug 18.
pmid
37597578
type
DERIVED