A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations (DPT01)

A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd) for the Treatment of Unresectable and/or Metastatic Solid Tumors Harboring HER2 Activating Mutations Regardless of Tumor Histology

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast
• Intervention / Treatment: Drug: Trastuzumab deruxtecan

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Anderlecht, Belgium, 1070
    • Research Site
• Canada
  • CA
    • Toronto, CA, Canada, M5G 2M9
      • Research Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Research Site
• France
  • Bordeaux, France, 33076
    • Research Site
  • Lyon, France, 69008
    • Research Site
  • Villejuif, France, 94805
    • Research Site
• Italy
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20162
    • Research Site
  • Naples, Italy, 80131
    • Research Site
• Japan
  • Chūōku, Japan, 104-0045
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Suita-shi, Japan, 565-0871
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• United States
  • California
    • Santa Rosa, California, United States, 95403
      • Research Site
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New Jersey
    • Middletown, New Jersey, United States, 07748
      • Research Site
  • New York
    • Commack, New York, United States, 11725
      • Research Site
    • Harrison, New York, United States, 10604
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: T-DXd; T-DXd monotherapy	Drug: Trastuzumab deruxtecan; Trastuzumab deruxtecan (T-DXd) by intravenous infusion; Other Names: DS-8201a (T-DXd)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Overall Response Rate (ORR) as Per RECIST v1.1 Using Independent Central Review (ICR)	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Daiichi Sankyo Co., Ltd.

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Redacted CSR synopsis
• Redacted SAP
• Redacted CSP

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2020
• Primary Completion (Actual): January 25, 2023
• Study Completion (Estimated): July 14, 2026

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HER2; Metastatic; Solid Tumors; DS-8201a; T-DXd; Trastuzumab Deruxtecan; Histology Agnostic
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; trastuzumab deruxtecan
• Other Study ID Numbers: D967MC00001; 2020-002368-30 (EudraCT Number); 2024-516158-22-00 (Other Identifier: EU-CTR Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool .

Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.

For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No