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

NCT04639219 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: D967MC000012024-516158-22-002020-002368-30
• Study Type: interventional
• Target: 102
• Locations: 9 countries
• Sites: 30

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.

Conditions

Advanced Solid Tumors With HER2 Mutation,eg:Colorectal,Urothelial,Gastric, Hepatobiliary,Endometrial,Melanoma,Ovarian,Cervical,Salivary Gland,Pancreatic,Breast

Keywords

HER2; T-DXd; DS-8201a; Trastuzumab Deruxtecan; Metastatic; Solid Tumors; Histology Agnostic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

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

  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

  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

  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

  At Months 6 and 12

• Confirmed ORR as Per RECIST v1.1 Using Investigator Assessment

  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)

Study Arms (1)

T-DXd

EXPERIMENTAL

T-DXd monotherapy

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

Trastuzumab deruxtecan (T-DXd) by intravenous infusion

Also known as: DS-8201a (T-DXd)

T-DXd

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo Co., Ltd.: collaborator

Study Sites (30)

Research Site

Santa Rosa, California, 95403, United States

Location

Research Site

Muncie, Indiana, 47303, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Middletown, New Jersey, 07748, United States

Location

Research Site

Commack, New York, 11725, United States

Location

Research Site

Harrison, New York, 10604, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Fairfax, Virginia, 22031, United States

Location

Research Site

Anderlecht, 1070, Belgium

Location

Research Site

Toronto, CA, M5G 2M9, Canada

Location

Research Site

Copenhagen, 2100, Denmark

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Bordeaux, 33076, France

Location

Research Site

Lyon, 69008, France

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Research Site

Villejuif, 94805, France

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Milan, 20141, Italy

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Milan, 20162, Italy

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Naples, 80131, Italy

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Research Site

Chūōku, 104-0045, Japan

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Kashiwa, 277-8577, Japan

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Research Site

Suita-shi, 565-0871, Japan

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 06351, South Korea

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Research Site

Barcelona, 08035, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Madrid, 28050, Spain

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Research Site

Pamplona, 31008, Spain

Location

Research Site

Seville, 41013, Spain

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

Related Links

• Redacted CSR synopsis
• Redacted SAP
• Redacted CSP

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: None (open-label)
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 20, 2020
• Study Start: December 30, 2020
• Primary Completion: January 25, 2023
• Study Completion (Estimated): July 14, 2026
• Last Updated: March 23, 2026
• Results First Posted: February 15, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

JP (3); BE (1); FR (3); DK (1); US (10); ES (5); KR (3); CA (1); IT (3)