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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06172478




Registration number
NCT06172478
Ethics application status
Date submitted
7/12/2023
Date registered
15/12/2023

Titles & IDs
Public title
A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors
Scientific title
HERTHENA-PanTumor01 (U31402-277): A Phase 2, Multicenter, Multicohort, Open-Label, Proof of Concept Study of Patritumab Deruxtecan (HER3-DXd; U3-1402) in Subjects With Locally Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
2023-507641-29-00
Secondary ID [2] 0 0
U31402-277
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Melanoma 0 0
Head and Neck Cancer 0 0
Gastric Cancer 0 0
Ovarian Carcinoma 0 0
Cervical Cancer 0 0
Endometrial Cancer 0 0
Bladder Cancer 0 0
Esophageal Cancer 0 0
Pancreatic Carcinoma 0 0
Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Stomach
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)
Cancer 0 0 0 0
Bladder - transitional cell cancer
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - HER3-DXd

Experimental: HER3-DXd Monotherapy - Participants with locally advanced or metastatic cancer (melanoma, head and neck, gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer) will receive an intravenous infusion of HER3-DXd monotherapy 5.6 mg/kg every 3 weeks (Q3W).


Treatment: Drugs: HER3-DXd
Intravenous infusion 5.6 mg/kg administered Q3W on Day 1 of each 21-day cycle
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Objective Response Rate Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [1] 0 0
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Primary outcome [2] 0 0
Proportion of Participants Achieving a =50% Decrease in PSA (Prostate Cancer Cohort Only)
Timepoint [2] 0 0
Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months
Secondary outcome [1] 0 0
Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts)
Timepoint [1] 0 0
Baseline up to 27 months
Secondary outcome [2] 0 0
Duration of Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [2] 0 0
From the date of first documentation of confirmed response (CR or PR) to the first documentation of objective progression or to death due to any cause, whichever occurs first, up to approximately 27 months
Secondary outcome [3] 0 0
Clinical Benefit Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [3] 0 0
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Secondary outcome [4] 0 0
Disease Control Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [4] 0 0
Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months
Secondary outcome [5] 0 0
Time to Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [5] 0 0
From the start date of study drug to the date of the first documentation of response (CR or PR) that is subsequently confirmed, up to approximately 27 months
Secondary outcome [6] 0 0
Progression-free Survival As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort)
Timepoint [6] 0 0
From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed by investigator per RECIST v1.1 or death due to any cause, whichever occurs first, up to approximately 27 months
Secondary outcome [7] 0 0
Overall Survival Following HER3-DXd Monotherapy (All Cohorts)
Timepoint [7] 0 0
From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 27 months
Secondary outcome [8] 0 0
Pharmacokinetic Parameter Maximum Serum Concentration for HER3-DXd (All Cohorts)
Timepoint [8] 0 0
Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8; Cycle 1: Day 15 (each cycle is 21 days)
Secondary outcome [9] 0 0
Pharmacokinetic Parameter Time to Maximum Serum Concentration for HER3-DXd (All Cohorts)
Timepoint [9] 0 0
Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8; Cycle 1: Day 15 (each cycle is 21 days)
Secondary outcome [10] 0 0
Pharmacokinetic Parameter Trough Serum Concentration (Ctrough) for HER3-DXd (All Cohorts)
Timepoint [10] 0 0
Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8; Cycle 1: Day 15 (each cycle is 21 days)
Secondary outcome [11] 0 0
Pharmacokinetic Parameter Area Under the Concentration Curve for HER3-DXd (All Cohorts)
Timepoint [11] 0 0
Cycles 1-4, 6, 8: Day 1, predose and postdose; Cycles 1 and 3: Day 1, 2 hours and 4 hours postdose; Cycles 1 and 3: Day 8; Cycle 1: Day 15 (each cycle is 21 days)
Secondary outcome [12] 0 0
Radiographic Progression-free Survival (rPFS) As Assessed by Prostate Cancer Working Group 3 (PCWG3) Criteria by the Investigator or Death Due to Any Cause Following HER3-DXd Monotherapy (Prostate Cancer Cohort Only)
Timepoint [12] 0 0
From the start date of study drug to the earlier date of the first objective documentation of radiographic disease progression as assessed per PCWG3 criteria by investigator or death due to any cause, whichever occurs first, up to approximately 27 months
Secondary outcome [13] 0 0
Proportion of Participants Achieving a =30% Decrease in PSA (Prostate Cancer Cohort Only)
Timepoint [13] 0 0
Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months
Secondary outcome [14] 0 0
Time to First Subsequent Anticancer Therapy (TFST) (Prostate Cancer Cohort Only)
Timepoint [14] 0 0
From the start date of study drug to initiation of the first subsequent anticancer therapy or death, whichever occurs first, up to approximately 27 months
Secondary outcome [15] 0 0
Time to First Symptomatic Skeletal-Related Event (SSRE) (Prostate Cancer Cohort Only)
Timepoint [15] 0 0
From start date of study drug to the first occurrence of any of the following: Use of EBRT, New symptomatic pathologic bone fracture, Spinal cord compression, A tumor-related orthopedic surgical intervention, up to approximately 27 months

Eligibility
Key inclusion criteria
Inclusion Criteria

Participants must meet all of the following criteria to be eligible for enrollment into the study:

1. Sign and date the informed consent form prior to the start of any study-specific qualification procedures. A separate tissue screening consent will be obtained from all subjects to meet the baseline tumor tissue requirement.
2. Participants aged =18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
3. Has locally advanced unresectable or metastatic disease (not curable by surgery or radiation) as follows:

Cutaneous (acral and non-acral) melanoma
1. Histologically or cytologically confirmed cutaneous (acral or non-acral) melanoma
2. Disease progression while on or after having received treatment with =1 prior line of anti-programmed cell death protein (PD-1) or anti-programmed death-ligand 1 (PD-L1) based therapy (previous use of other immune checkpoint inhibitors [ICIs] [ie, anti-CTLA4, anti- LAG-3] is acceptable). Prior anti-PD-(L)1 therapy in the adjuvant setting is allowed if there is recurrence within 12 weeks of the last dose. If the participant had BRAFm melanoma, they must have had disease progression on BRAF/MEK inhibitor therapy as well.

Squamous cell carcinomas of the head and neck
3. Squamous cell carcinoma of the head and neck (with a primary location of oral cavity,oropharynx, larynx, hypopharynx) that is human papillomavirus (HPV) positive or negative (as determined by local standard). Excludes tumor location in the nasopharynx, nasal cavity, paranasal sinuses, and unknown primary locations.
4. Disease progression after having received treatment with =1 and <3 prior lines of systemic therapy in the unresectable recurrent or metastatic setting.

Must have had disease progression on anti-PD-(L)1 (either as monotherapy or in combination with chemotherapy or other therapies). Must also have had disease progression on a platinum-based chemotherapy (PBC) regimen either in the recurrent or metastatic setting or in the locally advanced setting with curative intent.

Gastric or GEJ adenocarcinoma
5. Tumor tissue must be confirmed as negative for HER2 expression (immunohistochemistry [IHC] 0/1+ or IHC 2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
6. Disease progression after having received treatment with =2 prior lines of therapy that include PBC with or without anti-PD-1 therapy.

Ovarian Carcinoma
7. Pathologically documented high-grade serous epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer.
8. Documented disease progression =4 weeks after the last dose of PBC and <6 months of last dose of PBC in the advanced or metastatic setting. Prior use of folate reductase alpha targeting antibody-drug conjugate (ADC) (ie, mirvetuximab soravtansine) is allowed.

Cervical Cancer
9. Pathologically or cytologically documented recurrent or persistent squamous, adenosquamous, or adenocarcinoma of the uterine cervix.
10. Disease progression after having received =1 line of systemic therapy in the recurrent or metastatic setting. This may include prior anti-PD-(L)1 treatment and/or tissue factor directed ADC (tisotumab vedotin [TV]) per regional standard of care.

Endometrial Cancer
11. Pathologically or cytologically documented endometrial cancer (carcinoma of any histological sub-type or endometrial carcinosarcoma), irrespective of microsatellite instability (MSI) or mismatch repair (MMR) status.
12. Documented disease progression after having received =1 prior line of therapy (maximum of 3) PBC containing systemic treatment and an anti-PD(L)-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

Bladder Cancer
13. Pathologically or cytologically documented locally advanced/unresectable or metastatic urothelial carcinoma of the bladder, renal pelvis, ureter, or urethra. Histological variants are allowed if urothelial histology is predominant. Small cell/neuroendocrine tumors are not allowed even if mixed histology.
14. Relapsed or progressed after treatment with =1 prior line of therapy (maximum of 3) that contains anti-PD-(L)1 therapy in the perioperative or metastatic setting. At least 1 line of therapy must also contain one of the following treatment modalities: chemotherapy or enfortumab vedotin. Prior fibroblast growth factor receptor (FGFR)-inhibitor treatment for those who are eligible are allowed.

* Required treatments can be given in combination or sequentially
* Prior cisplatin-based therapy or PD-(L)1 inhibitor therapy given for the treatment of muscle invasive urothelial carcinoma is counted as 1 line of therapy
* The same regimen administered twice in different disease settings will be counted as 1 line of prior therapy
* A minimum of 20 subjects in the second-line setting who have previously received enfortumab vedotin and pembrolizumab in combination will be enrolled.

Esophageal Carcinoma
15. Pathologically or cytologically documented esophageal squamous cell carcinoma.
16. Must have documented disease progression after having received 2 prior lines of therapy including previous PBC with or without an anti-PD-1 therapy-containing regimen (combined or sequential) in the advanced/metastatic setting.

Pancreatic Carcinoma
17. Pathologically or cytologically documented unresectable or metastatic pancreatic adenocarcinoma.
18. Relapsed or disease progression after having received 1 prior line of systemic therapy in the locally advanced/metastatic setting.

Prostate Cancer
19. Pathologically or cytologically documented unresectable locally advanced or metastatic castration-resistant prostate cancer (CRPC).
20. Adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology.
21. Surgically or medically castrated, with testosterone levels of <50 ng/dL.
22. Documented objective progression as determined by radiographic progression for subjects with measurable disease after androgen deprivation.
23. Relapsed or disease progression after having received treatment with =1 of the following novel hormonal agents: abiraterone, enzalutamide, apalutamide, or darolutamide.
24. Relapsed or disease progression after having received =1 cytotoxic chemotherapy regimen that included a taxane.
4. Has =1 measurable lesion on CT or MRI as per RECIST v1.1 by investigator assessment. Prostate cancer participants with bone only disease may be eligible.
5. Provides a pretreatment tumor tissue sample of sufficient quantity, as defined in the Study Laboratory Manual. The following tissue samples can be provided as the pretreatment tumor tissue sample:

1. Tissue collected from a biopsy (from =1 lesion not previously irradiated) performed since progression while on or after treatment with the most recent systemic cancer therapy regimen and prior to signing of the tissue ICF

OR
2. Pretreatment tumor biopsy from =1 lesion not previously irradiated and amenable to sampling after signing of the tissue ICF. The pretreatment tissue requirement may be waived after discussion and agreement with the Sponsor.
6. Has Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Participants who meet any of the following criteria will be disqualified from entering the study:

1. Has HER2-positive gastric cancer as classified by ASCO-CAP guidelines and determined prior to enrollment by assessment in a local laboratory that is Clinical Laboratory Improvement Amendments certified (US sites) or accredited based on specific country regulations.
2. Has nasopharyngeal cancer.
3. Has mucosal or uveal melanoma.
4. Has a history of (non-infectious) interstitial lung disease (ILD), that required corticosteroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
5. Has clinically severe respiratory compromise (based on the investigator's assessment) resulting from intercurrent pulmonary illnesses
6. Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1.

Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
7. Had prior treatment with an anti-HER3 antibody and/or antibody-drug conjugate (ADC) that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan).
8. Has history of other active malignancy within 3 years prior to Cycle 1 Day 1, except the following:

1. Adequately treated nonmelanoma skin cancer
2. Adequately treated intraepithelial carcinoma of the cervix
3. Any other curatively treated in situ disease
9. Has any evidence of severe or uncontrolled diseases (eg, active bleeding diatheses, active serious infection) psychiatric illness/social situations, geographical factors, substance abuse, or other factors that, in the investigator's opinion, make it high risk for the subject to participate in the study or that would jeopardize compliance with the protocol
10. Has previously received irinotecan treatment in the advanced or metastatic disease setting.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Icon Cancer Centre Chermside - Chermside
Recruitment hospital [2] 0 0
Monash Medical Centre Clayton - Clayton
Recruitment hospital [3] 0 0
Icon Cancer Centre Hobart - Hobart
Recruitment hospital [4] 0 0
Icon Cancer Centre Townsville - Hyde Park
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
4812 - Hyde Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Belgium
State/province [7] 0 0
Bruxelles
Country [8] 0 0
Belgium
State/province [8] 0 0
Edegem
Country [9] 0 0
Belgium
State/province [9] 0 0
Jette
Country [10] 0 0
Belgium
State/province [10] 0 0
Leuven
Country [11] 0 0
France
State/province [11] 0 0
Bordeaux
Country [12] 0 0
France
State/province [12] 0 0
Dijon
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Marseille
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Toulouse
Country [18] 0 0
France
State/province [18] 0 0
Villejuif
Country [19] 0 0
Japan
State/province [19] 0 0
Hidaka
Country [20] 0 0
Japan
State/province [20] 0 0
Kashiwa-shi
Country [21] 0 0
Japan
State/province [21] 0 0
Matsuyama-shi
Country [22] 0 0
Japan
State/province [22] 0 0
Nagoya
Country [23] 0 0
Japan
State/province [23] 0 0
Osakasayama-shi
Country [24] 0 0
Japan
State/province [24] 0 0
Sunto-gun
Country [25] 0 0
Japan
State/province [25] 0 0
Tokyo
Country [26] 0 0
Japan
State/province [26] 0 0
Yokohama
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seongnam
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Sevilla
Country [32] 0 0
Spain
State/province [32] 0 0
Valencia
Country [33] 0 0
Taiwan
State/province [33] 0 0
Kaohsiung
Country [34] 0 0
Taiwan
State/province [34] 0 0
Tainan
Country [35] 0 0
Taiwan
State/province [35] 0 0
Taipei
Country [36] 0 0
Taiwan
State/province [36] 0 0
Taoyuan
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Coventry
Country [38] 0 0
United Kingdom
State/province [38] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Global Clinical Leader
Address 0 0
Daiichi Sankyo
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Daiichi Sankyo Contact for Clinical Trial Information
Address 0 0
Country 0 0
Phone 0 0
9089926400
Fax 0 0
Email 0 0
CTRinfo@dsi.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data (IPD) on completed studies and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF)
When will data be available (start and end dates)?
Completed studies that has reached a global end or completion with all data set collected and analyzed, and for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Available to whom?
Formal request from qualified scientific and medical researchers on IPD and clinical study documents on completed clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/ourmember/daiichi-sankyo/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06172478