The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of HER3-DXd in Subjects With Locally Advanced or Metastatic Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06172478
Recruitment Status : Recruiting
First Posted : December 15, 2023
Last Update Posted : May 17, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Daiichi Sankyo

Brief Summary:
This is a proof-of-concept study designed to investigate HER3-DXd monotherapy in locally advanced or metastatic solid tumors. The study is enrolling cohorts of participants with melanoma [cutaneous/acral], squamous cell carcinomas of the head and neck (SCCHN), and HER2-negative gastric cancer, ovarian carcinoma, cervical cancer, endometrial cancer, bladder cancer, esophageal carcinoma, pancreatic carcinoma, and prostate cancer.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Melanoma Head and Neck Cancer Gastric Cancer Ovarian Carcinoma Cervical Cancer Endometrial Cancer Bladder Cancer Esophageal Cancer Pancreatic Carcinoma Prostate Cancer Drug: HER3-DXd Phase 2

Detailed Description:

This study is designed to assess the safety and efficacy of HER3-DXd monotherapy in subjects with refractory locally advanced or metastatic solid tumors who have been previously treated with ≥1 prior line of systemic anticancer therapy.

The primary objective of the study is to assess the efficacy of HER3-DXd monotherapy for each type of indicated locally advanced or metastatic tumor. Secondary objectives include the assessment of safety and tolerability, efficacy, and pharmacokinetics of HER3-DXd monotherapy for each type of indicated locally advanced or metastatic tumor. HER3 protein expression in tumor tissue and its relationship with HER3-DXd efficacy will also be evaluated.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 26, 2024
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : April 30, 2026


Arm Intervention/treatment
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).
Drug: HER3-DXd
Intravenous infusion 5.6 mg/kg administered Q3W on Day 1 of each 21-day cycle
Other Names:
  • Patritumab Deruxtecan
  • U3-1402




Primary Outcome Measures :
  1. Number of Participants With Objective Response Rate Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months ]
    Confirmed objective response rate (ORR) is defined as the sum of the complete response (CR) rate and partial response (PR) rate based on investigator by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.

  2. Proportion of Participants Achieving a ≥50% Decrease in PSA (Prostate Cancer Cohort Only) [ Time Frame: Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months ]

Secondary Outcome Measures :
  1. Overall Number of Participants With Treatment-emergent Adverse Events Following HER3-DXd Monotherapy (All Cohorts) [ Time Frame: Baseline up to 27 months ]
    Adverse events (AEs) will be coded using MedDRA and AEs and will be graded by using NCI-CTCAE v5.0.

  2. Duration of Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: 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 ]
    Duration of response (DoR) is defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first documentation of progressive disease (PD) or death. The DoR will be calculated for responding participants (PR or CR) only.

  3. Clinical Benefit Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months ]
    Clinical benefit rate (CBR) is the proportion of participants with a best overall response of confirmed CR, confirmed PR, or SD lasting ≥183 days.

  4. Disease Control Rate As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 27 months ]
    Disease control rate is defined as the proportion of participants who have achieved a best overall response of confirmed CR, confirmed PR, or SD (or non-CR/non-PD) by investigator assessment per RECIST v1.1.

  5. Time to Response As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: 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 ]
    Time to response (TTR) will be calculated for confirmed responders only.

  6. Progression-free Survival As Assessed by Investigator Following HER3-DXd Monotherapy (All Cohorts Except Prostate Cancer Cohort) [ Time Frame: 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 ]
  7. Overall Survival Following HER3-DXd Monotherapy (All Cohorts) [ Time Frame: From the start date of study drug to the date of death due to any cause, whichever occurs first, up to approximately 27 months ]
  8. Pharmacokinetic Parameter Maximum Serum Concentration for HER3-DXd (All Cohorts) [ Time Frame: 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) ]
    Maximum serum concentration (Cmax) will be assessed using non-compartmental methods.

  9. Pharmacokinetic Parameter Time to Maximum Serum Concentration for HER3-DXd (All Cohorts) [ Time Frame: 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) ]
    Time to maximum serum concentration (Tmax) will be assessed using non-compartmental methods.

  10. Pharmacokinetic Parameter Trough Serum Concentration (Ctrough) for HER3-DXd (All Cohorts) [ Time Frame: 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) ]
    Trough serum concentration (Ctrough) will be assessed using non-compartmental methods.

  11. Pharmacokinetic Parameter Area Under the Concentration Curve for HER3-DXd (All Cohorts) [ Time Frame: 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) ]
    Area under the concentration-time curve up to the last quantifiable time (AUClast) and Area under the concentration-time curve during dosing interval (AUCtau) will be assessed using non-compartmental methods.

  12. 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) [ Time Frame: 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 ]
  13. Proportion of Participants Achieving a ≥30% Decrease in PSA (Prostate Cancer Cohort Only) [ Time Frame: Baseline, each cycle before infusion (each cycle is 21 days), and end of treatment, up to approximately 27 months ]
  14. Time to First Subsequent Anticancer Therapy (TFST) (Prostate Cancer Cohort Only) [ Time Frame: 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 ]
  15. Time to First Symptomatic Skeletal-Related Event (SSRE) (Prostate Cancer Cohort Only) [ Time Frame: 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 primary 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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06172478


Contacts
Layout table for location contacts
Contact: Daiichi Sankyo Contact for Clinical Trial Information 9089926400 CTRinfo@dsi.com

Locations
Layout table for location information
United States, Missouri
Washington University, School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
United States, Tennessee
SCRI Oncology Partners Recruiting
Nashville, Tennessee, United States, 37203
Japan
Cancer Institute Hospital of JFCR Recruiting
Tokyo, Japan, 135-0550
Sponsors and Collaborators
Daiichi Sankyo
Merck Sharp & Dohme LLC
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo
Layout table for additonal information
Responsible Party: Daiichi Sankyo
ClinicalTrials.gov Identifier: NCT06172478    
Other Study ID Numbers: U31402-277
2023-507641-29-00 ( Other Identifier: EU CTIS )
jRCT2031230575 ( Other Identifier: jRCT )
First Posted: December 15, 2023    Key Record Dates
Last Update Posted: May 17, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: 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.
Access Criteria: 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.
URL: https://vivli.org/ourmember/daiichi-sankyo/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo:
Advanced Solid Tumor
Melanoma
Head and Neck Cancer
Gastric Cancer
Ovarian carcinoma
Cervical cancer
Endometrial cancer
Bladder cancer
Esophageal carcinoma
Pancreatic carcinoma
Prostate cancer
Patritumab Deruxtecan
HER3-DXd
U3-1402
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Prostatic Neoplasms
Melanoma
Stomach Neoplasms
Head and Neck Neoplasms
Uterine Cervical Neoplasms
Urinary Bladder Neoplasms
Endometrial Neoplasms
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Pancreatic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Skin Neoplasms
Skin Diseases
Gastrointestinal Neoplasms