A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors

A Phase 2, Open-label, Multicenter Study to Evaluate Efficacy and Safety of Zanidatamab for the Treatment of Participants With Previously Treated HER2-expressing Solid Tumors (DiscovHER PAN-206)

The purpose of this study is to evaluate the efficacy and safety of zanidatamab for the treatment of participants with previously treated solid tumors that have Human Epidermal Growth Factor Receptor 2 (HER2) Immunohistochemistry (IHC) 3+ overexpression.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Ovarian Cancer; Endometrial Cancer; Non-small Cell Lung Cancer; Urothelial Carcinoma; Salivary Gland Cancer; Gastroesophageal Cancer; HER-2 Protein Overexpression
• Intervention / Treatment: Drug: Zanidatamab

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Study Locations

• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 13620
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul
    • Gangnam-gu, Seoul, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
    • Jongno-gu, Seoul, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
    • Seodaemun-gu, Seoul, South Korea, 03722
      • Recruiting
      • Severance Hospital
• United States
  • Arizona
    • Prescott, Arizona, United States, 86301
      • Recruiting
      • Arizona Oncology Associates, PC - NAHOA
  • Colorado
    • Littleton, Colorado, United States, 80120
      • Recruiting
      • Rocky Mountain Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Recruiting
      • Florida Cancer Specialists - South
    • Orlando, Florida, United States, 32827
      • Recruiting
      • Florida Cancer Specialists - Lake Nona
    • St. Petersburg, Florida, United States, 33705
      • Recruiting
      • Florida Cancer Specialists - North
    • West Palm Beach, Florida, United States, 33401
      • Recruiting
      • Florida Cancer Specialists - East
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Recruiting
      • Affiliated Oncologists
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Barbara Ann Karmanos Cancer Institute
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • Recruiting
      • Alliance Cancer Specialists
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Recruiting
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Amarillo, Texas, United States, 79124
      • Recruiting
      • Texas Oncology - West Texas
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology - DFW
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78217
      • Recruiting
      • Texas Oncology - San Antonio
  • Virginia
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Blue Ridge Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is at least 18 years of age inclusive at the time of signing the informed consent
2. Participants with locally advanced, unresectable, or metastatic solid tumors (except Biliary Tract Cancer (BTC), defined as gallbladder cancer or cholangiocarcinoma) who have progressed following at least 1 prior systemic treatment for metastatic or advanced disease and have no available treatment options that have confirmed benefit. Prior treatment with HER2-targeted therapy is not permitted (Cohort 1 only). For participants with breast cancer (Cohort 2) or GEA (Cohort 3), prior HER2-targeted therapy is permitted and prior therapy with trastuzumab deruxtecan (T-DXd) is required.
3. HER2 overexpression (IHC 3+) must be determined by a sponsor designated central laboratory.
4. All participants must have adequate tumor sample for submission to allow central HER2 testing.
5. Presence of at least 1 measurable lesion as assessed by Independent Central Review (ICR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Has a life expectancy of at least 3 months, in the opinion of the investigator.

8. Participants with history of treated and stable CNS metastases are eligible, provided the following criteria are met:

   1. Participants also have measurable metastatic disease with HER2 overexpression (IHC 3+) outside the CNS.
   2. Participants with treated CNS metastases that are no longer symptomatic may be included in the study if they recovered to < Grade 1 (CTCAE Version 5.0 or higher) or baseline from the acute toxic effect associated with the treatment > 7 days prior to Cycle 1 Day 1.
   3. Prior stereotactic radiosurgery or stereotactic radiotherapy should be completed at least 7 days (≥ 7 days) before the first dose of study intervention.
9. Adequate organ functions.
10. Females of childbearing potential must have a negative pregnancy test result.
11. Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion Criteria:

1. Has known or suspected leptomeningeal disease and/or untreated brain metastasis.
2. Has uncontrolled or significant cardiovascular disease
3. Has ongoing toxicity related to prior cancer therapy
4. Has uncontrolled infection or requiring IV antibiotics, antivirals, or antifungals.
5. Has known Human Immunodeficiency Virus (HIV) infection.
6. Has active hepatitis B or C infection.
7. Has an active SARS-CoV-2 infection.
8. Has a history of life-threatening hypersensitivity to monoclonal antibody (mAbs) or to recombinant proteins or excipients in the drug formulation of zanidatamab.
9. Has any serious underlying medical or psychiatric condition that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site.
10. Has any issue or condition that, in the opinion of the investigator, would contraindicate the participant's participation in the study or confound the results of the study.
11. Prior treatment with HER2-targeted therapy (Cohort 1 only).
12. Has a history of trauma or major surgery
13. Was treated with systemic antineoplastic therapy, including hormonal therapies for breast cancer, or any investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to Cycle 1 Day 1.
14. Received zanidatamab at any time prior to the current study.
15. Colorectal Cancer (CRC) participants with known KRAS/NRAS and BRAF mutations.
16. Non-Small Cell Lung Cancer (NSCLC) participants with known ALK, EGFR mutations and ROS1 fusion.
17. Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.
18. Prior or concurrent invasive malignancy other than the disease under study, whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanidatamab treatment arm; Eligible participants receiving zanidatamab treatment	Drug: Zanidatamab; Administered by intravenous (IV) infusion; Other Names: ZW25; JZP598; ZIIHERA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Objective Response Rate (cORR) per RECIST Version 1.1, as assessed by ICR	The Independent Central Review (ICR) assessed cORR is defined as the proportion of participants who had a best overall response of Complete Response (CR), or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	Up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) Per RECIST Version 1.1, as assessed by ICR	ICR assessed DOR is defined as the time in months from the first objective response (CR or PR) that is subsequently confirmed to documented progressive disease (PD) per RECIST v1.1 or death from any cause.	Up to 2.5 years
cORR by RECIST Version 1.1, as assessed by Investigator	Investigator assessed cORR is defined as the proportion of participants who had a best overall response of Complete Response (CR), or Partial Response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	Up to 2.5 years
Duration of Response (DOR) Per RECIST Version 1.1, as assessed by Investigator	Investigator assessed DOR is defined as the time in months from the first objective response (CR or PR) that is subsequently confirmed to documented progressive disease (PD) per RECIST v1.1 or death from any cause.	Up to 2.5 years
Time to Response (TTR), as assessed by ICR	ICR assessed TTR is defined as the time from the first dosing date to the first objective response (CR or PR) per RECIST v1.1.	Up to 2.5 years
Time to Response (TTR), as assessed by Investigator	Investigator assessed TTR is defined as the time from the first dosing date to the first objective response (CR or PR) per RECIST v1.1.	Up to 2.5 years
Disease control rate (DCR), as assessed by ICR	ICR assessed DCR is defined as the proportion of participants whose best overall response (BOR) is confirmed CR, or PR, or stable disease using the RECIST version 1.1 criteria	Up to 2.5 years
Disease control rate (DCR), as assessed by Investigator	Investigator assessed DCR is defined as the proportion of participants whose best overall response (BOR) is confirmed CR, or PR, or stable disease using the RECIST version 1.1 criteria	Up to 2.5 years
Progression Free Survival (PFS), as assessed by ICR	PFS is defined as the time in months from the first dosing date to the date of first documented disease progression (as assessed by ICR according to RECIST v1.1) or death from any cause, whichever occurs first.	Up to 2.5 years
Progression Free Survival (PFS), as assessed by Investigator	PFS is defined as the time in months from the first dosing date to the date of first documented disease progression (as assessed by Investigator according to RECIST v1.1) or death from any cause, whichever occurs first.	Up to 2.5 years
Overall Survival (OS)	OS is defined as the time in months from randomization to the date of death due to any cause.	Up to 3.5 years
Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) As Graded by NCI CTCAE Version 5.0		Up to 2.5 years
Number of Participants With Dose Reductions		Up to 2.5 years
Number of Participants Discontinuing Study Treatment Due to TEAEs		Up to 2.5 years
Serum Concentrations of Zanidatamab		Up to 2.5 years
Number of Participants Positive for Anti-drug Antibodies to Zanidatamab		Up to 2.5 years
Number of participants reporting Symptomatic Adverse Events based on Patient-reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAE)		Up to 2.5 years
Number of participants reporting Symptomatic Adverse Events based on European Organisation for Research and Treatment of Cancer (EORTC) Item Library		Up to 2.5 years
Percentage of all treated participants reporting overall side-effect bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5)		Up to 2.5 years
Percentage of time when participants on treatment reported a high side-effect bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5)		Up to 2.5 years

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals
• Collaborators: Jazz Pharmaceuticals Ireland Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 16, 2024
• First Submitted That Met QC Criteria: November 16, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: ZW25; JZP598; HER2 IHC 3+ Overexpression Solid Tumors
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Mouth Diseases; Stomatognathic Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Esophageal Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Salivary Gland Diseases; Mouth Neoplasms; Skin and Connective Tissue Diseases; Stomach Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Endometrial Neoplasms; Carcinoma, Transitional Cell; Salivary Gland Neoplasms; zanidatamab
• Other Study ID Numbers: JZP598-206; 2024-516551-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy contact clinicaldatasharing@jazzpharma.com.

Drug and device information, study documents

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