Clinical trial NCT06695845: A Phase 2 Study of Zanidatamab in Patients With HER2-expressing Tumors
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Cancer
Gastric Cancer
Esophageal Cancer
Gastroesophageal Cancer
Colorectal Cancer
Endometrial Cancer
Non-small Cell Lung Cancer
Ovarian Cancer
Urothelial Carcinoma
Salivary Gland Cancer
Pancreatic Cancer
HER-2 Protein Overexpression
Keywords: JZP598
ZW25
HER2 IHC 3+ Overexpression Solid Tumors
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Jazz Pharmaceuticals Ireland Limited
First posted: 2024-11-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Confirmed Objective Response Rate (cORR) per RECIST Version 1.1, as assessed by ICR
timeFrame: Up to 2.5 years
Secondary outcomes:
measure: Duration of Response (DOR) Per RECIST Version 1.1, as assessed by ICR
timeFrame: Up to 2.5 years
measure: cORR by RECIST Version 1.1, as assessed by Investigator
timeFrame: Up to 2.5 years
measure: Duration of Response (DOR) Per RECIST Version 1.1, as assessed by Investigator
timeFrame: Up to 2.5 years
measure: Time to Response (TTR), as assessed by ICR
timeFrame: Up to 2.5 years
measure: Time to Response (TTR), as assessed by Investigator
timeFrame: Up to 2.5 years
measure: Disease control rate (DCR), as assessed by ICR
timeFrame: Up to 2.5 years
measure: Disease control rate (DCR), as assessed by Investigator
timeFrame: Up to 2.5 years
measure: Progression Free Survival (PFS), as assessed by ICR
timeFrame: Up to 2.5 years
measure: Progression Free Survival (PFS), as assessed by Investigator
timeFrame: Up to 2.5 years
measure: Overall Survival (OS)
timeFrame: Up to 3.5 years
measure: Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) As Graded by NCI CTCAE Version 5.0
timeFrame: Up to 2.5 years
measure: Number of Participants With Dose Reductions
timeFrame: Up to 2.5 years
measure: Number of Participants Discontinuing Study Treatment Due to TEAEs
timeFrame: Up to 2.5 years
measure: Serum Concentrations of Zanidatamab
timeFrame: Up to 2.5 years
measure: Number of Participants Positive for Anti-drug Antibodies to Zanidatamab
timeFrame: Up to 2.5 years
measure: Number of participants reporting Symptomatic Adverse Events based on Patient-reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAE)
timeFrame: Up to 2.5 years
measure: Number of participants reporting Symptomatic Adverse Events based on European Organisation for Research and Treatment of Cancer (EORTC) Item Library
timeFrame: Up to 2.5 years
measure: Percentage of all treated participants reporting overall side-effect bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5)
timeFrame: Up to 2.5 years
measure: 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)
timeFrame: Up to 2.5 years
Other outcomes:
Locations:
city: Prescott
country: United States
facility: Arizona Oncology Associates, PC - NAHOA
state: Arizona
city: Littleton
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South
state: Florida
city: Orlando
country: United States
facility: Florida Cancer Specialists - Lake Nona
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East
state: Florida
city: Chicago Ridge
country: United States
facility: Affiliated Oncologists
state: Illinois
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Horsham
country: United States
facility: Alliance Cancer Specialists
state: Pennsylvania
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists
state: Tennessee
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology - West Texas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio
state: Texas
city: Roanoke
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Gangnam-gu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Seodaemun-gu
country: Korea, Republic of
facility: Severance Hospital
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
Study officials:
References: