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)

Cancer Categories

Breast,Gastrointestinal (GI),Gynecologic,Lung

Karmanos Trial ID

2024-099

NCT ID

NCT06695845

Age Group

Adult

Scope

National

Phase

Phase II

Principal Investigator

Ira
Winer, M.D., Ph.D., FACOG
Oncology - Gynecologic, Oncology - Surgical View Profile

Objective:

Primary Objectives:

To evaluate the antitumor activity of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors

Secondary Objectives:

To assess other antitumor efficacy parameters of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors
To evaluate the safety and tolerability of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors
To evaluate the PK of zanidatamab
To evaluate the immunogenicity of zanidatamab
To evaluate participant-reported tolerability of zanidatamab monotherapy in participants with locally advanced, unresectable, or metastatic HER2-overexpressing (IHC 3+) solid tumors

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Eligibility

Inclusion Criteria:

Is at least 18 years of age inclusive at the time of signing the informed consent
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.
HER2 overexpression (IHC 3+) must be determined by a sponsor designated central laboratory.
All participants must have adequate tumor sample for submission to allow central HER2 testing.
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)
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Has a life expectancy of at least 3 months, in the opinion of the investigator.
Participants with history of treated and stable CNS metastases are eligible, provided the following criteria are met:

Participants also have measurable metastatic disease with HER2 overexpression (IHC 3+) outside the CNS.
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.
Prior stereotactic radiosurgery or stereotactic radiotherapy should be completed at least 7 days (≥ 7 days) before the first dose of study intervention.

Adequate organ functions.
Females of childbearing potential must have a negative pregnancy test result.
Females of childbearing potential and males with a partner of childbearing potential must be willing to use 2 methods of birth control.

Exclusion Criteria:

Has known or suspected leptomeningeal disease and/or untreated brain metastasis.
Has uncontrolled or significant cardiovascular disease
Has ongoing toxicity related to prior cancer therapy
Has uncontrolled infection or requiring IV antibiotics, antivirals, or antifungals.
Has known Human Immunodeficiency Virus (HIV) infection.
Has active hepatitis B or C infection.
Has an active SARS-CoV-2 infection.
Has a history of life-threatening hypersensitivity to monoclonal antibody (mAbs) or to recombinant proteins or excipients in the drug formulation of zanidatamab.
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.
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.
Prior treatment with HER2-targeted therapy (Cohort 1 only).
Has a history of trauma or major surgery
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.
Received zanidatamab at any time prior to the current study.
Colorectal Cancer (CRC) participants with known KRAS/NRAS and BRAF mutations.
Non-Small Cell Lung Cancer (NSCLC) participants with known ALK, EGFR mutations and ROS1 fusion.
Female participants who are breastfeeding or pregnant, and female and male participants planning a pregnancy.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices