Brief Title: Zanidatamab in Patients With HER2-expressing Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Confirmed Objective Response Rate (cORR) per RECIST Version 1.1

Primary Outcome 1 - Timeframe: Up to 2.5 years

Primary Outcome 2 - Measure: as assessed by ICR

Primary Outcome 2 - Timeframe: N/A

CONDITION

• 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

ELIGIBILITY

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+) via Immunohistochemistry (IHC).

- 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. Prior stereotactic radiosurgery or stereotactic radiotherapy should be completed at least 7 days (≥ 7 days) before the first dose of study intervention.

- 3. Recovery to no more than Grade 1 or baseline from any acute toxicity associated with the treatment.

- 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 severe acute respiratory syndrome coronavirus 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 enrollment.

- 14. Was treated in a prior clinical study of zanidatamab or 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: Clinical Trial Disclosure & Transparency

Phone: 215-832-3750

Email: [email protected]

LOCATION