A Phase 1b Study of WU-NK-101 in Combination With Cetuximab for Advanced and/or Metastatic Colorectal Cancer (CRC) and Advanced and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

WUN101-02

This study is a Phase 1b open-label study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 in combination with cetuximab in patients with advanced and/or metastatic CRC (Cohort 1), and in patients with advanced and/or metastatic SCCHN (Cohort 2). The overall study will be comprised of two phases, a Dose Escalation Phase, and a Cohort Expansion Phase.

2024-06-01

2025-02-28

2026-06-01

Not yet recruiting

Early phase I

30

Inclusion Criteria: 1. Patients must have a histologically confirmed diagnosis of advanced and/or metastatic CRC that has failed or progressed beyond first line or higher line standard of care therapy including bevacizumab combination, cetuximab combination, 5-FU based regimens, or checkpoint inhibitors alone or in combination. Patients must have received all targeted therapies for which they are eligible. Patients may be included in this study regardless of mutation status (e.g., RAS-mutant, wild-type, or unknown status, BRAF V600E, etc.) and EGFR expression. Or, Patients must have a histologically confirmed diagnosis of SCCHN that has failed or progressed beyond first or higher line standard of care therapy including cetuximab alone or in combination, checkpoint inhibitors alone and in combination, or regimens containing radiotherapy. Patients may be included in this study regardless of EGFR expression. 2. Measurable disease, in accordance with RECIST 1.1. 3. Eastern Cooperative Oncology Group Performance (ECOG) Status ≤ 2 at screening. 4. Adequate organ function as defined in the protocol. 5. Ejection fraction ≥ 45%. 6. Life expectancy \>12 weeks. Exclusion Criteria: 1. Experienced toxicities related to prior cetuximab treatment which required permanent discontinuation of cetuximab per the current label. 2. Active autoimmune disorder requiring immunosuppression (physiologic steroids defined as ≤ 15 mg prednisone or equivalent are acceptable). 3. Symptomatic central nervous system (CNS) metastases. Patients with a history of CNS metastasis must have been treated, must be asymptomatic, and must not have any of the following at the time of enrollment: No concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids \> 10 mg prednisone/day or equivalent). No progression of CNS metastases on magnetic resonance imaging (MRI) or computed tomography (CT) for at least 14 days after last day of prior therapy for the CNS metastases, no concurrent leptomeningeal disease or cord compression. 4. Known hypersensitivity to one or more of the study agents. 5. Known hypersensitivity to IL-2 or any component of IL-2 formulation. 6. Patients with organ allografts. 7. Uncontrolled or untreated bacterial, fungal, or viral infections, including but not limited to human immunodeficiency virus, hepatitis B or C infection, or uncontrolled infection of any etiology. 8. Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (ECG) suggestive of acute ischemia, active conduction system abnormalities, or abnormal cardiac stress test. 9. New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections). 10. Received any investigational drugs within the 14 days or 5 half- lives (whichever is longer) prior to the first dose of fludarabine. 11. Radiotherapy or chemotherapy within 2 weeks prior to the first dose of fludarabine. 12. Severe renal impairment, defined as creatinine clearance \<40 mL/min. 13. Pregnant and/or breastfeeding women. 14. Any condition that, in the opinion of the investigator, would prevent the participant from consenting to or participating in the study.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'In dose expansion patients will be enrolled in 2 parallel, disease specific cohorts to further characterize the safety, tolerability and preliminary anti- tumor activity of WU-NK-101 in combination with cetuximab', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 30, 'type': 'ESTIMATED'}}

2023-12-05