A Phase 1b Study of WU-NK-101 in Combination With Cetuximab

Colorectal Cancer Metastatic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05674526
• Other study ID #: WUN101-02
• Status: Recruiting
• Phase: Phase 1
• Start date: May 21, 2024
• Est. completion date: June 1, 2026

Study information

• Verified date: June 2024
• Source: Wugen, Inc.
• Contact: Eileen McNulty
• Phone: 314-501-1968
• Email: emcnulty[@]wugen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

In the Dose Escalation Phase, up to 12 patients with either advanced and/or metastatic CRC or advanced and/or metastatic SCCHN will be treated with WU-NK-101, alone and in combination with cetuximab, in successive cohorts of 3 to 6 patients using a standard 3 + 3 design. Intra-patient dose escalation is not permitted. Patients may receive up to one 8-week cycle of treatment. Each 8-week cycle is divided into two 28-day segments, (Segments A and B).

During Segment A, only WU-NK-101 (monotherapy) will be administered. Segment A will consist of two doses of WU-NK-101 infused on Day 1 and Day 15. Patients that do not experience a dose limiting toxicity (DLT) will proceed to Segment B.

During Segment B, WU-NK-101 will be administered in combination with cetuximab (combination therapy). WU-NK-101 cells will be administered on Days 30 and 44. Cetuximab will be administered on Days 29 and 43 at 500 mg/m2 (FDA-approved dose).

Once the MTD/MAD is defined in the Dose Escalation Phase, up to 9 additional patients will be enrolled in 2 parallel, disease specific, expansion cohorts (Cohort 1 [patients with CRC] and Cohort 2 [patients with SCCHN]) to further characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 cells in combination with cetuximab. Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle.

At the end of Cycle 2, patients who achieve a partial response (PR) or stable disease (SD) may receive up to 4 additional cycles of treatment of WU-NK-101 cells in combination with cetuximab with disease assessments on Day 28 (+/- 3 days) of each even numbered cycle, for a maximum of 6 cycles.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 1, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Colorectal Cancer Metastatic
• Colorectal Neoplasms
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• WU-NK-101 - Dose Escalation
WU-NK-101 administered on Days 1, 15, 30 and 44

Drug:
• Cetuximab - Dose Escalation
Cetuximab 500mg/m2 administered on Days 29 and 43

Biological:
• WU-NK-101 - Cohort Expansion
WU-NK-101 administered on Days 2 and 16
• Cetuximab - Cohort Expansion
Cetuximab 500mg/m2 administered on Days 1 and 15

Locations

Country	Name	City	State
United States	Carolina BioOncology	Huntersville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wugen, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events of WU-NK-101 in combination with cetuximab as assessed by by CTCAE v5	Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until the end of the study visit or at the end of treatment visit.	24 months
Primary	Maximum Tolerated Dose	Maximum tolerated or administered dose of WU-NK-101 in combination with cetuximab	up to 56 days from first dose
Secondary	Duration of Response	Time of response to the time of disease relapse, progression or death due to any cause	24 months
Secondary	Overall Response Rate	ORR is defined as the proportion of patients that achieve complete remission (CR) + partial response (PR) using modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	24 months