Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around
Principal Investigator
by Bridget Keenan, MD
Headshot of Bridget Keenan
Bridget Keenan

Description

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.

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)

Details

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.

Keywords

Colorectal Cancer Metastatic, Squamous Cell Carcinoma of Head and Neck, NK cells, allogeneic NK cells, cetuximab, Carcinoma, Colorectal Neoplasms, Squamous Cell Carcinoma, WU-NK-101 - Dose Escalation, Cetuximab - Dose Escalation, WU-NK-101 - Cohort Expansion, Cetuximab - Cohort Expansion

Eligibility

You can join if…

Open to people ages 18 years and up

  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.

You CAN'T join if...

  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.

Locations

  • UCSF not yet accepting patients
    San Francisco California 94143 United States
  • OU Health Stephenson Cancer Center not yet accepting patients
    Oklahoma City Oklahoma 73117 United States
  • Carolina BioOncology accepting new patients
    Huntersville North Carolina 28078 United States

Lead Scientist at UCSF

  • Bridget Keenan, MD
    I am a physician scientist who works in translational cancer research and medical oncology. My clinical practice is in the Cancer Immunotherapy Clinic, where I work with patients with solid organ cancers who are being treated on early phase immunotherapy trials. I also attend on the Oncology Consult inpatient service.

Details

Status
accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
(estimated)
Sponsor
Wugen, Inc.
ID
NCT05674526
Phase
Phase 1 research study
Study Type
Interventional
Participants
Expecting 30 study participants
Last Updated