Trial Title:
A Phase 1b Study of WU-NK-101 in Combination With Cetuximab
NCT ID:
NCT05674526
Condition:
Colorectal Cancer Metastatic
Squamous Cell Carcinoma of Head and Neck
Conditions: Official terms:
Carcinoma
Colorectal Neoplasms
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Cetuximab
Conditions: Keywords:
NK cells
allogeneic NK cells
cetuximab
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Intervention model description:
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
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
WU-NK-101 - Dose Escalation
Description:
WU-NK-101 administered on Days 1, 15, 30 and 44
Arm group label:
WU-NK-101 Monotherapy/Cetuximab combo Run-in
Intervention type:
Drug
Intervention name:
Cetuximab - Dose Escalation
Description:
Cetuximab 500mg/m2 administered on Days 29 and 43
Arm group label:
WU-NK-101 Monotherapy/Cetuximab combo Run-in
Intervention type:
Biological
Intervention name:
WU-NK-101 - Cohort Expansion
Description:
WU-NK-101 administered on Days 2 and 16
Arm group label:
WU-NK-101 /Cetuximab Combo
Intervention type:
Biological
Intervention name:
Cetuximab - Cohort Expansion
Description:
Cetuximab 500mg/m2 administered on Days 1 and 15
Arm group label:
WU-NK-101 /Cetuximab Combo
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.
Detailed 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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCSF
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bridget Keenan, MD
Email:
hdfccc.cip@ucsf.edu
Investigator:
Last name:
Bridget Keenan, MD
Email:
Principal Investigator
Facility:
Name:
University of Minnesota
Address:
City:
Minneapolis
Zip:
55455
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Naomi Fujioka, MD
Investigator:
Last name:
Naomi Fujioka, MD
Email:
Principal Investigator
Facility:
Name:
Washington University
Address:
City:
Saint Louis
Zip:
63108
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Katie Stricker
Investigator:
Last name:
Patrick Grierson, MD
Email:
Principal Investigator
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
David Levitz, MD
Investigator:
Last name:
David Levitz, MD
Email:
Principal Investigator
Facility:
Name:
Carolina BioOncology
Address:
City:
Huntersville
Zip:
28078
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ashley Wallace
Email:
awallace@carolinabiooncology.org
Investigator:
Last name:
John Powderly, MD
Email:
Principal Investigator
Facility:
Name:
OU Health Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73117
Country:
United States
Status:
Recruiting
Contact:
Last name:
Manu Pandey, MD
Investigator:
Last name:
Manu Pandey, MD
Email:
Principal Investigator
Start date:
May 21, 2024
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Wugen, Inc.
Agency class:
Industry
Source:
Wugen, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05674526
