Colorectal Cancer Metastatic, Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
NK cells, allogeneic NK cells, cetuximab
Brief 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.
Interventions
BIOLOGICALWU-NK-101 - Dose Escalation
WU-NK-101 administered on Days 1, 15, 30 and 44
DRUGCetuximab - Dose Escalation
Cetuximab 500mg/m2 administered on Days 29 and 43
BIOLOGICALWU-NK-101 - Cohort Expansion
WU-NK-101 administered on Days 2 and 16
BIOLOGICALCetuximab - Cohort Expansion
Cetuximab 500mg/m2 administered on Days 1 and 15
Sponsors
Wugen, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Exclusion criteria
Experienced toxicities related to prior cetuximab treatment which required permanent discontinuation of cetuximab per the current label.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events of WU-NK-101 in combination with cetuximab as assessed by by CTCAE v5 | 24 months | 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. |
| Maximum Tolerated Dose | up to 56 days from first dose | Maximum tolerated or administered dose of WU-NK-101 in combination with cetuximab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 24 months | Time of response to the time of disease relapse, progression or death due to any cause |
| Overall Response Rate | 24 months | 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) |
Countries
United States
Outcome results
None listed