Clinical trial NCT05674526: A Phase 1b Study of WU-NK-101 in Combination With Cetuximab
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer Metastatic
Squamous Cell Carcinoma of Head and Neck
Keywords: NK cells
allogeneic NK cells
cetuximab
Lead sponsor: Wugen, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Adverse Events of WU-NK-101 in combination with cetuximab as assessed by by CTCAE v5
timeFrame: 24 months
measure: Maximum Tolerated Dose
timeFrame: up to 56 days from first dose
Secondary outcomes:
measure: Duration of Response
timeFrame: 24 months
measure: Overall Response Rate
timeFrame: 24 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF
state: California
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
Study officials:
affiliation: Wugen, Inc.
name: Cherry Thomas, MD
role: STUDY_DIRECTOR
References: