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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Squamous Cell Carcinoma of Head and Neck; Colorectal Cancer Metastatic
• Intervention / Treatment: Biological: WU-NK-101 - Dose Escalation; Drug: Cetuximab - Dose Escalation; Biological: WU-NK-101 - Cohort Expansion; Biological: Cetuximab - Cohort Expansion

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WU-NK-101 Monotherapy/Cetuximab combo Run-in; WU-NK-101 is a non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced memory-like anti-tumor NK cell therapy product. Each 8 week cycle in dose escalation is divided into two 28- days segments. Patients will receive WU-NK-101 (Days 1 and 15) in the first segment and a combination of cetuximab (500mg/m2 on Days 29 and 43) plus WU-NK-101 (Days 30 and 44) in the second segment.	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
Experimental: WU-NK-101 /Cetuximab Combo; 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. Depending on response patients may receive up to 6 cycles of treatment.	Biological: WU-NK-101 - Cohort Expansion; WU-NK-101 administered on Days 2 and 16; Biological: Cetuximab - Cohort Expansion; Cetuximab 500mg/m2 administered on Days 1 and 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Maximum Tolerated Dose	Maximum tolerated or administered dose of WU-NK-101 in combination with cetuximab	up to 56 days from first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	Time of response to the time of disease relapse, progression or death due to any cause	24 months
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

Collaborators and Investigators

• Sponsor: Wugen, Inc.
• Investigators: Study Director: Cherry Thomas, MD, Wugen, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2024
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 30, 2022
• First Submitted That Met QC Criteria: December 30, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: cetuximab; NK cells; allogeneic NK cells
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Colonic Diseases; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Colorectal Neoplasms; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Cetuximab
• Other Study ID Numbers: WUN101-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No