WU-NK-101 + Cetuximab for Colorectal Cancer
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Wugen, Inc.
Must not be taking: Immunosuppressants, Corticosteroids
Disqualifiers: Autoimmune disorders, CNS metastases, Infections, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial.
What data supports the effectiveness of the drug WU-NK-101 + Cetuximab for colorectal cancer?
Cetuximab, a part of the treatment, has shown effectiveness in treating metastatic colorectal cancer by improving progression-free survival and overall survival when combined with other therapies. It works by targeting specific receptors on cancer cells, helping to slow their growth.
12345What safety information is available for the treatment WU-NK-101 + Cetuximab for colorectal cancer?
Cetuximab, used in treating colorectal cancer, is generally well tolerated but can cause side effects like skin reactions, infusion reactions (allergic reactions during drug administration), lung issues, and low magnesium levels. These side effects are manageable, allowing most patients to continue treatment.
12367What makes the drug WU-NK-101 + Cetuximab unique for colorectal cancer treatment?
The drug WU-NK-101 + Cetuximab is unique because it combines a monoclonal antibody that targets the epidermal growth factor receptor (EGFR) with another component, potentially enhancing the immune system's ability to attack cancer cells through a process called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). This approach may offer a novel mechanism compared to standard chemotherapy options.
34589Eligibility Criteria
This trial is for adults with advanced colorectal cancer (CRC) or squamous cell carcinoma of the head and neck (SCCHN) that has worsened despite standard treatments. Participants must have tried all appropriate targeted therapies, have a life expectancy over 12 weeks, measurable disease per RECIST 1.1 criteria, be physically capable of daily activity with limited assistance (ECOG ≤2), and have good heart function.Inclusion Criteria
My advanced colorectal cancer has not improved with standard treatments.
Life expectancy >12 weeks.
My organs are working well.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation Phase
Patients are treated with WU-NK-101, alone and in combination with cetuximab, in successive cohorts using a standard 3 + 3 design. Each 8-week cycle is divided into two 28-day segments.
8 weeks
4 visits (in-person)
Cohort Expansion Phase
Up to 9 additional patients are enrolled in disease-specific expansion cohorts to further characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 cells in combination with cetuximab.
4-24 weeks
2 visits per 4-week cycle (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Participant Groups
The study tests WU-NK-101 in combination with cetuximab to evaluate safety and early anti-tumor effects in two groups: one with CRC and another with SCCHN. It includes a Dose Escalation Phase to find the safe dosage level followed by a Cohort Expansion Phase to further assess its effectiveness.
2Treatment groups
Experimental Treatment
Group I: WU-NK-101 Monotherapy/Cetuximab combo Run-inExperimental Treatment2 Interventions
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.
Group II: WU-NK-101 /Cetuximab ComboExperimental Treatment2 Interventions
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.
Cetuximab is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Erbitux for:
- Locally or regionally advanced squamous cell carcinoma of the head and neck
- Recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
- BRAF V600E mutation-positive metastatic colorectal cancer
🇪🇺 Approved in European Union as Erbitux for:
- Squamous cell carcinoma of the head and neck
- K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Carolina BioOncologyHuntersville, NC
Washington UniversitySaint Louis, MO
University of MinnesotaMinneapolis, MN
UCSFSan Francisco, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Wugen, Inc.Lead Sponsor
References
[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]Cetuximab (Erbitux) is a targeted therapy that used to treat metastatic colorectal cancer. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). We report 6 patients who responded well to cetuximab out of 8 patients with recurrent/advanced colorectal cancer who have received the drug at our hospital since November 2008. Four patients were men and 2 were women, with their ages ranging from 48 to 77 years. The primary cancers were located in the rectum (n=1), sigmoid colon (n=4), and ascending colon (n=1). Performance status (PS) was 0-1. These patients were treated with cetuximab as second-line (n=1), third-line (n=3), fifth-line (n=1), or seventh-line (n=1) therapy. Three patients received cetuximab monotherapy, while the other 3 were given CPT-11 (150 mg/m2, every 2 weeks) as concomitant therapy. Among the 3 patients receiving combination therapy, 2 patients had already received treatment with FOLFIRI. Even in the cetuximab monotherapy group, a partial response (PR) was observed in 2 patients, demonstrating a strong cytoreductive effect. Tumor markers also showed large decreases, with the percent decrease at 1 month being 31.7% and 60.8% in the monotherapy and combination therapy groups, respectively, while it was respectively 14.1% and 29.5% at 2 months. The mean progression-free survival (PFS) time and the time to treatment failure (TTF) were respectively 3.0 months and 4.5 months in the monotherapy group versus 7.3 months and 9.3 months in the combination therapy group. Acneiform rash and paronychia occurred in all 6 patients.
Cetuximab. [2020]Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb) is a monoclonal antibody that binds to the epidermal growth factor receptor, which is important in the growth of many cancers. In February 2004, it was granted accelerated approval by the US FDA for the treatment of metastatic colorectal cancer on the basis of tumour response rates in Phase II trials.
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]Cetuximab (Erbitux(®)) was approved for the treatment of metastatic colorectal cancer in Japan in 2008. To verify information on the safety in practical use of cetuximab, we conducted post-marketing surveillance in accordance with the conditions for approval.
Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]Cetuximab (Erbitux(®)) is a monoclonal antibody that targets the epidermal growth factor receptor (EGFR). In the USA, the approval of cetuximab has been recently expanded to include the first-line treatment of patients with KRAS mutation-negative (wild-type), EGFR-expressing, metastatic colorectal cancer (mCRC) when used in combination with FOLFIRI (irinotecan, fluorouracil, leucovorin [folinic acid]). The addition of cetuximab to first-line treatment with FOLFIRI improved progression-free survival, overall survival, and objective response rates relative to treatment with FOLFIRI alone in patients with EGFR-expressing mCRC with KRAS wild-type tumors. Therefore, cetuximab plus FOLFIRI is a useful biomarker-directed option in the first-line treatment of this patient population.
Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients' selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity.
Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. [2018]Cetuximab (Erbitux) in combination with irinotecan is the most promising combination in heavily pretreated patients with advanced colorectal cancer. Efficacy of this combination was confirmed in the pivotal BOND I study. The aim of the present study was to evaluate efficacy and toxicity of a combination regimen of cetuximab and irinotecan but in contrast to the BOND I study all patients had previously received 5-FU, oxaliplatin and irinotecan and all had progressed during or shortly after completion of treatment. Before January 2005 salvage therapy with cetuximab and irinotecan was not used in Denmark. The Danish government had initiated a national programme for patients with advanced cancer and according to this programme the National Board of Health may approve and finance experimental treatment. From January 2005 to September 2005, 65 consecutive patients were treated with cetuximab (weekly) and irinotecan (each 2 or 3 weeks) at three university hospitals. Median age was 57 years (23-78), and median performance status was 1 (0-3). Response rate was 20%, median TTP was 5.5 months and median OS was 10.4 months. Response and survival was significantly correlated with severity of skin toxicity. Toxicity grade 3 was rare (skin toxicity 8%, diarrhoea 10%, nausea 3%, vomiting 3%, fatigue 8%). Salvage therapy with cetuximab and irinotecan is effective in patients pretreated with irinotecan, and oxaliplatin and in a general population the results from the BOND I study was confirmed.
[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. [2018]Cetuximab and panitumumab, both anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAb), have demonstrated clinical activity in patients with colorectal cancer. They are well tolerated, but they involve various adverse events that are rare among cytotoxic agents. Typical adverse events associated with anti-EGFR MAbs include infusion reaction, skin toxicity, lung toxicity, and hypomagnesemia. It is necessary to recognize and manage adverse events promptly to continue treatments without drug discontinuation. This report details the adverse events and their management with anti-EGFR MAbs use.
Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. [2019]Cetuximab (Erbitux) has shown activity in patients with metastatic colorectal cancer (mCRC). To evaluate the cost-effectiveness of this drug combined with irinotecan in mCRC, a model-based cost-effectiveness analysis (CEA) was performed. Data on cetuximab obtained from Medline in December 2004 and from the 2004 ASCO-meeting were analyzed for life years gained (LYG) with regard to the use of this monoclonal antibody (MAb). Norwegian prices as of January 2005 were employed. The LYG ranged between 1.7 and 2.0 years. The median cost per patient treated was calculated to 34,256 Euro to 45,764 Euro yielding a cost per LYG in the range between 205,536 Euro and 323,040 Euro. Sensitivity analysis documented price of cetuximab and survival gain to be the major factors influencing the cost-effectiveness ratio. In conclusion, the analysis indicates cetuximab to be a promising, but very expensive antibody.
Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. [2021]Different molecular therapies like the EGFR-inhibiting antibody cetuximab have come into clinical practice. Cetuximab is EMEA-approved for metastatic colorectal cancer and advanced squamous-cell head and neck cancer. Administration is said to be safe and well tolerated with common, usually mild dermatologic side effects.