WU-NK-101 + Cetuximab for Colorectal Cancer

Recruiting at 4 trial locations

Overseen By Eileen McNulty

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Wugen, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disorders, CNS metastases, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

30 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

What 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. ^{1 2 3 6 7}

What 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. ^{3 4 5 8 9}

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.

Research Team

Cherry Thomas, MD

Principal Investigator

Wugen, Inc.

Eligibility 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.

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

Treatment Details

Interventions

• Cetuximab
• WU-NK-101

Trial Overview 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.

Participant Groups

Group I: WU-NK-101 Monotherapy/Cetuximab combo Run-in Experimental Treatment 2 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 Combo Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Wugen, Inc.

Lead Sponsor

Trials

8

Recruited

400+

Findings from Research

In a study of 8 patients with recurrent/advanced colorectal cancer, 6 patients showed a positive response to cetuximab, a targeted therapy that binds to epidermal growth factor receptors (EGFR), indicating its efficacy even in later lines of treatment.

Patients receiving cetuximab in combination with CPT-11 had significantly better progression-free survival (7.3 months) and time to treatment failure (9.3 months) compared to those on cetuximab monotherapy (3.0 months and 4.5 months, respectively), highlighting the potential benefits of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. Katsumoto, Y., Aritake, N., Endoh, A.[2018]

Cetuximab is a monoclonal antibody that targets the epidermal growth factor receptor, which plays a crucial role in the growth of various cancers.

It received accelerated approval from the US FDA in February 2004 for treating metastatic colorectal cancer based on positive tumor response rates observed in Phase II clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab. Goldberg, RM.[2020]

In a post-marketing surveillance study involving 2126 patients with metastatic colorectal cancer, cetuximab was found to be well tolerated, with a median treatment duration of 15.3 weeks and a high incidence of adverse reactions at 89.6%.

The most common adverse reactions included skin disorders (83.7%) and infusion reactions (5.7%), primarily occurring during the first administration, indicating that while side effects are common, they align with previous reports and suggest that cetuximab is clinically useful in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

Cetuximab, a monoclonal antibody targeting the EGFR, has been approved for first-line treatment of KRAS mutation-negative metastatic colorectal cancer (mCRC) in combination with FOLFIRI, showing significant improvements in progression-free survival and overall survival.

The combination of cetuximab with FOLFIRI also resulted in higher objective response rates compared to FOLFIRI alone, making it a valuable treatment option for patients with EGFR-expressing, KRAS wild-type mCRC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

The CIFRA study is investigating the effectiveness of cetuximab combined with irinotecan and fluorouracil in patients with metastatic colorectal cancer who have a specific genetic profile (FcγRIIIa V/V), which may enhance the drug's action through a mechanism called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).

This phase II trial aims to determine if patients with the FcγRIIIa V/V genotype have a higher response rate to cetuximab, potentially improving treatment outcomes, while also assessing safety and survival metrics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. Ottaiano, A., Scala, S., Normanno, N., et al.[2020]

In a study involving 65 patients with advanced colorectal cancer who had previously been treated with multiple therapies, the combination of cetuximab and irinotecan showed a response rate of 20% and a median overall survival of 10.4 months, confirming the efficacy of this treatment regimen.

The treatment was associated with low rates of severe toxicity, with only 8% experiencing grade 3 skin toxicity, indicating that cetuximab and irinotecan can be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. Pfeiffer, P., Nielsen, D., Yilmaz, M., et al.[2018]

Cetuximab and panitumumab are effective treatments for colorectal cancer, showing clinical activity as anti-EGFR monoclonal antibodies, and are generally well tolerated by patients.

While these medications have fewer severe adverse events compared to traditional cytotoxic agents, they can still cause issues like infusion reactions, skin toxicity, lung toxicity, and low magnesium levels, which need to be managed promptly to avoid treatment interruptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. Tsuji, Y., Kogawa, T., Abe, M.[2018]

Cetuximab, when combined with irinotecan, can provide patients with metastatic colorectal cancer an additional 1.7 to 2.0 years of life, indicating its efficacy as a treatment option.

However, the cost-effectiveness analysis revealed that the treatment is quite expensive, with costs per life year gained ranging from 205,536 to 323,040 Euros, highlighting the financial considerations of using cetuximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. Norum, J.[2019]

Cetuximab, an EGFR-inhibiting antibody used for treating certain cancers, is generally considered safe and well-tolerated, but this case highlights the potential for severe complications following its use, particularly in complex surgical situations.

The patient experienced a rare and fatal combination of complications after surgery, raising concerns about the safety of cetuximab in the context of surgical procedures, and emphasizing the need for careful monitoring and documentation of adverse effects in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. Knauer, M., Haid, A., Ammann, K., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[The efficacy of cetuximab for metastatic colorectal cancer]. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Cetuximab. [2020]

3. England pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Cetuximab and irinotecan as third line therapy in patients with advanced colorectal cancer after failure of irinotecan, oxaliplatin and 5-fluorouracil. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

[Anti-epidermal growth factor receptor monoclonal antibodies induced adverse events]. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of metastatic colorectal cancer: a model-based cost-effectiveness analysis. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Complications after oesophagectomy with possible contribution of neoadjuvant therapy including an EGFR-antibody to a fatal outcome. [2021]