EU101 for Solid Cancers

Recruiting at 5 trial locations

Overseen By Seoyoun Kim, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eutilex

Must not be taking: Anti-CD137, Corticosteroids

Disqualifiers: CNS tumor, Active infection, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

110 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1 (Dose Escalation) of this study will assess the safety, tolerability, dose-limiting toxicity (DLT), and will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of EU101 in participants with advanced solid tumors. Phase 2 (Dose Expansion) of the study will assess the antitumor effect of EU101 in two indications including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on systemic corticosteroids or other immunosuppressive medications one week before starting the trial.

What data supports the effectiveness of the drug EU101 for solid cancers?

The research shows that drugs targeting the epidermal growth factor receptor (EGFR), like necitumumab, have improved survival in lung cancer patients when combined with other treatments. This suggests that targeting EGFR, which may be a component of EU101, could be effective in treating solid cancers. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with advanced solid tumors, including colorectal and non-small cell lung cancer, where standard treatments have failed or aren't suitable. Participants must be in relatively stable health with a life expectancy of at least 12 weeks and have adequate organ function. Women who can bear children and sexually active men must use effective contraception.

Inclusion Criteria

Voluntarily provided a written consent to participate in the study

My blood tests show normal organ function and I don't have anemia or infections.

I agree to use two effective birth control methods during and for 12 weeks after the study.

Exclusion Criteria

I have previously been treated with an anti-CD137 agent.

My doctor thinks I shouldn't join the study.

I have had noninfectious hepatitis in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Participants receive EU101 intravenously once every 3 weeks with escalating doses to determine the maximum tolerated dose and recommended Phase 2 dose

Approximately 24 months

Every 3 weeks (in-person)

Phase 2: Dose Expansion

Participants with CRC and NSCLC receive EU101 intravenously once every 3 weeks at the recommended Phase 2 dose to assess antitumor effect

Approximately 24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• EU101

Trial Overview The study is testing EU101's safety and dosage limits in Phase 1, then its effectiveness against specific cancers in Phase 2. It involves gradually increasing doses to find the highest dose that doesn't cause unacceptable side effects (MTD) and deciding on the best dose for further studies (RP2D).

Participant Groups

Group I: EU101: Dose Expansion Cohort 2 Experimental Treatment 1 Intervention

Participants with NSCLC will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with a determined recommended phase 2 dose until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.

Group II: EU101: Dose Expansion Cohort 1 Experimental Treatment 1 Intervention

Participants with CRC will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with a determined recommended phase 2 dose until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.

Group III: EU101: Dose Escalation Cohort Experimental Treatment 1 Intervention

Participants with advanced solid tumors will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with escalating doses starting from 0.05 milligrams per kilogram (mg/kg) to 10 mg/kg until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.

EU101 is already approved in United States, China for the following indications:

Approved in United States as EU101 for:

• Advanced solid tumors
• Colorectal cancer (CRC)
• Non-small cell lung cancer (NSCLC)

Approved in China as Eutilex for:

• Advanced solid tumors

Who Is Running the Clinical Trial?

Eutilex

Lead Sponsor

Trials

4

Recruited

210+

Findings from Research

In a study of 96 German patients with advanced squamous non-small-cell lung cancer, adding the anti-EGFR antibody necitumumab to standard treatment (gemcitabine and cisplatin) significantly reduced the risk of death by 41% and the risk of disease progression by 44%.

The safety profile of necitumumab was manageable, with common side effects like rash and hypomagnesemia, and it showed a delay in appetite loss compared to standard treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE). Reck, M., Thomas, M., Kropf-Sanchen, C., et al.[2022]

In a randomized phase II trial involving 106 patients with advanced pancreatic cancer, the combination of gemcitabine and S-1 significantly improved progression-free survival (PFS) to 5.4 months compared to 3.6 months with gemcitabine alone.

The combination therapy also showed a longer overall survival (OS) of 13.5 months versus 8.8 months for gemcitabine alone, although this difference was not statistically significant, indicating potential benefits without increased severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Nakai, Y., Isayama, H., Sasaki, T., et al.[2022]

The combination of anti-EGFR antibody Erbitux (cetuximab) and anti-VEGFR2 antibody DC101 demonstrated significant antitumor synergy in preclinical models of pancreatic and colon cancer, with a combination index indicating strong interaction (CI = 0.1, P < 0.01).

This synergistic effect is likely due to overlapping impacts on tumor cell proliferation and vascularization, with VEGF production and hypoxia-inducible factor 1alpha serving as potential molecular links between the two pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Tonra, JR., Deevi, DS., Corcoran, E., et al.[2018]

Matuzumab, a fully humanized monoclonal antibody targeting the ErbB-1 receptor, significantly reduced tumor growth and metastasis in pancreatic cancer models, demonstrating strong antiproliferative and proapoptotic effects.

When combined with gemcitabine, matuzumab enhanced its therapeutic efficacy, showing prolonged antitumor activity even with short-term treatment, indicating a promising strategy for pancreatic cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matuzumab short-term therapy in experimental pancreatic cancer: prolonged antitumor activity in combination with gemcitabine. Kleespies, A., Ischenko, I., Eichhorn, ME., et al.[2022]

In a study of 982 patients with stage IV squamous non-small cell lung cancer (sq-NSCLC), the addition of necitumumab to standard chemotherapy (gemcitabine and cisplatin) significantly improved overall survival for patients with tumors expressing EGFR protein, with a median survival of 11.7 months compared to 10.0 months for those receiving chemotherapy alone.

The treatment was generally well tolerated, although patients receiving necitumumab experienced higher rates of certain adverse events, such as hypomagnesemia and skin rash, particularly in those with EGFR-expressing tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer. Paz-Ares, L., Socinski, MA., Shahidi, J., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Necitumumab plus Gemcitabine and Cisplatin as First-Line Therapy in Patients with Stage IV EGFR- Expressing Squamous Non-Small-Cell Lung Cancer: German Subgroup Data from an Open-Label, Randomized Controlled Phase 3 Study (SQUIRE). [2022]

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

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Matuzumab short-term therapy in experimental pancreatic cancer: prolonged antitumor activity in combination with gemcitabine. [2022]

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

Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer. [2022]