Enfortumab Vedotin for Colorectal and Liver Cancers

Overseen By Cheyenne Schneider

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Steroids, Antimicrobials

Disqualifiers: CNS metastases, Active infection, Cardiac events, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 3 years

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a multi-indication, open-label, single-treatment arm, parallel-cohort phase II study of enfortumab vedotin in adult participants with advanced or metastatic colorectal cancer (CRC) or hepatocellular carcinoma (HCC) who have been previously treated with one or more lines of systemic therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study treatment.

What data supports the effectiveness of the drug Enfortumab Vedotin for treating cancers?

Enfortumab Vedotin has been shown to be effective in treating advanced urothelial cancer, with a 44% response rate in patients who had previously received other treatments. This suggests it might also be effective for other types of cancer, like colorectal and liver cancers, although more research is needed to confirm this. ^{1 2 3 4 5}

What safety information is available for Enfortumab Vedotin?

Enfortumab Vedotin has been associated with several safety concerns, including high blood sugar, nerve damage, eye problems, skin reactions, and risks to unborn babies. Serious skin reactions occurred in up to 47% of patients, and severe side effects were reported in 73% of patients in clinical trials for urothelial cancer. ^{1 3 4 5 6}

What makes the drug Enfortumab Vedotin unique for treating colorectal and liver cancers?

Enfortumab Vedotin is unique because it is an antibody-drug conjugate that targets a specific protein called Nectin-4, which is different from traditional chemotherapy drugs. It has been primarily used for urothelial carcinoma, and its application to colorectal and liver cancers represents a novel approach, as there are no standard treatments specifically targeting Nectin-4 for these cancers. ^{1 2 3 5 6}

Research Team

Tiago Biachi de Castria, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with advanced or metastatic colorectal cancer (CRC) or hepatocellular carcinoma (HCC) who have already tried at least one systemic therapy. Specific details about inclusion and exclusion criteria are not provided, but typically these would cover health status, prior treatments, and other medical conditions.

Inclusion Criteria

Participants must have an anticipated life expectancy of ≥3 months

Participants must agree to use adequate contraception

My colorectal or liver cancer is spreading and cannot be surgically removed, and it's not responding to standard treatments.

Exclusion Criteria

I am on antibiotics for an infection and about to start enfortumab vedotin.

I had a stroke or similar brain event within the last 6 months.

Pregnant women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive enfortumab vedotin as an IV infusion on Days 1, 8, and 15 of every 28-day cycle

Up to 3 years

3 visits per 28-day cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enfortumab Vedotin

Trial Overview The study is testing Enfortumab Vedotin in patients with CRC or HCC. It's an open-label phase II trial, meaning everyone knows they're getting the drug, and it's given to see how effective it is after initial treatments have been tried.

Participant Groups

Group I: Cohort 2: Hepatocellular Carcinoma Experimental Treatment 1 Intervention

Enfortumab vedotin at a dose of 1.25 mg/kg will be administered as an IV infusion over approximately 30 minutes on Days 1, 8, and 15 of every 28-day cycle.

Group II: Cohort 1: Colorectal Cancer Experimental Treatment 1 Intervention

Enfortumab vedotin at a dose of 1.25 mg/kg will be administered as an IV infusion over approximately 30 minutes on Days 1, 8, and 15 of every 28-day cycle.

Enfortumab Vedotin is already approved in United States, European Union for the following indications:

Approved in United States as Padcev for:

• Locally advanced or metastatic urothelial cancer

Approved in European Union as Padcev for:

• Locally advanced or metastatic urothelial cancer

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Findings from Research

Enfortumab vedotin (PADCEV) received accelerated FDA approval for treating locally advanced or metastatic urothelial cancer in patients who have already undergone specific prior therapies, based on substantial evidence from a study involving 125 patients.

The treatment showed a confirmed objective response rate of 44%, with a median response duration of 7.6 months, although 73% of patients experienced grade 3-4 adverse reactions, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. Chang, E., Weinstock, C., Zhang, L., et al.[2022]

Enfortumab vedotin-ejfv (EV) is an effective treatment option for adults with locally advanced or metastatic urothelial carcinoma who have already received PD-1/PD-L1 inhibitors and platinum-based chemotherapy, as it targets the Nectin-4 protein.

To maximize the benefits of EV therapy, it is crucial to educate patients and caregivers, monitor for adverse events, and intervene promptly to manage any side effects that may arise during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. Pace, A., Brower, B., Conway, D., et al.[2021]

Enfortumab vedotin, a treatment for advanced bladder cancer, can cause severe skin reactions, with a case report highlighting a patient who developed toxic epidermal necrolysis shortly after starting the drug.

The case emphasizes the need for careful monitoring of skin reactions and suggests that if such reactions occur, treatment may need to be reduced or stopped to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. Mimura, Y., Kobayashi, A., Utazu, H., et al.[2023]

Enfortumab vedotin (Padcev) is the first FDA-approved treatment specifically for adults with locally advanced or metastatic urothelial cancer who have already undergone treatment with PD-1/PD-L1 inhibitors and platinum-based chemotherapy.

This approval marks a significant advancement in cancer therapy, providing a new option for patients who have limited treatment choices after previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. Kahl, KL.[2023]

Enfortumab vedotin-ejfv (EV) is an effective treatment for locally advanced or metastatic urothelial carcinoma (UC), showing a 44% overall response rate and a median overall survival of 11.7 months in heavily pretreated patients.

While EV demonstrates significant antitumor activity, it also presents unique toxicity concerns that require careful monitoring, highlighting the need for further studies to optimize its use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. Halford, Z., Anderson, MK., Clark, MD.[2021]

In a subgroup analysis of 86 Japanese patients with locally advanced or metastatic urothelial carcinoma, enfortumab vedotin (EV) demonstrated a median overall survival of 15.18 months, significantly longer than the 10.55 months observed with standard chemotherapy.

EV also showed a higher confirmed overall response rate (34.4%) compared to standard chemotherapy (21.3%), while having a lower incidence of treatment-related adverse events, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Japanese subgroup analysis of EV-301: An open-label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma. Matsubara, N., Yonese, J., Kojima, T., et al.[2023]

References

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

FDA Approval Summary: Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma. [2022]

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

Enfortumab Vedotin: Nursing Perspectives on the Management of Adverse Events in Patients With Locally Advanced or Metastatic Urothelial Carcinoma. [2021]

3. Australia pubmed.ncbi.nlm.nih.gov

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma. [2023]

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

FDA Approves First Agent to Treat Locally Advanced, Metastatic Urothelial Cancer. [2023]

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

Enfortumab Vedotin-ejfv: A First-in-Class Anti-Nectin-4 Antibody-Drug Conjugate for the Management of Urothelial Carcinoma. [2021]

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

Japanese subgroup analysis of EV-301: An open-label, randomized phase 3 study to evaluate enfortumab vedotin versus chemotherapy in subjects with previously treated locally advanced or metastatic urothelial carcinoma. [2023]