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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests enfortumab vedotin, a new treatment for individuals with advanced colorectal or liver cancer. The goal is to evaluate its effectiveness for those who have not responded to other treatments. It is open to individuals with these cancers that are inoperable or have metastasized. Participants should have experienced disease progression after certain standard treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that enfortumab vedotin is likely to be safe for humans?

Research has shown that enfortumab vedotin has been studied in various cancers, including bladder cancer, and is generally well-tolerated. Most side effects are manageable, with common ones including tiredness, skin rash, and changes in blood tests.

For colorectal cancer, safety data collected after the drug's market release indicates it is generally safe. Its use in everyday medical settings provides insights into its effects beyond clinical trials.

In liver cancer, enfortumab vedotin has shown promising results when combined with another drug, reducing the risk of death compared to standard chemotherapy. However, specific side effects for liver cancer treatment are less detailed.

While enfortumab vedotin is still under investigation for colorectal and liver cancers, its use in other cancers offers some insights into its safety. Being in a phase 2 trial suggests some confidence in its safety, but more information is needed to fully understand its effects for these specific cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for colorectal and liver cancers?

Enfortumab vedotin is unique because it targets cancer cells differently than most existing treatments for colorectal and liver cancers. While standard treatments often involve chemotherapy or targeted therapies that focus on specific genetic mutations, enfortumab vedotin is an antibody-drug conjugate. This means it combines an antibody that specifically seeks out cancer cells with a potent drug that kills them. Researchers are excited about this approach because it has the potential to deliver a powerful punch directly to the cancer cells while sparing more of the healthy cells, potentially leading to fewer side effects and improved outcomes.

What evidence suggests that enfortumab vedotin might be an effective treatment for colorectal and liver cancers?

Research has shown that enfortumab vedotin may help treat certain cancers. In this trial, participants with colorectal cancer will receive enfortumab vedotin. Previous studies indicated that about 44% of patients experienced tumor shrinkage, with the effect lasting around 7.6 months on average. For those in the trial cohort with liver cancer, known as hepatocellular carcinoma, enfortumab vedotin has proven effective in similar cancers, such as bladder cancer, where it significantly reduced the risk of death compared to standard treatments. These findings suggest that enfortumab vedotin could be a helpful option for patients with these types of cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Tiago Biachi de Castria, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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-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]

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]

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]

Citations

1. merck.com merck.com/news/seagen-astellas-and-merck-announce-results-of-clinical-trial-investigating-padcev-enfortumab-vedotin-ejfv-with-keytruda-pembrolizumab-and-padcev-as-monotherapy-in-first-line-advanced/

Seagen, Astellas and Merck Announce Results of Clinical ... Results demonstrated a 64.5% confirmed objective response rate in patients treated with investigational combination of enfortumab vedotin and pembrolizumab.

2. withpower.com withpower.com/trial/phase-2-carcinoma-8-2024-31f2f

Enfortumab Vedotin for Colorectal and Liver Cancers 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 ...

3. padcev.com padcev.com/trial-results

Clinical Study Results | PADCEV® (enfortumab vedotin-ejfv) See clinical study data for PADCEV® in adults with advanced bladder cancer or cancers of the urinary tract. See full PI, including Serious Side Effects.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11555717/

Phase 2 Trial of Enfortumab Vedotin in Patients With ... As of May 13, 2022, the median follow‐up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%–54.2%) by IRC and 42.5% (n/N = 17/ ...

5. onclive.com onclive.com/view/pro-data-add-to-efficacy-and-safety-of-frontline-enfortumab-vedotin-pembrolizumab-in-advanced-urothelial-carcinoma

PRO Data Add to Efficacy and Safety of Frontline ... The combination of enfortumab vedotin-ejfv and pembrolizumab nearly doubled progression-free survival and overall survival compared to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11372787/

Post-marketing drug safety surveillance of enfortumab ... This study presents a comprehensive pharmacovigilance analysis of the post-marketing safety profile of EV in the real-world based on the US Food and Drug ...

7. merck.com merck.com/news/keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-reduced-risk-of-event-free-survival-events-by-60-and-risk-of-death-by-50-for-certain-patients-with-muscle-invasive-bladder-ca/

KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab ... KEYTRUDA® (pembrolizumab) Plus Padcev® (enfortumab vedotin-ejfv) Reduced Risk of Event-Free Survival Events by 60% and Risk of Death by 50% for Certain ...

8. onclive.com onclive.com/view/perioperative-enfortumab-vedotin-plus-pembrolizumab-may-represent-new-soc-in-cisplatin-ineligible-mibc

Perioperative Enfortumab Vedotin Plus Pembrolizumab ... Perioperative enfortumab vedotin plus pembrolizumab plus RC + PLND significantly improved EFS (HR, 0.40), OS (HR, 0.50), and pCR (57.1% vs 8.6%) ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761137s018.pdf

Padcev - accessdata.fda.gov Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by ...