Enfortumab Vedotin for Advanced Cancer

Recruiting at 40 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Antimicrobials, Steroids, Immunosuppressants, others

Disqualifiers: CNS metastases, Diabetes, Hepatitis, 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

329 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1. This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab vedotin + pembrolizumab in cohort 9.

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

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not participate in another interventional study while receiving treatment in this trial. It's best to discuss your current medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug Enfortumab Vedotin for advanced cancer?

Enfortumab Vedotin has shown effectiveness in treating advanced urothelial cancer, with a 44% response rate in patients who had previously received other treatments. This means that nearly half of the patients experienced a reduction in cancer size or spread after using this drug. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

Adults with various advanced or metastatic cancers (like breast, lung, gastric, and head & neck cancer) who have measurable disease and are in good physical condition (ECOG 0-1). They must have normal organ function tests, no recent second malignancies or severe neuropathy, not be on active infection treatment, and without HIV or hepatitis B/C. Prior treatments should be completed at least 2 weeks before the trial.

Inclusion Criteria

I am legally an adult and can sign the consent form.

I am fully active or can carry out light work.

You have a medical condition that can be measured using the RECIST Version 1.1 criteria.

Exclusion Criteria

I have active hepatitis B or C.

My diabetes has been under control for the last 3 months.

I haven't had cancer treatments like chemotherapy or immunotherapy in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive enfortumab vedotin on days 1, 8, and 15 every 28-day cycle for cohorts 1 to 8, and enfortumab vedotin on days 1, 8, and pembrolizumab on day 1 every 21-day cycle for cohort 9

Up to 3 years

3 visits per cycle (in-person) for cohorts 1-8, 2 visits per cycle (in-person) for cohort 9

Follow-up

Participants are monitored for safety and effectiveness after treatment with imaging scans every 8 weeks for cohorts 1-8 and every 6 weeks for cohort 9 until disease progression or other criteria are met

Up to 18 months

Regular imaging and assessments

Long-term Follow-up

Participants are contacted every 12 weeks for survival status after disease progression or initiation of new therapy

Until study closure or participant withdrawal

Treatment Details

Interventions

• Enfortumab Vedotin

Trial Overview The study is testing enfortumab vedotin's effectiveness against tumors by looking at response rates and overall survival. For one group (cohort 9), they're also adding pembrolizumab to see if it improves outcomes. Participants will be monitored for how well their tumors respond to these drugs as well as for safety and tolerability.

Participant Groups

Group I: Cohort 9: Head and neck squamous cell carcinoma (HNSCC) Experimental Treatment 2 Interventions

Participants will receive enfortumab vedotin as an IV infusion on days 1 and 8 of each 21-day cycle. Pembrolizumab will be administered as an IV infusion on day 1 of each 21-day cycle.

Group II: Cohort 8: Esophageal squamous cell carcinoma (ESCC) Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group III: Cohort 7: Gastric and esophageal adenocarcinoma (EAC) including GEJ adenocarcinoma Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group IV: Cohort 6: Gastric or GEJ or esophageal cancer Experimental Treatment 1 Intervention

Participants enrolled into Cohort 6 will be reallocated based on disease type and histology into Cohorts 7 or 8. GEJ= gastroesophageal junction

Group V: Cohort 5: Head and neck cancer Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group VI: Cohort 4: Non-squamous non-small cell lung cancer Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group VII: Cohort 3: Squamous non-small cell lung cancer Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group VIII: Cohort 2: Triple negative breast cancer (TNBC) Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Group IX: Cohort 1: HR+/HER2- breast cancer Experimental Treatment 1 Intervention

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. HR+/HER2- = Hormone receptor-positive/ human epidermal growth factor receptor 2-negative

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?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

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 (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 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-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, 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]

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

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

3. 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]

4. 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]

5. Australia pubmed.ncbi.nlm.nih.gov

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