Evorpacept + Enfortumab Vedotin for Bladder Cancer

No longer recruiting at 9 trial locations

Overseen By Haiying (Harry) Liu, MD, MPH, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: ALX Oncology Inc.

Must not be taking: MMAE-based ADCs, Anti-CD47

Disqualifiers: CNS metastases, Diabetes, Neuropathy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with advanced bladder cancer that has spread or cannot be surgically removed. It combines two drugs, Evorpacept (an experimental treatment) and Enfortumab Vedotin, to assess their safety and effectiveness together. The trial seeks participants who have previously undergone immune therapies and platinum-based chemotherapy but still experience bladder cancer growth or recurrence. This may suit those who have completed these treatments and meet specific health criteria. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of evorpacept and enfortumab vedotin has promising early safety results, suggesting the treatment is generally well-tolerated. In a study, this combination demonstrated positive effects in patients with advanced bladder cancer, indicating potential safety and effectiveness.

Although this is a Phase 1 trial, which primarily focuses on safety, these initial results are encouraging. Enfortumab vedotin is already known to be effective for bladder cancer, with a good response rate, providing some reassurance about its safety. As new treatments, both drugs undergo close monitoring for side effects, and so far, no major concerns have emerged. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for bladder cancer, which often involve chemotherapy or immunotherapy, Evorpacept combined with Enfortumab Vedotin offers a novel approach by targeting cancer cells more precisely. Enfortumab Vedotin is an antibody-drug conjugate that specifically delivers chemotherapy to cancer cells, reducing harm to healthy cells. Evorpacept, on the other hand, is designed to enhance the immune system's ability to recognize and attack these cancer cells. Researchers are excited about this combination because it could potentially improve the effectiveness of treatment while minimizing side effects, offering new hope for patients with bladder cancer.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that enfortumab vedotin is effective for patients with advanced bladder cancer, achieving a 44% response rate in a study of 125 patients. Nearly half of these patients experienced a reduction or disappearance of their cancer. In this trial, participants will receive a combination of enfortumab vedotin and evorpacept. Early findings suggest that evorpacept may enhance the effectiveness of enfortumab vedotin. This combination could be a strong option for treating urothelial carcinoma, a type of bladder cancer, highlighting its potential to help those with this condition. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with advanced bladder cancer that can't be removed by surgery or has spread, and who have already tried chemotherapy and immune checkpoint inhibitors. They should not have severe nerve damage, active brain metastases, previous treatment with certain drugs like enfortumab vedotin or anti-CD47/SIRPα agents, uncontrolled eye conditions, or diabetes.

Inclusion Criteria

My kidney function is normal.

My bone marrow is working well.

I have been treated with a drug that boosts my immune system.

Exclusion Criteria

I have moderate to severe nerve damage.

I have brain metastases that are causing symptoms or are not under control.

I have been treated with enfortumab vedotin or similar drugs before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Evorpacept (ALX148) infusions every two weeks and Enfortumab Vedotin on Days 1, 8, and 15 of each 28-day cycle

28-day cycles

3 visits per 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
• Evorpacept

Trial Overview The study tests Evorpacept (ALX148) in combination with Enfortumab Vedotin to see how safe they are together and how the body responds. It's an early-phase trial where all participants receive both medications to assess their combined effects on bladder cancer.

How Is the Trial Designed?

Group I: Evorpacept (ALX148) + Enfortumab Vedotin Experimental Treatment 2 Interventions

Phase 1a Dose Escalation: Evorpacept (ALX148) infusions will be administered every two weeks. Enfortumab vedotin will be administered at 1.25 mg/kg IV on Days 1, 8, and 15 of each 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?

ALX Oncology Inc.

Lead Sponsor

Trials

9

Recruited

1,200+

Published Research Related to This Trial

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]

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 showed a 44% overall response rate in a phase II trial involving 125 patients with locally advanced or metastatic urothelial carcinoma who had previously undergone platinum-based chemotherapy and PD-1 or PD-L1 checkpoint inhibitor treatment.

While nearly all patients experienced treatment-related adverse events, most of these side effects were mild to moderate, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enfortumab Vedotin Checks Urothelial Cancer. [2020]

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]

In a study of 29 patients with advanced urothelial carcinoma treated with enfortumab vedotin, the overall response rate was 41%, with median progression-free survival (PFS) of 5.1 months and overall survival (OS) of 10.2 months, indicating the treatment's efficacy in this difficult-to-treat population.

Patients with specific genetic alterations, particularly in TP53 and MDM2, showed improved response rates and survival outcomes, suggesting these alterations could serve as important biomarkers for predicting treatment efficacy with enfortumab vedotin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer. Jindal, T., Zhu, X., Bose, R., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05524545

A Study of Evorpacept (ALX148) With Enfortumab Vedotin ... AT148007 is a Phase 1, open-label, multicenter, safety, pharmacokinetic, pharmacodynamic study of ALX148 in combination with enfortumab vedotin and/or other ...

2. ir.alxoncology.com ir.alxoncology.com/news-releases/news-release-details/alx-oncology-presents-first-evorpacept-combination-data-antibody

Release Details Evorpacept in combination with PADCEV®, an approved antibody-drug conjugate (“ADC”), demonstrated promising activity and was generally well ...

3. bcan.org bcan.org/clinicaltrials/evorpacept-alx148-with-enfortumab-vedotin-for-subjects-with-urothelial-carcinoma-aspen-07/

Evorpacept (ALX148) With Enfortumab Vedotin for ... AT148007 is a Phase 1, open-label, multicenter, safety, pharmacokinetic, pharmacodynamic study of ALX148 in combination with enfortumab vedotin and/or other ...

4. alxoncology.com alxoncology.com/wp-content/uploads/2024/05/Evorpacept-plus-Enfortumab-Vedotin-in-Patients-with-Locally-Advanced-or-Metastatic-Urothelial-Carcinoma-Phase-1a-Dose-Escalation-Results-May24a.pdf

A Phase 1a Study of Evorpacept plus Enfortumab Vedotin ... Here, we present results from the Phase 1a part of the ASPEN-07 study evaluating the safety, tolerability and initial activity of EVO + EV in patients with ...

5. withpower.com withpower.com/trial/phase-1-bladder-cancer-cancer-9-2022-f9327

Evorpacept + Enfortumab Vedotin for Bladder Cancer Enfortumab Vedotin has been shown to be effective for patients with advanced bladder cancer, with a 44% response rate in a study of 125 patients who had ...