Evorpacept + Enfortumab Vedotin for Bladder Cancer

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

36 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug 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 previously received other treatments. This drug was approved by the FDA based on this evidence, although further trials are needed to confirm its benefits. ^{1 2 3 4 5}

What makes the drug Evorpacept + Enfortumab Vedotin unique for bladder cancer?

This drug combination is unique because Enfortumab Vedotin is an antibody-drug conjugate that targets Nectin-4, a protein found on cancer cells, and has shown effectiveness in patients who have already tried other treatments like PD-1/PD-L1 inhibitors and platinum-based chemotherapy. Evorpacept, which blocks the CD47/SIRPa pathway, may enhance the immune system's ability to attack cancer cells, potentially improving outcomes. ^{2 3 4 5 6}

What is the purpose of this trial?

This trial is testing a new treatment (ALX148) combined with another cancer drug (enfortumab vedotin) and possibly other treatments. It targets patients with urothelial carcinoma, a type of bladder cancer. ALX148 helps the immune system fight cancer, while enfortumab vedotin directly attacks the cancer cells.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 (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 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]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Somatic alterations of TP53 and MDM2 associated with response to enfortumab vedotin in patients with advanced urothelial cancer. [2023]

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

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

4. 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]

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

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

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

Enfortumab Vedotin Checks Urothelial Cancer. [2020]