Daratumumab for Bladder and Kidney Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Tyrosine kinase inhibitors, PD-1/PD-L1 inhibitors

Must not be taking: Corticosteroids, Antivirals

Disqualifiers: Active infection, Cardiovascular disease, Brain metastases, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 20

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of daratumumab in treating metastatic renal cell carcinoma (a type of kidney cancer) and muscle invasive bladder cancer. Researchers seek to determine how effectively the treatment stops cancer progression and achieves specific responses, such as reducing tumor size or achieving cancer-free tissue in bladder cancer. Ideal participants have documented cases of these cancers, have experienced failed previous treatments, and show no evidence of active infections or significant heart issues. As an Early Phase 1 trial, this study focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently enrolled in another interventional study or have received another investigational agent within 28 days, you may not be eligible. It's best to discuss your specific medications with the trial team.

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

Research has shown that daratumumab, also known as DARZALEX, has been tested in many patients. Studies involving over 2,400 people with multiple myeloma (a type of blood cancer) have found that the treatment is generally well-tolerated. However, serious side effects, such as allergic reactions and severe reactions at the injection site, can occur. These factors are important to consider when deciding to join a trial.

Regarding safety, the FDA has already approved daratumumab for treating multiple myeloma. This approval indicates a known safety profile, although risks might vary depending on the condition being treated.

Currently, early trials are testing daratumumab for bladder and kidney cancer. At this stage, researchers are focusing on its safety and tolerability for patients with these types of cancer. This means much remains to be learned about its safety in this new context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike traditional treatments for bladder and kidney cancer that primarily rely on chemotherapy and surgical intervention, daratumumab offers a novel approach by harnessing the power of the immune system. Daratumumab is a monoclonal antibody that specifically targets CD38, a protein expressed on cancer cells, marking them for destruction by the immune system. Researchers are excited about daratumumab because it provides a targeted therapy option that could potentially lead to fewer side effects compared to conventional chemotherapy. Additionally, the unique mechanism of action may offer benefits in managing cancer that is resistant to standard treatments.

What evidence suggests that daratumumab might be an effective treatment for bladder and kidney cancer?

Research has shown that daratumumab, a type of targeted therapy, yields promising results in treating various cancers. In this trial, participants with bladder cancer will receive daratumumab. Studies indicate that daratumumab can help patients live longer without disease progression, suggesting its potential effectiveness for muscle invasive bladder cancer as well.

For participants with kidney cancer, daratumumab has improved patient response to treatment and extended the time without disease worsening. Although direct data for kidney cancer is limited, these results in similar conditions suggest it could help manage advanced kidney cancer. The treatment targets a specific protein on cancer cells, potentially stopping their growth. ^{6 7 8 9 10}

Who Is on the Research Team?

Matthew Campbell, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with muscle invasive bladder cancer or metastatic kidney cancer who are not pregnant, have an ECOG performance status of <=2, and meet specific health criteria like blood counts and organ function. They must not be on other trials, have certain infections (like HIV), or untreated brain metastases. Participants should agree to use contraception during the study.

Inclusion Criteria

Your hemoglobin level needs to be at least 9 g/dL within 4 days before starting the daratumumab treatment.

Your blood albumin level is at least 2.8 g/dl within 4 days before taking the first dose of daratumumab.

My white blood cell count is healthy without needing medication.

Exclusion Criteria

I am not participating in another drug study.

I have been tested for hepatitis B and C, and understand my infection status.

RENAL COHORT: The subject has received any other type of investigational agent within 28 days before the first dose of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment (Bladder Cancer Cohort)

Participants receive daratumumab by vein 1 time each week for 4 weeks before cystectomy

4 weeks

4 visits (in-person)

Surgery (Bladder Cancer Cohort)

Participants undergo cystectomy during weeks 6-8

2 weeks

1 visit (in-person)

Follow-up (Bladder Cancer Cohort)

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment (Renal Cancer Cohort)

Participants receive daratumumab by vein 1 time each week for 8 weeks before nephrectomy, metastasectomy, or biopsy

8 weeks

8 visits (in-person)

Surgery/Biopsy (Renal Cancer Cohort)

Participants undergo nephrectomy, metastasectomy, or biopsy during weeks 10-12

2 weeks

1 visit (in-person)

Extended Treatment (Renal Cancer Cohort)

Participants may receive additional doses of daratumumab every 2 weeks for 4 months and then monthly for 1 year

12 months

Bi-weekly visits for 4 months, then monthly visits

Follow-up (Renal Cancer Cohort)

Participants are monitored for safety and effectiveness after treatment

13 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The trial tests daratumumab's safety and effectiveness in treating these cancers. It includes a nephrectomy (kidney removal) for kidney cancer patients, biopsies to examine tissue samples, laboratory biomarker analysis to monitor responses, and possibly a metastasectomy if there are isolated areas of spread that can be surgically removed.

How Is the Trial Designed?

Group I: Cohort 2 Bladder (daratumumab) Experimental Treatment 2 Interventions

Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter beginning at week 1. Cycles repeat every week for up to 4 weeks in the absence of disease progression or unacceptable toxicity.

Group II: Cohort 1 Renal (daratumumab, biopsy, surgery) Experimental Treatment 5 Interventions

Patients receive daratumumab IV over 8 hours for the first dose and then over 4 hours for all doses thereafter during weeks 1-8. Treatment repeats every week for up to 8 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo biopsy, nephrectomy, or metastasectomy during weeks 10-12. Patients may then restart treatment with daratumumab beginning 2 weeks after biopsy or 4-6 weeks after nephrectomy or metastasectomy. Cycles repeat every 2 weeks for 4 months and then monthly for 1 year in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Citations

1. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/darzalex-faspro-daratumumab-and-hyaluronidase

DARZALEX FASPRO® (daratumumab and hyaluronidase) The median overall survival (OS) was not reached in the D-Rd arm and was 65.5 months in the Rd arm (HR, 0.66; 95% CI, 0.53-0.83; P=0.0003).

2. cancerletter.com cancerletter.com/clinical-roundup/20251024_8j/

Tecvayli + Darzalex Faspro improve PFS and OS vs. ... Trodelvy reduces risk of disease progression or death by 38% vs. chemo as first-line therapy in metastatic TNBC. Data from the phase III ASCENT- ...

3. cancernetwork.com cancernetwork.com/view/subcutaneous-daratumumab-improves-pfs-in-smoldering-multiple-myeloma

Subcutaneous Daratumumab Improves PFS in Smoldering ... The 60-month OS rates were 93.0% and 86.9%, respectively; data showed a strong positive trend toward longer OS with daratumumab (HR, 0.52; 95% ...

4. jnj.com jnj.com/media-center/press-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care

TECVAYLI® plus DARZALEX FASPRO® combination ... At almost three years follow-up, the combination of TECVAYLI and DARZALEX FASPRO met the primary endpoint of progression-free survival (PFS) ( ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.gov Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO [see. Adverse Reactions (6.3)]. Systemic Reactions. In a ...

7. darzalex.com darzalex.com/isi/

Important Safety Information for DARZALEX® FASPRO Find important safety information for DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). See Full Prescribing and Safety Information.

8. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/170456-316022/daratumumab-intravenous

Daratumumab: uses, dosing, warnings, adverse events, ... The median overall survival was 28.2 months for subcutaneous daratumumab/hyaluronidase-fihj versus 25.6 months for IV daratumumab. Combination Therapy with ...

9. darzalexhcp.com darzalexhcp.com/

DARZALEX® (daratumumab) & DARZALEX FASPRO ... In addition to the safety data presented in the study, here is some other safety information to consider in older patients across the DARZALEX® clinical trials.

10. darzalex.com darzalex.com/about-darzalex-and-darzalex-faspro/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... It is not known if DARZALEX FASPRO® is safe and effective in children. Important Safety Information. IMPORTANT SAFETY INFORMATION. Do not receive DARZALEX ...