Darzalex Faspro for Blood Cancers

Overseen By Amanda Stevens, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Anti-CD38 therapies

Disqualifiers: COPD, Asthma, HIV, Hepatitis, 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: 4

Duration: 4 weeks

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to investigate the safety and effectiveness of Darzalex Faspro (daratumumab and hyaluronidase-fihj) (a monoclonal antibody that targets plasma cells that make antibodies) and whether it can lower donor specific antibodies (DSA) levels to low enough levels to permit patients to proceed with allogeneic peripheral blood transplant (alloBMT). Those being asked to participate have high DSA levels that puts those being asked to participate at high risk of rejecting the available donor's blood stem cells and making those being asked to participate ineligible to receive a stem cell transplant.

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. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Darzalex Faspro for blood cancers?

Research shows that Daratumumab, a key component of Darzalex Faspro, is effective in treating multiple myeloma, a type of blood cancer. It works by targeting a protein on cancer cells, leading to their destruction, and has shown promising results both alone and in combination with other treatments. ^{1 2 3 4 5}

What makes Darzalex Faspro unique compared to other blood cancer drugs?

Darzalex Faspro is unique because it combines daratumumab, an antibody that targets cancer cells, with hyaluronidase, which helps the drug be absorbed under the skin, allowing for quicker and more convenient subcutaneous (under the skin) administration compared to traditional intravenous (into the vein) treatments. ^{6 7 8 9 10}

Research Team

Christian Gocke

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults with certain blood cancers or conditions like leukemia, lymphoma, and myelodysplastic syndrome who are at high risk of stem cell transplant rejection due to high donor specific antibodies. They must be over 18, willing to participate in a clinical trial, have adequate organ function for the transplant and no other suitable donors.

Inclusion Criteria

I am 18 years old or older.

All potential Participants must be pre-approved by BMT faculty consensus.

Subjects are eligible if there are high levels of Donor Specific Antibody levels based on protocol specific scoring system regardless of prior attempts at standard desensitization.

Exclusion Criteria

Known hypersensitivity or intolerance to boron or mannitol, sorbitol, corticosteroids, monoclonal antibodies or human proteins, or the excipients.

My lung function is less than half of what is expected for someone my age and size.

I have been treated with Daratumumab or another anti-CD38 therapy before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 weekly doses of Darzalex Faspro followed by standard desensitization regimen and allogeneic stem cell transplant

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of DSA levels and recovery metrics

2 years

Treatment Details

Interventions

• Darzalex Faspro

Trial Overview The study tests Darzalex Faspro's ability to lower donor specific antibody levels enough for patients to undergo an allogeneic peripheral blood stem cell transplant safely. It aims to see if this treatment can prevent the rejection of transplanted cells in those at high risk.

Participant Groups

Group I: Daratumumab-SC followed by standard of care DSA desensitization and alloBMT Experimental Treatment 2 Interventions

Darzalex Faspro (Daratumumab and hyaluronidase-fihj) will be administered subcutaneously (SC) weekly (every 7 day +/- 1 day) for a total of four doses followed by standard desensitization regimen and allogeneic stem cell transplant.

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

Approved in United States as Darzalex Faspro for:

• Newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone
• Relapsed or refractory multiple myeloma in combination with pomalidomide and dexamethasone
• Relapsed or refractory multiple myeloma in combination with carfilzomib and dexamethasone
• Monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent

Approved in European Union as Darzalex for:

• Multiple myeloma in combination with lenalidomide and dexamethasone
• Multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone
• Relapsed or refractory multiple myeloma in combination with pomalidomide and dexamethasone
• Monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

The combination of daratumumab, bortezomib, and dexamethasone (Dvd) significantly enhances the effectiveness of expanded natural killer (NK) cells in targeting multiple myeloma, as shown in a mouse model.

Dvd treatment not only increased the cytotoxicity of NK cells but also improved their persistence and ability to home to tumor sites, leading to reduced tumor burden and prolonged survival in treated mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model. Thangaraj, JL., Ahn, SY., Jung, SH., et al.[2023]

FcRL5 is highly expressed on plasma cells in multiple myeloma, making it a promising target for antibody-drug conjugates (ADCs) that can selectively deliver cytotoxic drugs to cancer cells while minimizing effects on normal tissues.

Two specific ADCs targeting FcRL5 demonstrated significant efficacy in both laboratory and animal models, especially when used in combination with existing myeloma treatments like bortezomib or lenalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. Elkins, K., Zheng, B., Go, M., et al.[2020]

Daratumumab (DARA), a therapeutic antibody targeting CD38, can induce programmed cell death in multiple myeloma cells when cross-linked by secondary antibodies or Fcγ receptors, highlighting its potential effectiveness in treating this cancer.

In both in vitro and in vivo studies, the activation of both inhibitory and activating Fcγ receptors was shown to facilitate this cell death, suggesting that FcγR-mediated cross-linking is a key mechanism contributing to the therapeutic activity of DARA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Therapeutic CD38 Monoclonal Antibody Daratumumab Induces Programmed Cell Death via Fcγ Receptor-Mediated Cross-Linking. Overdijk, MB., Jansen, JH., Nederend, M., et al.[2022]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Daratumumab, an anti-CD38 antibody, shows strong anti-tumor activity in various types of non-Hodgkin lymphoma (NHL), including mantle cell lymphoma (MCL) and follicular lymphoma (FL), both in laboratory models and in vivo, effectively preventing tumor growth and improving overall survival.

The drug enhances the effectiveness of standard chemotherapy regimens (CHOP and R-CHOP) in treating MCL and FL, demonstrating its potential as a valuable addition to existing therapies for these lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens. Vidal-Crespo, A., Matas-Céspedes, A., Rodriguez, V., et al.[2022]

Denosumab is a new bone-protective agent that has been shown to be more effective than the previously standard treatment, zoledronic acid, in managing skeletal-related events in patients with castration-resistant prostate cancer (CRPC).

The review also evaluates the cost-effectiveness of denosumab, highlighting its similar rate of adverse effects compared to zoledronic acid, making it a favorable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of denosumab as a bone protective agent for patients with castration resistant prostate cancer. Dellis, A., Papatsoris, A.[2018]

In a phase III trial involving 462 patients with metastatic renal cell carcinoma, Rocapuldencel-T combined with standard treatment did not significantly improve overall survival compared to standard treatment alone, with median overall survival of 27.7 months for the combination group versus 32.4 months for the standard treatment group.

Despite the lack of overall survival benefit, 70% of patients receiving Rocapuldencel-T showed immune responses, which correlated positively with overall survival, suggesting that while the therapy may not extend life, it can stimulate the immune system in a meaningful way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma. Figlin, RA., Tannir, NM., Uzzo, RG., et al.[2021]

In a study of 40 men with hormone refractory prostate cancer, the combination of docetaxel, vinorelbine, and zoledronic acid showed promising results, with 18% achieving complete PSA responses and 32% showing major PSA responses after treatment.

The treatment was well tolerated, with manageable side effects; the median overall survival was 17 months, and nearly half of the patients experienced a reduction in pain intensity and analgesic use after two cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel, vinorelbine, and zoledronic acid as first-line treatment in patients with hormone refractory prostate cancer: a phase II study. Di Lorenzo, G., Autorino, R., Perdonà, S., et al.[2018]

The treatment landscape for castration-resistant prostate cancer (CRPC) has expanded significantly in the last two years, with four new approved drugs and an upcoming immunotherapy option, sipuleucel-T, enhancing treatment options beyond traditional chemotherapy with docetaxel.

For asymptomatic or minimally symptomatic CRPC patients who have not undergone chemotherapy, the androgen biosynthesis inhibitor abiraterone has demonstrated a significant survival benefit, while other treatments like enzalutamide and cabazitaxel have shown effectiveness for patients whose disease has progressed after docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapy concepts for castration-resistant prostate cancer: between hormone manipulation, targeted therapy and chemotherapy]. Kübler, H., Miller, K.[2021]

The study found that dendritic cell (DC)-tumor fusion vaccines are more effective than traditional DC vaccines sensitized with tumor lysates in treating hormone-refractory prostate cancer (HRPC), as indicated by higher levels of IL-12 and interferon-gamma production.

In functional assays, T cells activated by the DC-tumor fusion vaccine demonstrated significantly greater tumor-killing activity compared to those activated by DCs pulsed with tumor lysates, suggesting enhanced efficacy of the fusion vaccine approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The establishment of dendritic cell-tumor fusion vaccines for hormone refractory prostate cancer cell. Kim, TB., Park, HK., Chang, JH., et al.[2021]

References

1. China pubmed.ncbi.nlm.nih.gov

Expanded natural killer cells augment the antimyeloma effect of daratumumab, bortezomib, and dexamethasone in a mouse model. [2023]

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

FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. [2020]

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

The Therapeutic CD38 Monoclonal Antibody Daratumumab Induces Programmed Cell Death via Fcγ Receptor-Mediated Cross-Linking. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

5. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab displays in vitro and in vivo anti-tumor activity in models of B-cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of denosumab as a bone protective agent for patients with castration resistant prostate cancer. [2018]

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

Results of the ADAPT Phase 3 Study of Rocapuldencel-T in Combination with Sunitinib as First-Line Therapy in Patients with Metastatic Renal Cell Carcinoma. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Docetaxel, vinorelbine, and zoledronic acid as first-line treatment in patients with hormone refractory prostate cancer: a phase II study. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

[New therapy concepts for castration-resistant prostate cancer: between hormone manipulation, targeted therapy and chemotherapy]. [2021]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

The establishment of dendritic cell-tumor fusion vaccines for hormone refractory prostate cancer cell. [2021]