Daratumumab + Radiation/Temozolomide for Glioblastoma

(PRIDE Trial)

Overseen By Sonikpreet Aulakh, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: West Virginia University

Must not be taking: BCG, Deferiprone, Dipyrone, others

Disqualifiers: Prior GBM treatment, Uncontrolled illness, 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: 9

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding Daratumumab (also known as Darzalex, Darzalex SC, or Darzalex Faspro) to the usual treatment for glioblastoma (a type of brain cancer) can enhance its effectiveness. Glioblastoma is challenging to treat, and researchers aim to determine if Daratumumab can more effectively kill cancer cells when combined with standard therapies like radiation and Temozolomide (a chemotherapy drug). Suitable candidates for this trial are those diagnosed with glioblastoma who have not yet received treatment. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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

The trial protocol does not specify if you need to stop your current medications. However, certain drugs, especially those in risk categories X, D, and C, should be avoided or monitored when used with Daratumumab and TMZ. It's best to discuss your current medications with the trial team.

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

Research shows that Daratumumab is usually well-tolerated when combined with other treatments. Studies have found that patients using a form of Daratumumab for multiple myeloma generally experienced few serious side effects, indicating a good safety record. The FDA has reviewed Daratumumab and determined that its benefits outweigh its risks for certain conditions.

Although Daratumumab is mainly used for other diseases, its safety in those cases provides some confidence about its use in this new trial. However, since this trial is in the early stages, monitoring patient responses closely when combined with glioblastoma treatments is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for glioblastoma, which typically include surgery, radiation, and chemotherapy with temozolomide, daratumumab offers a novel approach. Daratumumab is a monoclonal antibody that specifically targets CD38, a protein found on the surface of certain tumor cells, potentially leading to direct cancer cell death. Researchers are excited about this treatment because it introduces a new mechanism of action that could enhance the body's immune response against the tumor. By combining daratumumab with traditional therapies, there's hope for improved outcomes in a condition known for its aggressive nature and limited treatment success.

What evidence suggests that Daratumumab might be an effective treatment for glioblastoma?

Research has shown that Daratumumab can help treat certain cancers by aiding the immune system in attacking cancer cells. In other studies, it significantly improved treatment results, with 63.4% of patients responding well compared to only 2.0% with regular monitoring. This suggests that Daratumumab can be very effective in fighting cancer. The treatment has also demonstrated great results when combined with other therapies. Specifically, 91% of patients responded well when Daratumumab was used alongside other cancer treatments. This trial will evaluate the effectiveness of adding Daratumumab to the usual glioblastoma treatment, which could potentially enhance treatment outcomes. ^{1 3 6 7 8}

Who Is on the Research Team?

Sonikpreet Aulakh, MD

Principal Investigator

WVU Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with glioblastoma (GBM) who haven't had prior treatment for it. They must be in good general health with proper organ and marrow function, not have severe illnesses or psychiatric conditions that could affect participation, and agree to use contraception. People with certain heart diseases, uncontrolled asthma, COPD, or a history of allergic reactions to similar drugs are excluded.

Inclusion Criteria

I agree to use birth control during the study.

My blood tests show normal organ function and I don't have severe kidney issues.

I have chronic hepatitis B but it's under control with treatment.

Exclusion Criteria

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

Patients receiving any other investigational agents

I have received treatment for brain cancer before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery/Biopsy

Participants receive one dose of Daratumumab prior to surgery or biopsy

1 week

1 visit (in-person)

Treatment

Participants receive Daratumumab in combination with Temozolomide and radiation therapy

24 weeks

Weekly visits for 8 weeks, then bi-weekly visits until week 24

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab

Trial Overview The study tests if adding Daratumumab to the standard GBM therapy of Temozolomide (TMZ) and radiation can better kill cancer cells. It's divided into two parts: an initial phase I with up to 6 participants followed by a phase II involving 10-13 more subjects.

How Is the Trial Designed?

Group I: Daratumumab Experimental Treatment 1 Intervention

Daratumumab, IV, 16 mg/KG - 1 dose prior to surgery or biopsy; Weeks 1 - 8 = 1 dose weekly; Weeks 9 - 24 = 1 dose every other week; Weeks 25 onward (determined by disease progression) = 1 dose every 4 weeks

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Published Research Related to This Trial

Depatuxizumab mafodotin (depatux-m) has an acceptable safety profile, with ocular toxicities being the most common side effects observed in 92% of patients, and a maximum tolerated dose of 1.5 mg/kg established for its combination with temozolomide.

In patients with recurrent glioblastoma, depatux-m showed promising preliminary efficacy, with a 6-month progression-free survival rate of 30.8% and a median overall survival of 10.7 months, indicating potential benefits for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma. Gan, HK., Reardon, DA., Lassman, AB., et al.[2023]

Adding nitrosourea-based chemotherapy to radiotherapy has been shown to increase progression-free survival in patients with grade II and III gliomas, although it does not improve overall survival.

Upcoming phase III trials will investigate whether adding temozolomide to radiotherapy can enhance overall survival in grade II/III gliomas, while also assessing cognitive function and quality of life for better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and radiation in low-grade and anaplastic gliomas: temoradiation. Schiff, D.[2018]

Nivolumab combined with radiotherapy and temozolomide (NIVO+RT+TMZ) is tolerable for patients with newly diagnosed glioblastoma, with no new safety concerns identified; however, higher rates of grade 3/4 treatment-related adverse events were observed compared to Nivolumab with radiotherapy alone (NIVO+RT).

The study found that overall survival (OS) was similar for patients with unmethylated MGMT promoter whether they received NIVO+RT+TMZ or NIVO+RT, indicating that the addition of temozolomide may not significantly improve outcomes in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. Omuro, A., Reardon, DA., Sampson, JH., et al.[2023]

In a retrospective analysis of the AVAglio trial involving 921 glioblastoma patients, those with IDH1 wild-type proneural tumors showed a significant overall survival (OS) benefit from bevacizumab treatment compared to placebo, with an OS of 17.1 months versus 12.8 months.

While patients with mesenchymal and proneural tumors experienced progression-free survival (PFS) benefits from bevacizumab, only the proneural subtype demonstrated a corresponding OS advantage, highlighting the importance of molecular subtypes in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients With Proneural Glioblastoma May Derive Overall Survival Benefit From the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial. Sandmann, T., Bourgon, R., Garcia, J., et al.[2022]

The combination of anti-GITR monoclonal antibody (mAb) and stereotactic radiosurgery (SRS) significantly improved survival rates in a mouse model of glioblastoma, with a cure rate of 24% compared to 0% for either treatment alone, indicating a strong immune-mediated effect.

The treatment with anti-GITR (1) and SRS led to increased infiltration of CD4+ effector T-cells and enhanced production of immune signaling molecules like IFNγ and IL-2, suggesting that this combination effectively shifts the immune response against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma. Patel, MA., Kim, JE., Theodros, D., et al.[2022]

Citations

1. onclive.com onclive.com/view/daratumumab-significantly-improves-pfs-extends-os-in-smoldering-myeloma

Daratumumab Significantly Improves PFS, Extends OS in ... Daratumumab generated a superior overall response rate of 63.4% compared with 2.0% with active monitoring, indicating its efficacy.

2. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

3. cancernetwork.com cancernetwork.com/view/odac-votes-6-2-for-benefit-risk-profile-of-sq-daratumumab-in-high-risk-smoldering-multiple-myeloma

ODAC Votes 6-2 For Benefit-Risk Profile of SQ ... With a median follow-up of 65.2 months (range, 0-76.6), 34.5% of patients in the daratumumab group and 50.5% of patients in the active ...

4. darzalex.com darzalex.com/clinical-results/

Clinical Results 91% (about 9 of 10) of patients responded to treatment with DARZALEX FASPRO ® in combination with lenalidomide and dexamethasone (DRd).

5. oncnursingnews.com oncnursingnews.com/view/subcutaneous-daratumumab-could-mark-first-smoldering-myeloma-treatment

Subcutaneous Daratumumab Could Mark First Smoldering ... At 60 months, overall survival rates were 93.0% and 86.9% in the daratumumab and active monitoring arms, respectively, ultimately reducing the ...

6. onclive.com onclive.com/view/fda-s-odac-votes-in-favor-of-risk-benefit-profile-of-subcutaneous-daratumumab-for-high-risk-smoldering-myeloma

FDA's ODAC Votes in Favor of Risk/Benefit Profile ... The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 6 to 2 in favor of the risk/benefit profile of subcutaneous daratumumab.

7. darzalexhcp.com darzalexhcp.com/

HCP Website | DARZALEX® (daratumumab) & DARZALEX ... The hazard ratio was 0.55 with a 95% confidence interval that ranged from 0.45 to 0.67. ... This translates to a 45% risk reduction for disease progression or ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141371/

Real-world data on the use of subcutaneous daratumumab ... Here we present findings from a noninterventional, multicenter study assessing the safety and clinical outcomes of daratumumab SC plus VTd ( ...