Efineptakin Alfa + Pembrolizumab for Glioblastoma

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Bevacizumab, Live vaccines, Dexamethasone

Disqualifiers: HIV, Active autoimmune, Hepatitis B/C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 45

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether two drugs, efineptakin alfa and pembrolizumab, can safely treat glioblastoma, a type of brain cancer that has recurred after treatment. Efineptakin alfa boosts the immune system to attack cancer cells, while pembrolizumab may help prevent tumor growth and spread. Individuals with recurrent glioblastoma who have previously undergone surgery, radiation, and chemotherapy might be suitable candidates, especially if they are willing to undergo surgery again at Mayo Clinic in Rochester, Minnesota. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial information does not specify if you need to stop taking your current medications. However, certain medications like bevacizumab and live vaccines have specific restrictions before joining. 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 has shown that the drugs efineptakin alfa and pembrolizumab may help treat recurring glioblastoma, a type of brain cancer. The FDA has granted efineptakin alfa "orphan drug" status for glioblastoma, indicating potential important benefits, although its safety is still under investigation.

For pembrolizumab, studies have found that patients with glioblastoma generally tolerate it well. Some side effects have been reported, but they are usually manageable. Both treatments are still undergoing clinical trials to better understand their safety.

This trial is in Phase 2, indicating some evidence of safety, but more information is needed for confirmation. Participants should discuss the possible risks and benefits with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using efineptakin alfa with pembrolizumab for glioblastoma because this combination offers a new approach to tackling this aggressive brain cancer. Unlike standard treatments like temozolomide and radiation, which primarily focus on directly attacking tumor cells, efineptakin alfa boosts the immune response by increasing the activity of certain immune cells, potentially enhancing the effects of pembrolizumab, an immune checkpoint inhibitor. This combination aims to not only target the tumor but also strengthen the body's own defenses, which could lead to more effective and lasting control of the disease.

What evidence suggests that efineptakin alfa and pembrolizumab might be effective for glioblastoma?

Research has shown that combining efineptakin alfa with pembrolizumab may help treat recurrent glioblastoma by boosting the immune system. In this trial, participants will receive both efineptakin alfa and pembrolizumab. Efineptakin alfa increases CD8 T cells, which can attack cancer cells, and reduces T-regulatory cells that often weaken the immune response. In animal studies, this combination showed promise in slowing tumor growth. Pembrolizumab, a monoclonal antibody, helps the immune system better recognize and fight cancer cells. Together, these treatments aim to improve the body's ability to find and destroy tumor cells in glioblastoma patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Jian L. Campian, MD, PhD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults with recurrent Grade IV glioblastoma, previously treated with surgery, radiation, and temozolomide. Participants must have good organ function, be willing to provide tissue samples, and agree to use contraception if they can have children. Excluded are those on other trials, pregnant or nursing individuals, people needing high-dose steroids or with severe diseases that could interfere with the trial.

Inclusion Criteria

I am willing to have surgery or a biopsy at Mayo Clinic in Rochester.

Willing to use contraception

Absolute neutrophil count (ANC) >= 1500/mm^3

Exclusion Criteria

I do not have any unmanaged ongoing illnesses.

I haven't needed systemic treatment for cancer in the last year.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Surgery Treatment

Participants receive pembrolizumab IV and efineptakin alfa IM on day 1, followed by surgery 1 week later

1 week

1 visit (in-person)

Post-Surgery Treatment

Participants receive pembrolizumab IV and efineptakin alfa IM on day 1 of each cycle, with cycles repeating every 42 days for up to 2 years

Up to 2 years

Every 42 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 days, every 2-3 months until disease progression, and then every 6 months for up to 5 years

Up to 5 years

Every 2-3 months, then every 6 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Efineptakin alfa
• Pembrolizumab

Trial Overview The trial is testing efineptakin alfa combined with pembrolizumab in patients whose glioblastoma has returned. Efineptakin alfa boosts the immune system's ability to fight cancer cells while pembrolizumab may prevent tumor growth by helping the immune system attack cancer.

How Is the Trial Designed?

Group I: Treatment (efineptakin alfa, pembrolizumab) Experimental Treatment 4 Interventions

BEFORE SURGERY: Patients receive pembrolizumab IV over 30 minutes and efineptakin alfa IM on day 1. Patients then undergo surgery 1 week later. AFTER SURGERY: Patients receive pembrolizumab IV over 30 minutes and efineptakin alfa IM on day 1 of each cycle. Cycles repeat every 42 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo MRI or CT at baseline and on study. Patients also undergo tumor biopsy at baseline and blood sample collection on study.

Efineptakin alfa is already approved in United States for the following indications:

Approved in United States as Efineptakin alfa for:

• Orphan drug designation for pancreatic cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

NeoImmune Tech

Collaborator

Trials

4

Recruited

250+

NeoImmuneTech

Industry Sponsor

Trials

16

Recruited

780+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase III trial involving 639 patients with newly diagnosed glioblastomas (GBMs) that have EGFR gene amplification, depatuxizumab mafodotin (depatux-m) did not improve overall survival compared to placebo, with median survival times of 18.9 months for depatux-m and 18.7 months for placebo.

However, depatux-m did show a significant improvement in progression-free survival, particularly in patients with the EGFRvIII mutation and unmethylated MGMT tumors, indicating potential benefits in delaying disease progression despite no overall survival advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial. Lassman, AB., Pugh, SL., Wang, TJC., et al.[2023]

In a study involving 260 patients with recurrent EGFR-amplified glioblastoma, the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M) did not improve health-related quality of life (HRQoL) or neurological deterioration-free survival (NDFS) compared to standard treatments like temozolomide or lomustine.

Patients receiving Depatux-M experienced significant visual disorders, which were clinically relevant and consistent with known side effects of the drug, highlighting a safety concern despite the lack of overall survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma. Clement, PMJ., Dirven, L., Eoli, M., et al.[2021]

In a study of 28 heavily pretreated patients with recurrent malignant gliomas, the combination of EGFR inhibitors (gefitinib or erlotinib) and the mTOR inhibitor sirolimus was reasonably well tolerated, indicating a favorable safety profile for this treatment approach.

The treatment resulted in a 19% partial response rate and 50% of patients achieving stable disease, with a 25% six-month progression-free survival rate specifically for glioblastoma patients, suggesting potential efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas. Doherty, L., Gigas, DC., Kesari, S., et al.[2022]

The novel immunotoxin D2C7-(scdsFv)-PE38KDEL effectively targets both the wild-type epidermal growth factor receptor (EGFR) and the EGFR deletion mutant (EGFRvIII), which are commonly found in glioblastoma.

This immunotoxin has shown strong anti-cancer effects in established murine glioma models, indicating its potential as a therapeutic option for treating this aggressive brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel recombinant immunotoxin-based therapy targeting wild-type and mutant EGFR improves survival in murine models of glioblastoma. Chandramohan, V., Bigner, DD.[2022]

In a study of 66 patients with recurrent glioblastoma (rGBM) and EGFR amplification, depatuxizumab mafodotin (depatux-m) showed a 6-month progression-free survival rate of 28.8% and an overall survival rate of 72.5%, indicating potential efficacy in this difficult-to-treat population.

The treatment was associated with frequent ocular adverse events, primarily Grade 1/2, such as blurred vision and dry eye, but these were manageable and typically resolved after stopping the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of depatuxizumab mafodotin (ABT-414) monotherapy in patients with EGFR-amplified, recurrent glioblastoma: results from a multi-center, international study. van den Bent, M., Gan, HK., Lassman, AB., et al.[2021]

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

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 phase II study involving 80 patients with recurrent glioblastoma, pembrolizumab combined with bevacizumab showed a 6-month progression-free survival (PFS-6) of 26% and a median overall survival (OS) of 8.8 months, indicating limited efficacy despite being well tolerated.

Pembrolizumab alone had a much lower PFS-6 of 6.7% and no objective responses, suggesting that while the combination therapy had some durable responses, neither treatment was effective enough for significant clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Nayak, L., Molinaro, AM., Peters, K., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

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Efineptakin Alfa and Pembrolizumab for the Treatment of ... This phase II trial tests the safety and side effects of efineptakin alfa and pembrolizumab in treating patients with glioblastoma that has come back ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10640202/

CTIM-33. EFFICACY AND SAFETY STUDY ... Efineptakin alfa (NT-I7), a long-acting IL-7, has been shown to increase effector CD8 T cells and reduce suppressor T-regulatory cells in murine GBM models, ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20534587

Efineptakin alfa (NT-I7) Plus Pembrolizumab for the ... The purpose of this study is to determine the response rate to the combination of pembrolizumab and NT-I7 in patients with recurrent glioblastoma.

4. trialx.com trialx.com/clinical-trials/listings/230645/efineptakin-alfa-and-pembrolizumab-for-the-treatment-of-recurrent-glioblastoma/

Efineptakin Alfa and Pembrolizumab for the Treatment of ... Giving efineptakin alfa and pembrolizumab may kill more tumor cells in patients with recurrent glioblastoma. Description. PRIMARY OBJECTIVE: I.

5. asco.org asco.org/abstracts-presentations/ABSTRACT215885

Window-of-opportunity clinical trial of a PD-1 inhibitor in ... Background: A Phase III study failed to demonstrate a therapeutic benefit of anti-PD-1 therapy in recurrent GBM. This study was initiated to ascertain tumor ...

6. onclive.com onclive.com/view/fda-grants-orphan-drug-designation-to-nt-i7-for-glioblastoma-multiforme

FDA Grants Orphan Drug Designation to NT-I7 ... - OncLive The FDA has granted an orphan drug designation (ODD) to NT-I7 (efineptakin alfa; rhIL-7-hyFc; GX-I7) for the treatment of patients with glioblastoma multiforme.

7. targetedonc.com targetedonc.com/view/fda-grants-orphan-drug-designation-to-nt-i7-for-glioblastoma-multiforme

FDA Grants Orphan Drug Designation to NT-I7 for ... Preliminary data from the NIT-107 trial showed favorable trends in PFS and overall survival (OS) in patients who received NT-I7 following ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.2040

A phase I/II study to evaluate the safety and efficacy of ... NT-I7 (efineptakin alfa) is the first-in-class long-acting recombinant human IL-7 that supports proliferation and survival of CD4+ and CD8+ T- ...