Avelumab + Lenvatinib for Brain Cancer

Not currently recruiting at 16 trial locations

Overseen By US Medical Information

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: EMD Serono Research & Development Institute, Inc.

Must not be taking: Antiepileptics

Disqualifiers: Low-grade gliomas, Uncontrolled seizures, Bulky tumor, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for brain cancer using two drugs: Avelumab (an immunotherapy drug) and Lenvatinib (a targeted therapy drug). The goal is to determine the safest dose and assess its effectiveness in preventing cancer progression. Ideal participants are those with specific aggressive brain tumors who have not responded to other treatments. This study provides an opportunity to try a new approach that might slow tumor growth. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, allowing participants to be among the first to receive this new combination.

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.

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

Research has shown that the combination of Avelumab and Lenvatinib has been tested for safety in other studies. Trials have used Avelumab for bladder cancer, finding it safe with positive results. When Lenvatinib was combined with another drug, dose adjustments were sometimes necessary due to side effects, but these changes effectively managed the side effects.

In other studies, Avelumab combined with different drugs was generally well-tolerated. Safety data from these studies suggest that the combination of Avelumab and Lenvatinib is manageable, though some patients might experience side effects that require monitoring.

As this trial is in an early phase, it focuses on ensuring the treatment's safety and determining the right dose. This involves close monitoring and adjustments to keep side effects manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Avelumab + Lenvatinib for brain cancer because it offers a new approach by combining an immune checkpoint inhibitor with a targeted therapy. Avelumab works by blocking a protein that tumors use to hide from the immune system, potentially boosting the body's ability to attack cancer cells. Lenvatinib, on the other hand, inhibits specific enzymes that tumors need to grow new blood vessels, effectively starving the tumor. This combination could provide a more comprehensive attack on the cancer, which is different from existing treatments like surgery, radiation, or chemotherapy that often focus on just one aspect of tumor control.

What evidence suggests that Avelumab and Lenvatinib might be an effective treatment for brain cancer?

This trial will evaluate the combination of avelumab and lenvatinib for treating brain cancer. Research suggests that using these drugs together may help treat certain cancers. Avelumab boosts the immune system's ability to attack cancer cells and has shown positive results when combined with brain radiation therapy. Lenvatinib, another cancer-fighting drug, has been effective in treating kidney cancer, though its dose may require adjustment due to side effects. Together, these drugs might enhance the body's immune response and slow tumor growth, showing potential for treating brain cancer. While research continues, early results indicate this combination could be promising for treating tumors in the central nervous system. ^{1 3 4 6 7}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Are You a Good Fit for This Trial?

This trial is for children with confirmed primary CNS tumors who meet specific criteria based on tumor type and previous treatments. They must have measurable disease, be able to perform daily activities at a certain level (Lansky or Karnofsky performance status >= 50), and not have had major surgery or intracranial hemorrhage recently.

Inclusion Criteria

Other protocol defined inclusion criteria could apply

I have a high-grade brain tumor and have had at least one treatment, or I have a specific type of brain tumor (diffuse midline glioma) and may have had up to one treatment or just radiotherapy.

On screening scans, measurable disease by RANO criteria

Exclusion Criteria

Other protocol defined exclusion criteria could apply

My tumor is large or causing significant pressure inside my brain.

My seizures are under control and do not affect my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Part 1

Evaluate the safety and tolerability of Avelumab in combination with Lenvatinib and determine the recommended dose for expansion

Dose Expansion Part 2

Assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary CNS tumors

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab
• Lenvatinib

Trial Overview The study tests Avelumab combined with Lenvatinib in two parts: first, finding the safest dose combination (Dose Escalation Part 1), then checking how well it works to stop tumor growth without worsening (Dose Expansion Part 2) by measuring progression-free survival.

How Is the Trial Designed?

Group I: Avelumab + Lenvatinib Experimental Treatment 2 Interventions

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

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Published Research Related to This Trial

In a phase 2 study involving 54 patients with advanced endometrial cancer, the combination of lenvatinib and pembrolizumab resulted in a 39.6% objective response rate at week 24, indicating significant anti-tumor activity.

The treatment was generally well-tolerated, with serious adverse events occurring in 30% of patients, including one treatment-related death; however, the safety profile was consistent with previous studies of the individual drugs, except for a higher incidence of hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Makker, V., Rasco, D., Vogelzang, NJ., et al.[2020]

The maximum tolerated dose (MTD) of lenvatinib when combined with carboplatin and paclitaxel for treating advanced non-small-cell lung cancer (NSCLC) is established at 4 mg taken twice daily, showing manageable side effects.

The treatment regimen resulted in a response rate of 68% and a median progression-free survival of 9.0 months, indicating promising antitumor activity in chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. Nishio, M., Horai, T., Horiike, A., et al.[2021]

The combination of lenvatinib and pembrolizumab shows significant clinical benefits for patients with endometrial carcinoma, with a safety profile consistent with each drug's individual use, primarily involving manageable side effects like hypertension and hypothyroidism.

Effective management of lenvatinib's common adverse events is crucial to maximize its efficacy, as most side effects can be prevented or mitigated through proactive monitoring and intervention during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. Lorusso, D., Danesi, R., Locati, LD., et al.[2023]

In a phase 1 study involving 27 patients, lenvatinib treatment led to significant tumor shrinkage, which correlated with changes in plasma angiogenic biomarkers such as increased VEGF and SDF1α levels and decreased sVEGFR2 levels.

Adverse events like hypertension and proteinuria were also linked to changes in these biomarkers, suggesting that monitoring plasma angiogenic proteins could help predict lenvatinib's efficacy and side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1 study of the multi-kinase inhibitor lenvatinib. Koyama, N., Saito, K., Nishioka, Y., et al.[2021]

Lenvatinib, a multitargeted Tyrosine Kinase Inhibitor, has shown significant improvement in Progression-Free Survival (PFS) for patients with aggressive Differentiated Thyroid Cancer (DTC) not responsive to radioiodine, with a median PFS of 18.2 months compared to 3.6 months for placebo.

While lenvatinib is effective, it is associated with a high rate of adverse effects (over 40%), including hypertension and fatigue, and about 14% of patients may need to discontinue treatment due to these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied. Ferrari, SM., Ruffilli, I., Centanni, M., et al.[2018]

The combination of lenvatinib, a multikinase inhibitor, and pembrolizumab, a PD-1 inhibitor, shows promising antitumor activity and durable responses in various solid tumors, as indicated by preliminary results from the LEAP clinical trial program.

This combination therapy has a manageable safety profile, suggesting it could be a valuable new treatment option for solid cancers that currently have limited therapeutic alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

In a study involving 137 patients with advanced solid tumors, the combination of lenvatinib and pembrolizumab showed a manageable safety profile, with common side effects including fatigue, diarrhea, and hypertension.

The treatment demonstrated promising antitumor activity, with objective response rates at week 24 ranging from 25% to 63% across different cancer types, indicating its potential effectiveness in various advanced cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. Taylor, MH., Lee, CH., Makker, V., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05081180

Study of Avelumab in Combination With Lenvatinib for ... Dose Expansion Part 2 will assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11789451/

Clinical outcomes by baseline metastases in patients with ... We report results of an exploratory post hoc analysis of tumor response data based on baseline metastatic characteristics of patients who received lenvatinib ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2949820125000311

Effectiveness, toxicity and treatment adjustments of ... Lenvatinib plus pembrolizumab is effective in RCC outside of clinical trials. A large subset of patients required treatment adjustments due to AEs.

4. academic.oup.com academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noaf183/8245008

Phase IB study of Avelumab and whole brain radiotherapy in ... Correlative studies showed Avelumab + WBRT to stimulate an adaptive immune response in the CSF space. Results were encouraging and serve as a ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8633738/

Emergent immunotherapy approaches for brain metastases Emerging immunotherapy approaches will have to focus on increasing response rates, decreasing toxicity, and decreasing steroid dependency.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11764420/

Real-World Efficacy and Safety of Avelumab Plus Axitinib ... This trial revealed that patients treated with the combination exhibited a significantly improved objective response rate (ORR) and progression- ...

7. onclive.com onclive.com/view/real-world-data-support-the-frontline-use-of-avelumab-plus-axitinib-in-advanced-rcc

Real-World Data Support the Frontline Use of Avelumab ... The AVION study confirmed the real-world effectiveness and safety of avelumab plus axitinib in advanced RCC, with a 12-month OS rate of 82.7%.