17 Participants Needed

Avelumab + Lenvatinib for Brain Cancer

Recruiting at 9 trial locations
CC
UM
Overseen ByUS Medical Information
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: EMD Serono Research & Development Institute, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

This study consists of 2 parts: Dose Escalation Part 1 and Dose Expansion Part 2. The Dose Escalation Part 1 will evaluate the safety and tolerability of Avelumab in combination with Lenvatinib and determine the recommended Avelumab and Lenvatinib dose for expansion. Dose Expansion Part 2 will assess the efficacy of Avelumab in combination with Lenvatinib by Progression-free Survival in participants with pre-defined primary central nervous system (CNS) tumors.

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.

What safety data exists for Avelumab and Lenvatinib in humans?

Lenvatinib has been studied in combination with other drugs for various cancers, showing a manageable safety profile. Common side effects include high blood pressure, low thyroid function, diarrhea, nausea, vomiting, loss of appetite, fatigue, and weight loss.12345

How is the drug Avelumab + Lenvatinib unique for treating brain cancer?

Avelumab + Lenvatinib is unique because it combines an immune checkpoint inhibitor (Avelumab) with a multikinase inhibitor (Lenvatinib) that targets multiple pathways involved in tumor growth and blood vessel formation, potentially enhancing the immune system's ability to fight cancer. This combination approach is novel for brain cancer, where standard treatments are limited.34678

Research Team

MR

Medical Responsible

Principal Investigator

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

Eligibility Criteria

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
See 1 more

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.
See 4 more

Timeline

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

Treatment Details

Interventions

  • Avelumab
  • Lenvatinib
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Avelumab + LenvatinibExperimental Treatment2 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

Find a Clinic Near You

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 profile image

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo profile image

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Findings from Research

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.
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.
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma.Lorusso, D., Danesi, R., Locati, LD., et al.[2023]
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.
The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors.Taylor, MH., Schmidt, EV., Dutcus, C., et al.[2021]

References

Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer. [2021]
Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma. [2023]
The LEAP program: lenvatinib plus pembrolizumab for the treatment of advanced solid tumors. [2021]
4.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Lenvatinib in the Therapy of Aggressive Thyroid Cancer: State of the Art and New Perspectives with Patents Recently Applied. [2018]
Lenvatinib in combination with everolimus in patients with advanced or metastatic renal cell carcinoma: A phase 1 study. [2019]
Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. [2020]
Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. [2021]
Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1 study of the multi-kinase inhibitor lenvatinib. [2021]