A Study of Lenvatinib for Pediatric Patients with Relapsed or Refractory Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

13 Jul 2020 → 13 Feb 2025

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · Eisai Co., Ltd.

External identifiers

EU CT number

2024-512135-80-00

EudraCT number

2019-004441-33

WHO UTN

U1111-1304-6856

ClinicalTrials.gov

NCT04447755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Pharmacogenomic, Efficacy, Pharmacodynamic, Pharmacokinetic, Therapy, Safety

To determine the Objective Response Rate (ORR) at Week 16, by each tumor type, per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) (for High Grade Glioma [HGG] only) as assessed by the investigator.

Secondary objectives 6

1. 1. To evaluate ORR, by each tumor type, per RECIST 1.1 or RANO (for HGG only) as assessed by the investigator.
2. 2. To evaluate Progression-free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by each tumor type.
3. 3. To evaluate the Best Overall Response (BOR), Duration of Response (DOR), Disease Control Rate (DCR), and Clinical Benefit Rate (CBR) by each tumor type.
4. 4. To evaluate the safety of lenvatinib (MK-7902).
5. 5. To assess the palatability and acceptability of the suspension formulation of lenvatinib.
6. 6. To characterize the pharmacokinetics (PK) of lenvatinib.

Conditions and MedDRA coding

Between ages 2 and 21 and have High Grade Glioma (HGG), Rhabdomyosarcoma (RMS), Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (pPNET), or other solid tumor types (except osteosarcoma)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001119-PIP03-19

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Has histologically or cytologically documented relapsed, or refractory pediatric solid malignancy excluding osteosarcoma
2. 2. Has measurable disease as defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for High Grade Glioma (HGG)
3. 3. Has a performance status defined as follows: 1) Lansky Play Score ≥50 for participants up to and including 16 years of age 2) Karnofsky performance status (KPS) ≥50 for participants >16 years of age 3) Neurologic deficits in participants with primary central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment
4. 4. Demonstrate adequate organ function
5. 5. No clinical evidence of nephrotic syndrome.
6. 6. Has adequate blood pressure (BP) control with or without antihypertensive medications
7. 7. Has adequate cardiac function
8. 8. Has adequate neurologic function
9. 9. Participant must have fully recovered to Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) Grade ≤1 (except for alopecia, ototoxicity, and Grade ≤2 peripheral neuropathy) from the acute toxic effects of all prior anticancer therapy
10. 10. Male participants must agree to use approved contraception during the treatment period and for at least 7 days after the last dose of study intervention and refrain from donating sperm during this period

Exclusion criteria 17

1. 1. Has had major surgery within 3 weeks prior to Cycle 1 Day 1 (C1D1)
2. 2. Has gastrointestinal (GI) bleeding or active hemoptysis (bright red blood of at least half teaspoon) within 21 days prior to enrollment
3. 3. Has CNS tumors with a history of symptomatic tumor hemorrhage
4. 4. Has evidence of new intracranial hemorrhage of more than punctate size on MRI assessment obtained within 28 days prior to study enrollment
5. 5. Has radiographic evidence of encasement or invasion of a major blood vessel or of intratumoral cavitation
6. 6. Has evidence of untreated CNS metastases (exception: participants with primary CNS tumors and leptomeningeal disease.
7. 7. Has GI malabsorption, GI anastomosis, or any other condition that in the opinion of the investigator might affect the absorption of lenvatinib
8. 8. Has preexisting ≥Grade 3 GI or non-GI fistula
9. 9. Has any active infection requiring systemic therapy
10. 10. Known to be Human immunodeficiency virus (HIV) positive
11. 11. Known active viral hepatitis (B or C) as demonstrated by positive serology. Testing for hepatitis B or hepatitis C is required at screening only when mandated by local health authority
12. 12. Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the date of allocation
13. 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
14. 14. Has known hypersensitivity to any component of the investigational product (lenvatinib or ingredients)
15. 15. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the stud
16. 16. Has clinically significant cardiovascular disease within 6 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
17. 17. Has non-healing wound, tumor ulceration, unhealed or incompletely healed fracture, or a compound (open) bone fracture at the time of enrollment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Objective Response Rate (ORR) At Week 16 per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria (for High Grade Glioma [HGG] only), by Investigator Assessment

Secondary endpoints 10

1. 1. ORR per RECIST 1.1 or RANO Criteria (for HGG only), by Investigator Assessment
2. 2. Progression Free Survival (PFS) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
3. 3. Best Overall Response (BOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
4. 4. Duration of Response (DOR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
5. 5. Disease Control Rate (DCR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
6. 6. Clinical Benefit Rate (CBR) per RECIST 1.1 or RANO (for HGG only), by Investigator Assessment
7. 7. Number of Participants who Experience an Adverse Event (AE)
8. 8. Number of Participants who Discontinue Study Treatment Due to an AE
9. 9. Palatability Questionnaire Score For Lenvatinib Suspension Formulation
10. 10. Area Under the Concentration-Time Curve of lenvatinib From Time 0 to Infinity (AUC 0-inf)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Behzad Bidadi

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Behzad Bidadi

Third parties 5

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications