Clinical Trial of Lenvatinib, Pembrolizumab, and Standard Chemotherapy for Head and Neck Squamous Cell Carcinoma That has Returned or Spread

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Jul 2020 → 30 Oct 2025

Decision date (initial)

2024-04-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Eisai Inc. · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-500820-31-00

EudraCT number

2019-000569-19

WHO UTN

U1111-1278-2707

ClinicalTrials.gov

NCT04428151

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To compare lenvatinib + pembrolizumab combination therapy and SOC chemotherapy with respect to OS

Secondary objectives 4

1. To compare lenvatinib + pembrolizumab combination therapy and SOC chemotherapy with respect to PFS per RECIST 1.1 by BICR.
2. To compare lenvatinib + pembrolizumab combination therapy and SOC chemotherapy with respect to ORR per RECIST 1.1 as assessed by BICR.
3. To assess the efficacy of lenvatinib + pembrolizumab combination therapy and SOC chemotherapy with respect to DOR per RECIST 1.1, by BICR.
4. To assess the safety and tolerability of study intervention with lenvatinib + pembrolizumab combination therapy, SOC chemotherapy, and lenvatinib monotherapy

Conditions and MedDRA coding

Recurrent or metastatic squamous cell carcinoma of the head and neck

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Pathologically confirmed recurrent (not amenable to curative treatment with local and/or systemic therapies) or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies
2. Disease progression at any time during or after treatment with a platinum-containing (e.g., carboplatin or cisplatin) regimen
3. Disease progression on or after treatment with an anti-PD-1/PD-L1 mAb (programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody)
4. Pre-study imaging that demonstrates evidence of disease progression based on investigator review of at least 2 pre-study images per RECIST 1.1, following initiation of treatment with a PD-1/PD-L1 inhibitor
5. Measurable disease by CT or MRI based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as verified by blinded independent central review (BICR). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
6. ECOG performance status of 0 or 1 assessed within 7 days of the first dose of study intervention
7. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 1 week after the last dose of lenvatinib, 3 months after the last dose of capecitabine and paclitaxel, and 6 months after the last dose of docetaxel: refrain from donating sperm; be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermia; contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 1 month post lenvatinib, whichever occurs last (Arms 1 and 3), or during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab (Arm 2); female participants who randomize to Arm 2 must also agree not to donate or freeze/store eggs during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab
9. Adequately controlled blood pressure (BP) with or without antihypertensive medications
10. Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
11. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
12. Adequate organ function

Exclusion criteria 23

1. Disease that is suitable for local therapy administered with curative intent
2. Life expectancy of less than 3 months and/or has rapidly progressing disease in the opinion of the treating investigator
3. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease
4. Active infection requiring systemic therapy
5. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
6. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
7. Known additional malignancy that is progressing or has required active systemic treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ that have undergone potentially curative therapy
8. Active autoimmune disease that has required systemic treatment in the past 2 years
9. Had an allogeneic tissue/solid organ transplant
10. Known history of human immunodeficiency virus (HIV) infection
11. History of any contraindication or has a severe hypersensitivity to any components of pembrolizumab, lenvatinib or SOC chemotherapy.
12. Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
13. History of a gastrointestinal malabsorption or any other condition or procedure that may affect oral study drug absorption
14. Had major surgery within 3 weeks prior to first dose of study interventions
15. Clinically significant cardiovascular impairment within 12 months of the first dose of study drug
16. Active tuberculosis
17. Has difficulty swallowing capsules or ingesting a suspension orally, or by a feeding tube
18. Prior treatment with lenvatinib
19. Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1 or has not recovered from adverse events (AEs) due to a previously administered agent. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible
20. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines is allowed
21. Previously treated with 4 or more systemic regimens given for recurrent/metastatic disease
22. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
23. Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 5

1. Progression-Free Survival (PFS)
2. Objective Response Rate (ORR)
3. Duration of Response (DOR)
4. Number of Participants Who Experienced One or More Adverse Events (AEs)
5. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)

Investigational products

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

Test 3

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Behzad Bidadi, MD, MS

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Behzad Bidadi, MD, MS

Third parties 6

Locations

6 EU/EEA countries · 24 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 72 files

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

Application history

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