A phase 3 study to evaluate petosemtamab plus pembrolizumab vs pembrolizumab in first-line treatment of head and neck cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merus B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Jan 2025 → ongoing

Decision date (initial)

2026-02-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merus N.V.

External identifiers

EU CT number

2023-510323-30-00

WHO UTN

U1111-1304-0807

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Pharmacokinetic, Safety, Therapy

To compare OS in the 1L setting of incurable metastatic/recurrent HNSCC participants eligible for pembrolizumab monotherapy with tumors expressing PDL1 treated with petosemtamab in combination with pembrolizumab vs. pembrolizumab alone.

To compare ORR per Response Evaluation Criteria in Solid Tumor (RECIST) Guidelines version (v) 1.1 in the 1L setting of incurable metastatic/recurrent HNSCC participants eligible for pembrolizumab monotherapy with tumors expressing PDL1 (CPS≥1) without previous anti PD-(L)1 and EGFR therapies, treated with petosemtamab in combination with pembrolizumab vs. pembrolizumab alone.

Secondary objectives 4

1. 1. To evaluate antitumor activity in PFS per RECIST v1.1
2. 2. To evaluate antitumor activity in DOR per RECIST v1.1
3. 3. To evaluate antitumor activity in clinical benefit rate (CBR) per RECIST v1.1
4. 4. To evaluate antitumor activity as measured by percentage of participants with PFS at visit 1 and visit 2 per RECIST v1.1, as assessed by BICR

Conditions and MedDRA coding

First-line treatment of recurrent or metastatic PD-L1+ head and neck squamous cell carcinoma.

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. 1. Signed ICF before initiation of any study specific procedures
2. 2. Age ≥ 18 years at signing of ICF
3. 3. Histologically confirmed HNSCC with evidence of metastatic or locally recurrent disease not amenable to local therapy with curative intent. Participants with HNSCC primary tumor locations in oropharynx, oral cavity, hypopharynx, and larynx are eligible.
4. 4. HNSCC participants eligible to receive pembrolizumab as 1L monotherapy with tumors expressing PD L1, CPS ≥1, as determined by an IHC test in a central laboratory
5. 5. HNSCC participants should not have had previous systemic therapy administered in the incurable recurrent or metastatic setting, although previous systemic therapy as part of multimodal treatment for locally advanced disease is allowed if progressive disease (PD) was ≥6 months after the last platinum-containing therapy dose. Previous treatments with anti PD-(L)1 or anti-EGFR therapies are not allowed.
6. 6. Tumor tissue biopsy (as specified per protocol)
7. 7. Measurable disease as defined by RECIST v1.1 by radiologic methods
8. 8. ECOG PS of 0 or 1
9. 9. Life expectancy ≥ 12 weeks, as per investigator assessment
10. 10. Left ventricular ejection fraction (LVEF) ≥50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan
11. 11. Adequate organ function (as per protocol)
12. 12. Human immunodeficiency virus (HIV) positive participants are eligible (if certain criteria are met per protocol).

Exclusion criteria 18

1. 1. Central nervous system (CNS) metastases that are untreated or already treated but symptomatic, or require radiation, surgery, or continued steroid therapy to control symptoms within 21 days of study entry
2. 10. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy. Participants with a history of non-infectious pneumonitis/interstitial lung disease (ILD) or evidence of current pneumonitis/ILD on baseline chest imaging will be excluded.
3. 11. Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic, or psychiatric disorders that preclude safety and efficacy evaluation
4. 12. Participants with known infectious diseases (as per protocol)
5. 13. Pregnant or breastfeeding participants; participants of childbearing potential must use highly effective contraception methods per local standards prior to study entry, for the duration of study participation, and for 6 months after the last dose of petosemtamab or 4 months after the last dose of pembrolizumab, whichever is longer.
6. 14. The participant has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy of prednisone >10 mg/day or equivalent, or any other form of immunosuppressive therapy. Corticosteroids used as premedication for IRRs before Cycle 1 Day 1 as specified in the protocol are allowed.
7. 15. The participant has an active autoimmune disease that has required systemic immune suppressive treatment in the past 2 years; replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered immune suppressive treatment.
8. 16. The participant has had an allogeneic tissue/solid organ transplant
9. 17. Participant has a primary tumor site (as specified per protocol).
10. 2. Known leptomeningeal involvement
11. 3. Any systemic anticancer therapy within 4 weeks of the first dose of study treatment
12. 4. Requirement for immunosuppressive medication (eg, methotrexate, cyclophosphamide)
13. 5. Major surgery or radiotherapy within 3 weeks of the first dose of study treatment
14. 6. Clinically significant toxicities related to prior anticancer therapy that have not returned to ≤ Grade 1 or baseline except for ≤Grade 2 myalgia, neuropathy, alopecia, and prior therapy-related endocrinopathies.
15. 7. History of hypersensitivity reaction to any of the excipients of petosemtamab or pembrolizumab required for this study
16. 8. Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment (except appropriately treated atrial fibrillation, paroxysmal supraventricular tachycardia); or history of myocardial infarction within 6 months of study entry
17. 9. History of prior malignancies, with the exception of excised local cancer, or treated cancer deemed at low risk for recurrence with no evidence of disease for ≥3 years
18. 18. Received a live or live-attenuated vaccine within 28 days prior to randomization

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1. Objective response rate (ORR)
2. 2. Overall survival (OS)

Secondary endpoints 4

1. 1. PFS per RECIST v1.1 as assessed by investigator review
2. 2. The Duration of Response (DoR) per RECIST v1.1 and by investigator review
3. 3. The Clinical Benefit Rate (CBR) per RECIST v1.1 and by investigator review
4. 4. Percentage of participants with PFS at visit 1 and visit 2 per RECIST v1.1 as assessed by BICR

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merus B.V.

Sponsor organisation

Merus B.V.

Address

Floor 3rd And 4th, Uppsalalaan 17 Uppsalalaan 17

City

Utrecht

Postcode

3584 CT

Country

Netherlands

Scientific contact point

Organisation

Merus B.V.

Contact name

Clinical Trial Information

Public contact point

Organisation

Merus B.V.

Contact name

Clinical Trial Information

Third parties 12

Locations

14 EU/EEA countries · 86 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

Documents 153 files

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

Application history

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