A phase 3 study to evaluate petosemtamab vs. investigator's choice in previously treated metastatic / recurrent head and neck cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merus N.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jan 2025 → ongoing

Decision date (initial)

2024-09-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merus N.V.

External identifiers

EU CT number

2023-510322-32-00

WHO UTN

U1111-1304-0642

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To compare overall survival (OS) in participants with incurable metastatic / recurrent HNSCC who progressed on or after anti-programmed cell death protein 1 (PD-1) and platinum containing therapy, treated with petosemtamab monotherapy vs Investigator’s choice monotherapy

Secondary objectives 9

1. 2. To evaluate antitumor activity measured by progression-free survival (PFS) per RECIST v1.1, as assessed by BICR
2. 3. To evaluate antitumor activity as measured by duration of response (DOR) per RECIST v1.1, as assessed by BICR
3. 4. To evaluate antitumor activity in ORR per RECIST v1.1 as assessed by Investigator review
4. 5. To evaluate antitumor activity in PFS per RECIST v1.1 as assessed by Investigator review
5. 6. To evaluate antitumor activity in DOR per RECIST v1.1 as assessed by Investigator review
6. 7. To evaluate antitumor activity in time to response (TTR) per RECIST v1.1 as assessed by BICR and Investigator review
7. 8. To evaluate antitumor activity in clinical benefit rate (CBR) per RECIST v1.1 as assessed by BICR and by Investigator review
8. 9. To evaluate safety and tolerability of petosemtamab monotherapy
9. 1. To evaluate antitumor activity in objective response rate (ORR) per RECIST v1.1 as assessed by blinded independent central review (BICR)

Conditions and MedDRA coding

patients with incurable, metastatic/recurrent 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 14

1. 1. Willing and able to provide signed ICF before initiation of any study procedures. Participants unable to provide their own consent will not be eligible to participate in the study.
2. 10. ECOG PS of 0 or 1
3. 11. Life expectancy ≥ 12 weeks, as per investigator
4. 2. Age ≥ 18 years at signing of ICF
5. 3. Histologically previously confirmed HNSCC with evidence of metastatic or locally advanced disease not amenable to standard therapy with curative intent.
6. 4. HNSCC participants progressed on or after anti-PD-1 therapy and platinum-containing therapy.
7. 5. The eligible HNSCC primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
8. 6. Documentation of p16 status (positive or negative) by local laboratory IHC for participants with primary oropharyngeal cancer must be available before further clinical assessment to determine eligibility.
9. 7. Previous treatments with anti-EGFR therapies are not allowed, unless cetuximab was used with radiotherapy as a multimodal treatment of local disease and the recurrence/progression of the disease was ≥1 year from the last dose of cetuximab
10. 8. The participant is amenable for a new tumor biopsy or providing archival tumor tissue.
11. 9. Measurable disease per Investigator assessment as defined by RECIST v1.1 by radiologic methods
12. 12. Adequate organ function (as per protocol)
13. 13. Human immunodeficiency virus (HIV)-positive participants.
14. 14. Judged appropriate by the Investigator to receive Investigator’s choice monotherapy, if randomized to that treatment arm.

Exclusion criteria 14

1. 1. Metastasen in het centraal zenuwstelsel die onbehandeld of symptomatisch zijn, of bestraling, een operatie of voortzetting van steroïdentherapie nodig hebben om de symptomen onder controle te houden binnen 14 dagen vóór randomisatie
2. 2. Known leptomeningeal involvement
3. 3. Enrolled in any clinical study with petosemtamab, regardless if petosemtamab was received or not
4. 4. Any systemic anticancer therapy investigational drug (including those with indications other than anticancer therapy), or live or live attenuated vaccine within 4 weeks or 5 half-lives (if known), whichever is shorter, prior to randomization
5. 5. Major surgery within 3 weeks prior to randomization or palliative radiotherapy within 2 weeks prior to randomization
6. 6. Clinically significant toxicities related to prior antineoplastic therapies that have not returned to ≤ Grade 1 or baseline except for alopecia, and ≤ Grade 2 prior therapy-related endocrinopathies
7. 7. History of hypersensitivity reaction to any of the excipients of treatment required for this study.
8. 8. Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment or history of myocardial infarction within 6 months prior to randomization
9. 9. History of prior malignancies within the last 5 years except for localized cancer with curative resection (e.g., cervical intraepithelial neoplasia, non-melanoma skin cancers)
10. 10. Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen therapy. History of non-infectious pneumonitis/instestitial lung disease or evidence of current interstitial lung disease on baseline scan
11. 11. Current serious illness or medical conditions including, but not limited to, uncontrolled active infection, clinically significant pulmonary, metabolic or psychiatric disorders
12. 12. Participants with known infectious diseases (as per protocol)
13. 13. Pregnant or breastfeeding participants
14. 14. Participant has a primary tumor site of nasopharynx, or sinonasal (any histology).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS)

Secondary endpoints 12

1. 2. Progression Free Survival PFS per RECIST v1.1 as assessed by BICR
2. 3. DOR per RECIST v1.1 as assessed by BICR
3. 4. ORR per RECIST v1.1 as assessed by investigator review
4. 5. PFS per RECIST v1.1 as assessed by investigator review
5. 6. DOR per RECIST v1.1 as assessed by investigator review
6. 7. TTR per RECIST v1.1 as assessed by BICR and by Investigator review
7. 8. CBR per RECIST v1.1 as assessed by BICR and by Investigator review
8. 9. Proportion of participants experiencing TEAEs
9. 10. Proportion of participants experiencing serious TEAEs
10. 11. Proportion of participants who discontinued study treatment due to TEAEs
11. 12. Proportion of participants who had dose reductions due to TEAEs
12. 1. Objective response rate (ORR) per RECIST v1.1 as assessed by BICR.

Investigational products

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

Test 1

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merus N.V.

Sponsor organisation

Merus N.V.

Address

Floor 3rd And 4th, Uppsalalaan 17 Uppsalalaan 17

City

Utrecht

Postcode

3584 CT

Country

Netherlands

Scientific contact point

Organisation

Merus N.V.

Contact name

Clinical Trial Information

Public contact point

Organisation

Merus N.V.

Contact name

Clinical Trial Information

Third parties 10

Locations

12 EU/EEA countries · 81 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

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 145 files

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

Application history

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