Phase 2, open-label, multicentre, single-arm study to evaluate the activity of the combination of EGFR inhibitors and c-MET inhibitors in patients with platinum-resistant head and neck squamous cell carcinoma after relapse to immunotherapy.

2024-518892-72-00 Protocol TEPMEETCET Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 11 sites · Protocol TEPMEETCET

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 30
Countries 1
Sites 11

Head and neck cancer

To evaluate the activity of tepotinib in combination with cetuximab in terms of tumor response

Key facts

Sponsor
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia, Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Neoplasms [C04]
Decision date (initial)
2025-01-31
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes

External identifiers

EU CT number
2024-518892-72-00
EudraCT number
2022-002841-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the activity of tepotinib in combination with cetuximab in terms of tumor response

Conditions and MedDRA coding

Head and neck cancer

VersionLevelCodeTermSystem organ class
21.1 PT 10067821 Head and neck cancer 100000004864

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Adults >= 18 years old
  2. Histologically confirmed HNSCC from any primary site; nasopharyngeal carcinoma and paranasal sinus, will be included; squamous cell carcinoma of unknown primary, clearly related to the head and neck, will be included
  3. Recurrent/metastatic disease, fulfilling at least one of the criteria defined below: a) Incurable disease as assessed by surgical or radiation oncology b) Metastatic (M1) disease c) Persistent or progressive disease following curative-intent radiation, and not a candidate for surgical salvage due to incurability or morbidity; patients who decline radical surgery are eligible
  4. For patients with oropharyngeal primary site or unknown primary site only: tumoral human papillomavirus (HPV) status must be negative, as established; acceptable standards include p16 immunohistochemistry (where a tumor is classified as p16-positive when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or assessment of HPV deoxyribonucleic acid (DNA) For patients with nasopharyngeal cancer only or unknown primary site only: tumoral Epstein- Barr Virus (EBV) status must be negative.

Exclusion criteria 7

  1. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agen
  2. Prior treatment with a hepatocyte growth factor (HGF)/cMet inhibitor such as rilotumumab, crizotinib, MetMAb, or ARQ197
  3. Uncontrolled central nervous system (CNS) metastases, including leptomeningeal metastases, are not allowed; subjects with previously treated brain metastases will be allowed if the brain metastases have been stable without steroid treatment for at least 2 weeks (radiotherapy or surgery)
  4. Failure to recover to grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above; a washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required
  5. Previous treatment with cetuximab for RM disease. Use of cetuximab is allowed if given concurrently with radiation
  6. Significant pulmonary disease, including pulmonary hypertension or interstitial pneumonitis
  7. Peripheral edema >= grade 2 per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Objective response (OR, confirmed complete response [CR] or partial response [PR]) determined according to RECIST Version 1.1 assessed by the Investigators

Investigational products

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

Test 2

Cetuximab

SUB01178MIG · Substance

Active substance
Cetuximab
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INFUSION
Max daily dose
400 mg/m2 milligram(s)/sq. meter
Max total dose
5 mg/ml milligram(s)/millilitre
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Tepotinib

SUB189535 · Substance

Active substance
Tepotinib
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
225 mg milligram(s)
Max total dose
225 Other
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Primary packaging

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

8 Total trials 2 Recruiting
Academic / Non-commercial
Sponsor organisation
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Address
Piazzale Spedali Civili 1
City
Brescia
Postcode
25123
Country
Italy

Scientific contact point

Organisation
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Contact name
Clinical Trial Center, CREA Laboratory Unit

Public contact point

Organisation
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Contact name
Clinical Trial Center, CREA Laboratory Unit

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

8 Total trials 2 Recruiting
Academic / Non-commercial
Sponsor organisation
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Address
Piazzale Spedali Civili 1
City
Brescia
Postcode
25123
Country
Italy

Sponsor responsibilities

Article 77 compliance
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Contact point sponsor
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Article 77 implementation
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Locations

1 EU/EEA country · 11 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 30 11
Rest of world — 0 —

Investigational sites

Italy

11 sites · Authorised, recruitment pending
Istituto Oncologico Veneto
Oncology, Via Gattamelata 64, 35128, Padova
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Oncology, Piazzale Spedali Civili 1, 25123, Brescia
Istituto Nazionale dei Tumori
Oncology, Via Giacomo Venezian 1, 20133, Milano
Azienda Ospedaliero Universitaria Careggi
Oncology, Largo Giovanni Alessandro Brambilla 3, 50134, Florence
Istituto Europeo Di Oncologia S.r.l.
Oncology, Via Giuseppe Ripamonti 435, 20141, Milan
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Oncology, Viale Del Policlinico 155, 00161, Rome
Ospedale Bellaria - Azienda USL di Bologna
Oncology, Via Altura 3, 40139, Bologna
IRCCS Ospedale Policlinico San Martino
Oncology, Largo Rosanna Benzi 10, 16132, Genoa
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Oncology, Largo Francesco Vito 1, 00168, Rome
Istituti Clinici Scientifici Maugeri S.p.A. Societa' Benefit In Forma Abbreviata Istituti Clinici Scientifici Maugeri S.p.A. Sb O Anche Ics Maugeri S.p.A. Sb O Maugeri S.p.A. Sb
Oncology, Via Salvatore Maugeri 4, 27100, Pavia
Humanitas Mirasole S.p.A.
Onoclogy, Via Francesco Nava 31, 20159, Milan

Results and documents

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

Documents 14 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_SM01_2024-518892-72-00_Clean_Redacted 2
Recruitment arrangements (for publication) INTENTIONALLY LEFT BLANK - PER TRANSIZIONI 1
Subject information and informed consent form (for publication) L1_SIS and ICF pregnancy_SM01_2024-518892-72-00_Clean 2
Subject information and informed consent form (for publication) L1_SIS and ICF translational study_SM01_2024-518892-72-00_Clean 2
Subject information and informed consent form (for publication) L1_SIS and ICF_SM01_2024-518892-72-00 2
Subject information and informed consent form (for publication) L2_Letter to General Practitioner_SM01_2024-518892-72-00_Clean 2
Subject information and informed consent form (for publication) L2_Privacy Information Sheet and ICF ASST BS_SM01_2024-518892-72-00 28072025 2
Subject information and informed consent form (for publication) L2_Privacy Information Sheet and ICF MASTER_SM01_2024-518892-72-00 28072025 2
Subject information and informed consent form (for publication) Questionari v 1 del 5Aug2022 2 1
Subject information and informed consent form (for publication) Questionari v 1del 5Aug2022 1 1
Summary of Product Characteristics (SmPC) (for publication) E2_SmPC Tepmetko 1
Summary of Product Characteristics (SmPC) (for publication) RCP_Erbitux_data di revisione 052022 1
Summary of Product Characteristics (SmPC) (for publication) tepmetko-epar-product-information_it 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_IT_SM01_2024-518892-72-00_Clean_Redacted 2

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-11-29 Italy Acceptable
2025-01-09
 2025-01-31
2 SUBSTANTIAL MODIFICATION SM-1 2025-09-15 Italy Acceptable
2025-11-28
 2025-12-01

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