Toripalimab plus chemotherapy as first-line treatment for recurrent and/or metastatic nasopharyngeal cancer: safety and activity in non-endemic population

Status Authorised, recruitment pending · 1 EU/EEA countries · 12 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Authorised, recruitment pending

Participants planned 49

Countries 1

Sites 12

Recurrent Metastatic Nasopharingeal Carcinoma

To determine the incidence of high-grade (CTCAE v 5.0 Grade 3 or higher), treatment-related, selected adverse events in patients with RM NPC regardless of EBV status treated with toripalimab plus chemotherapy.

Key facts

Sponsor: Humanitas Mirasole S.p.A.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Decision date (initial): 2025-10-13
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Secondary objectives 3

To determine the incidence and to characterize the outcome (duration of serious adverse events [SAE] treatment, dose of immune-modulating agents [ie, steroids] dose of agents used, time to event onset, and event resolution, and worst grade of event) of all high-grade (CTCAE v 5.0 Grade 3 or higher) adverse events;
To further assess safety and tolerability in all treated subjects;
To evaluate the activity of study treatment in all treatment subjects;

Conditions and MedDRA coding

Recurrent Metastatic Nasopharingeal Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

Subjects must have signed and dated an IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
Males and Females, 18 years of age or older.
Histologically confirmed recurrent or metastatic NPC not amenable to local therapy with curative intent, regardless of Epstein Barr-Virus (EBV) status.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Patients have not received a prior line of systemic therapy for R/M NPC.
Measurable disease by CT or MRI per RECIST 1.1 criteria.
Documentation of EBER-positive or EBER-negative status at diagnosis and EBV DNA plasmatic levels.

Exclusion criteria 7

Allergy to monoclonal antibodies, any toripalimab components, gemcitabine, cisplatin and other platinum drugs.
Patients with untreated, symptomatic CNS metastases.
Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
Prior malignancy within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
Pregnancy or breastfeeding.
Subjects with active, known or suspected autoimmune disease. Subjects with experienced GVH disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or previous neck RT only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Incidence of high-grade (CTCAE v 5.0 grade 3 or higher), treatment related adverse events

Secondary endpoints 5

Incidence of all high-grade (Grades 3-5), selected adverse events, independently from the association with the study drugs;
Median time to onset and median time to resolution (Grades 3-4) of selected adverse events (resolution of an AE is a subject experiencing complete resolution or improvement to the baseline grade for the AE);
Safety and tolerability measured by the incidence of all AEs, treatment-related AEs, serious AEs, deaths, laboratory abnormalities, and select AEs such as pulmonary, gastrointestinal, skin, renal, hepatic, pancreatic, neurologic, endocrine, infusion-related, or hypersensitivity.
Investigator-assessed Progression Free Survival (PFS) defined as radiological evidence of progression, significant clinical symptomatic progression, the need to introduce a non-study drug therapy or death from any cause.
Overall Survival defined as the time from first dosing date to the date of death. A subject who has not died will be censored at last known date alive.

Investigational products

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

Test 15

LOQTORZI 240 mg concentrate for solution for infusion

PRD12532658 · Product

Active substance: Toripalimab
Substance synonyms: TAB-001, JS-001, IMMUNOGLOBULIN G4, ANTI-(HUMAN PROGRAMMED CELL DEATH PROTEIN 1) (HUMAN MONOCLONAL JS001 .GAMMA.4-CHAIN), DISULFIDE WITH HUMAN MONOCLONAL JS001 .KAPPA.-CHAIN, DIMER
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 240 mg milligram(s)
Max total dose: 7680 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF — -
Marketing authorisation: EU/1/24/1853/001
MA holder: TOPALLIANCE BIOSCIENCES EUROPE LIMITED
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatino Accord Healthcare Italia 1 mg/ml concentrato per soluzione per infusione

PRD3327488 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 040210015
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

CISPLATINO Pfizer 50 mg/50 ml soluzione per infusione

PRD411642 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 032775025
MA holder: PFIZER ITALIA S.R.L.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatino Teva Italia 1 mg/ml concentrato per soluzione per infusione

PRD667049 · Product

Active substance: Cisplatin
Pharmaceutical form: INJECTION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 039054046
MA holder: TEVA ITALIA S.R.L.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatino Sandoz

PRD773633 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 033346040
MA holder: SANDOZ S.P.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatino Hikma 1mg/ml concentrato per soluzione per infusione

PRD9651336 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 049681012
MA holder: HIKMA FARMACÊUTICA (PORTUGAL), S.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatino Sandoz

PRD10787621 · Product

Active substance: Cisplatin
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 80 mg/m2 milligram(s)/sq. meter
Max total dose: 480 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: 033346038
MA holder: SANDOZ S.P.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina Accord 100 mg/ml concentrato per soluzione per infusione.

PRD3332925 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 040928044
MA holder: ACCORD HEALTHCARE S.L.U.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina Aurobindo Pharma Italia 40 mg/ml concentrato per soluzione per infusione

PRD10455805 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 044078018
MA holder: EUGIA PHARMA (MALTA) LTD
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Solgekma 38mg/ml concentrato per soluzione per infusione

PRD8814484 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 048916011
MA holder: HIKMA FARMACÊUTICA (PORTUGAL), S.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina Hikma 2g polvere per soluzione per infusione

PRD2049404 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 039727058
MA holder: HIKMA FARMACÊUTICA (PORTUGAL), S.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina Hikma 200 mg polvere per soluzione per infusione

PRD1182160 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 039727019
MA holder: HIKMA FARMACÊUTICA (PORTUGAL), S.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina Hikma 1 g polvere per soluzione per infusione

PRD1182158 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 039727033
MA holder: HIKMA FARMACÊUTICA (PORTUGAL), S.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemcitabina SUN 1 g polvere per soluzione per infusione

PRD985805 · Product

Active substance: Gemcitabine
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 038815027
MA holder: SUN PHARMACEUTICAL INDUSTRIES EUROPE B.V.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Gemsol

PRD773644 · Product

Active substance: Gemcitabine Hydrochloride
Substance synonyms: 4-AMINO-1-[(2R,4R,5R)-3,3-DIFLUORO-4-HYDROXY-5-(HYDROXYMETHYL)OXOLAN-2-YL]PYRIMIDIN-2-ONE HYDROCHLORIDE
Pharmaceutical form: CONCENTRATE FOR SOLUTION FOR INFUSION
Route of administration: IV INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: L01BC05 — GEMCITABINE
Marketing authorisation: 040278044
MA holder: SANDOZ S.P.A.
MA country: Italy
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Humanitas Mirasole S.p.A.

Sponsor organisation: Humanitas Mirasole S.p.A.
Address: Via Alessandro Manzoni 56
City: Rozzano
Postcode: 20089
Country: Italy

Scientific contact point

Organisation: Humanitas Mirasole S.p.A.
Contact name: Paolo Bossi

Public contact point

Organisation: Humanitas Mirasole S.p.A.
Contact name: Paolo Bossi

Third parties 1

Organisation	City, country	Duties
Clinical Research Technology S.r.l. ORG-100027504	Salerno, Italy	On site monitoring, Code 12, Code 5, Data management, E-data capture, Code 8

Locations

1 EU/EEA country · 12 investigational sites

By country

Country	MS status	Planned subjects	Sites
Italy	Authorised, recruitment pending	49	12
Rest of world	—	0	—

Investigational sites

Italy

12 sites · Authorised, recruitment pending

Fondazione IRCCS Istituto Nazionale Dei Tumori

S.C Oncologia Medica 3 Tumori della Testa e del Collo, Via Giacomo Venezian 1, 20133, Milan

Fondazione IRCCS Policlinico San Matteo

Oncologia, Viale Camillo Golgi 19, 27100, Pavia

IRCCS Ospedale Policlinico San Martino

Oncologia medica 2, Largo Rosanna Benzi 10, 16132, Genoa

Istituto Oncologico Veneto

Oncologia medica 2, Via Gattamelata 64, 35128, Padova

Azienda Ospedaliero Universitaria Careggi

Radioterapia oncologica, Largo Giovanni Alessandro Brambilla 3, 50134, Florence

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

UO Oncologia Medica, Via Del Vespro 129, 90127, Palermo

Istituto Europeo Di Oncologia S.r.l.

Oncologia Medica Urogenitale e Cervico Facciale, Via Giuseppe Ripamonti 435, 20141, Milan

I.F.O. Istituti Fisioterapici Ospitalieri

Oncologia Medica 1, Via Elio Chianesi N 53, 00144, Rome

Azienda Ospedaliero-Universitaria Policlinico Umberto I

U.O. Oncologia Cervico Facciale, Viale Del Policlinico 155, 00161, Rome

Humanitas Mirasole S.p.A.

Oncologia Medica, Via Alessandro Manzoni 56, 20089, Rozzano

IRCCS Istituto Nazionale Tumori Fondazione Pascale

UO Oncologia Medica Testa-Collo, Via Mariano Semmola 52, 80131, Naples

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

UOC Oncologia medica, Largo Francesco Vito 1, 00168, Rome

Results and documents

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

Documents 16 files

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

Type	Title	Version
Protocol (for publication)	D_THOR - Protocol_v3_0_30Sep2025_FP	3.0
Protocol (for publication)	THOR - Protocol_v3_30Sep2025_TC	3.0
Recruitment arrangements (for publication)	K1_THOR_Recruitment arrangements - Italy_v1_0_6june25	1
Subject information and informed consent form (for publication)	L_THOR_ICF_v1_0_9JUN2025	1
Subject information and informed consent form (for publication)	L1_THOR_ICF_v2_0_15Sep2025_Clean	2.0
Subject information and informed consent form (for publication)	L1_THOR_ICF_v2_0_15Sep2025_TC	2.0
Summary of Product Characteristics (SmPC) (for publication)	E_Gemcitabina_RCP_conc	NA
Summary of Product Characteristics (SmPC) (for publication)	E_Gemcitabina_RCP_pol	NA
Summary of Product Characteristics (SmPC) (for publication)	Loqtorzi (toripalimab) SmPC	NA
Summary of Product Characteristics (SmPC) (for publication)	RCP_CISPLATINO	Na
Summary of Product Characteristics (SmPC) (for publication)	THOR-SmPC_Cisplatin	NA
Summary of Product Characteristics (SmPC) (for publication)	THOR-SmPC_Gemcitabine_conc	NA
Summary of Product Characteristics (SmPC) (for publication)	THOR-SmPC_Gemcitabine_powder	NA
Synopsis of the protocol (for publication)	D_THOR - Protocol Synopsis_ENG	2.0
Synopsis of the protocol (for publication)	D_THOR - Sinossi in ITA v3_0_30Sep2025	3.0
Synopsis of the protocol (for publication)	THOR - Sinossi in ITA v3_30Sep2025_TC	3.0

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2025-07-02	Italy	Acceptable 2025-10-06	2025-10-13
2	SUBSTANTIAL MODIFICATION	SM-1	2025-11-14	Italy	Acceptable	2026-01-08
3	SUBSTANTIAL MODIFICATION	SM-3	2026-02-23	Italy	Acceptable 2026-04-27	2026-04-28

Toripalimab plus chemotherapy as first-line treatment for recurrent and/or metastatic nasopharyngeal cancer: safety and activity in non-endemic population

Overview

Key facts

Trial design

Main objective

Secondary objectives 3

Conditions and MedDRA coding

Eligibility criteria

Inclusion criteria 8

Exclusion criteria 7

Endpoints

Primary endpoints 1

Secondary endpoints 5

Investigational products

Test 15

Sponsors and contacts

Humanitas Mirasole S.p.A.

Scientific contact point

Public contact point

Third parties 1

Locations

By country

Investigational sites

Results and documents

Documents 16 files

Application history

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