A Phase II, Open-Label, Single-Arm, Multicentre Study of Carboplatin, Paclitaxel, and Tislelizumab in Biomarker-Selected Patients with Resectable Locally Advanced Oral Cavity Squamous Cell Carcinoma - PERSEPHONE Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione GONO Plus

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-09-15

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: Therapy, Efficacy, Safety

To evaluate the anti-tumor activity of the study combination in locally advanced oral cavity squamous cell carcinoma.

Secondary objectives 5

1. To evaluate the safety of study combination in locally advanced oral cavity squamous cell carcinoma
2. To evaluate the survival outcome of the subjects under the study treatment in terms of disease free survival (DFS) and overall survival (OS).
3. Exploratory objectives: to evaluate longitudinal modification in circulating-DNA (ctDNA) and immune infiltrates in tumor samples and to correlate them with pathological response after neoadjuvant therapy;
4. Exploratory objectives: to identify biomarkers for neoadjuvant treatments response on multiplexed imaging mass cytometry (IMC);
5. Exploratory objectives: To evaluate survival and longitudinal ctDNA of patients who meet clinical eligibility criteria with the exception of the bio-molecular inclusion criteria.

Conditions and MedDRA coding

Resectable Locally Advanced Oral Cavity Squamous Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Patients of both genders, aged ≥18 years
2. Willing and able to sign written informed consent prior to study screening
3. Histologically confirmed, squamous cell carcinoma of the oral cavity
4. Disease amenable for local surgery with curative intent
5. Stage III-IV(M0) according to the VIII edition of AJCC staging system
6. Biomolecular inclusion criteria: CPS PDL-1 > 1 tumours and CD8+/FOXP3+ ratio equal or higher than 4. PD-L1 status will be assessed by VENTANA PD-L1 assay and/or 22C3pharmDX. In tumour biopsies performed multiplex-immunofluorescence (mIF) will analyse CD8+/FOXP3+ ratio. The analysis will be carried out by a central laboratory
7. Performance status ECOG 0-1
8. Availability of tumour tissue via biopsy and provided for study purposes. Needle or resected tissue is required; cytological specimens such as fine needle aspirated or cell block are not acceptable
9. Willing to provide blood samples for study purposes
10. Patient has adequate organ and marrow function (absolute neutrophil count ≥ 1500, haemoglobin ≥ 9.0 gram/decilitre (g/dL), platelet count ≥ 100,000, total bilirubin ≤1.5 times institution's upper limit of normal, AST/SGOT and ALT/SPGT ≤ 2.5 times institutional upper limit of normal, albumin ≥ 2.0 g/dL, serum creatinine ≤ 1.5 times institutional upper limit of normal or creatinine clearance ≥ 60 millilitres per minute (mL/min) according to Cockroft-Gault formula, or local institutional standard method)
11. Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment
12. Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must have a negative serum pregnancy test at screening and must not be breastfeeding.
13. Women of childbearing potential must agree to use highly effective contraceptive method(s) from ICF signature to 6 months after the last dose of study treatment, whichever is the latest. See Section 5.4 for a list of acceptable birth control methods.
14. Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use condom and spermicide from ICF signature to 6 months after the last dose of study treatment, whichever is the latest. Because male condom and spermicide is not a highly effective contraception method, it is required that female partners of a male study subject use highly effective contraceptive method(s) throughout this period.
15. Male subjects must refrain from donating sperm during the clinical study and for 6 months after the last dose of study treatment, whichever is the latest. If not done previously, cryopreservation of sperm prior to receiving chemotherapy + tislelizumab is advised to male patients with a desire to have children.
16. Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.

Exclusion criteria 23

1. Patient has recurrent/metastatic disease
2. Patient with locally advanced disease not amenable of surgery with curative intent
3. Patient has received prior local or systemic treatment for HNSCC
4. Patient must not be simultaneously enrolled in an interventional clinical trial
5. Patient must not have had major surgery ≤3 weeks prior to initiating protocol therapy and patient must have recovered from any surgical effects
6. Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior initiating protocol therapy
7. Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy
8. Participant must not have a known allergy to tislelizumab, paclitaxel or carboplatin components or excipients
9. Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy
10. Participant must not have a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, hypertension (defined as systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg) that has not been adequately controlled or treated; prior history of posterior reversible encephalopathy syndrome, or any psychiatric disorder that prohibits obtaining informed consent
11. Participant must not have known, symptomatic brain or leptomeningeal metastases
12. Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
13. Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
14. Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
15. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol
16. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrolment. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
17. Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
18. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
19. Known active Hepatitis B infection (defined as presence of HBsAg and/or HBV DNA), active hepatitis C infection (defined as positive HCV RNA), unless it is under stable treatment and/or with undetectable viral load and/or known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4 count (≥ 200) and an undetectable viral load are not excluded
20. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 72 hours before treatment start. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 6 months after the last dose of study treatment
21. Known medical condition that, in the investigator’s opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
22. History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial
23. Participant has received a live vaccine within 14 days of initiating protocol therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Activity: rate of Major Pathological Response (MPR, i.e. less than 10% viable tumour cells identified on routine haematoxylin and eosin staining in pathological surgical specimen) in patients with locally advanced oral cavity squamous cell carcinoma treated with tislelizumab + carboplatin + paclitaxel in the neoadjuvant setting.

Secondary endpoints 5

1. Safety: Number of adverse events and percentages, stratified for grade, of the neoadjuvant treatment with tislelizumab + carboplatin + paclitaxel measured by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
2. Survival a) 3-year overall survival (OS); b) 3-year disease free survival (DFS), defined as the time from treatment assignment to cancer recurrence, second cancer or death from any cause.
3. Exploratory endpoint: To evaluate longitudinal modification in circulating-DNA (ctDNA) and immune infiltrates in tumour samples and to correlate them with pathological response after neoadjuvant therapy;
4. Exploratory endpoint: Identification, quantification and correlation of specific biomarkers (e.g., protein expression patterns, immune cell phenotypes) associated with treatment response, measured via IMC in pre-treatment and post-treatment tissue samples
5. Exploratory endpoint: Overall survival (OS), progression-free survival (PFS) and longitudinal ctDNA levels evaluated in the subgroup of patients who lack bio-molecular eligibility but meet other clinical criteria.

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione GONO Plus

Sponsor organisation

Fondazione GONO Plus

Address

Interno 11, Via Cesarea 8 Via Cesarea 8

City

Genoa

Postcode

16121

Country

Italy

Scientific contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Paolo Bossi

Public contact point

Organisation

Gruppo Oncologico Del Nord Ovest

Contact name

Paolo Bossi

Third parties 1

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

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

Documents 10 files

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

Application history

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