PTT-4256 for Solid tumours | Renal cell carcinoma (clear cell) | Papillary renal cell carcinoma | Head and neck squamous cell carcinoma

Inclusion criteria

• {"criterion_text":"- 1.\t≥ 18 years of age at the time of consent."}
• {"criterion_text":"- 2.\tAdditional Module B1 Specific Inclusion Criteria - A formalin fixed, paraffin-embedded (FFPE) tumour tissue block or unstained slides of tumour sample (archival or recent) must be available. Sample should be from a tumour biopsy (eg, excisional, incisional, core needle), as cytological samples (eg, fine needle aspiration) are insufficient."}
• {"criterion_text":"- 3.\tAdditional Module B1 Specific Inclusion Criteria - Participant requires systemic treatment for their cancer, and either a. be refractory to, b. have progressed on, c. be intolerant to, or d. be not otherwise a candidate, in the opinion of the Investigator, for any of the currently available standard treatments including, at least, a PD-1/PD-L1 inhibitor and VEGF TKI."}
• {"criterion_text":"- 1.\tAdditional Module B2 Specific Inclusion Criteria - Participant has histologically confirmed diagnosis of unresectable locally advanced or metastatic ccRCC."}
• {"criterion_text":"- 2. Additional Module B2 Specific Inclusion Criteria - A FFPE tumour tissue block or unstained slides of tumour sample (archival or recent) must be available. Sample should be from a tumour biopsy (eg, excisional, incisional, core needle), as cytological samples (eg, fine needle aspiration) are insufficient."}
• {"criterion_text":"- 3. Additional Module B2 Specific Inclusion Criteria -Participant requires systemic treatment for their cancer, and either be refractory to or have progressed on both a VEGF and a PD-1/PD-L1 inhibitor therapy (administered as combination therapy or as a part of separate prior lines of treatment) if not otherwise contraindicated. Radiologically confirmed disease progression must be demonstrated for the most recently administered regimen, prior to study participation."}
• {"criterion_text":"- 4. Additional Module B2 Specific Inclusion Criteria - Participants should not have an intolerable toxicity to prior anti-PD-1/PD-L1 therapy and, in the opinion of the Investigator, are suitable to receive further checkpoint blockade with nivolumab."}
• {"criterion_text":"- 5.\tAdditional Module B2 Specific Inclusion Criteria - Participants must be eligible to receive nivolumab at the approved dose and schedule according to the current Summary of Product Characteristics (SmPC) (eg, OPDIVO®)."}
• {"criterion_text":"- 1.\tAdditional Module B3 Specific Inclusion Criteria - Participant has histologically confirmed diagnosis of unresectable locally advanced or recurrent or metastatic HNSCC of oral cavity, pharynx, larynx which is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies (eg, mucosal melanoma) are not allowed."}
• {"criterion_text":"- 2.\tAdditional Module B3 Specific Inclusion Criteria - Participant requires systemic treatment for their cancer, and must have progressed on standard-of-care systemic therapy, including both a PD-1/PD-L1 inhibitor (monotherapy or combination) and a chemotherapy regimen; such progression may have occurred in the metastatic / recurrent setting or within 6 months following peri-operative treatment."}
• {"criterion_text":"- 3.\tAdditional Module B3 Specific Inclusion Criteria - A FFPE tumour tissue block or unstained slides of tumour sample (archival or recent) must be available. Sample should be from a tumour biopsy (eg, excisional, incisional, core needle), as cytological samples (eg, fine needle aspiration) are insufficient."}
• {"criterion_text":"- 2.\tParticipant has given written informed consent to participate in the study and is able and willing to adhere to the study protocol."}
• {"criterion_text":"- 4.\tAdditional Module B3 Specific Inclusion Criteria - Documentation of p16-positive or p16-negative disease to determine human papillomavirus (HPV) status of tumour for SCC of the oropharynx."}
• {"criterion_text":"- 5.\tAdditional Module B3 Specific Inclusion Criteria - Participants should have not an intolerable toxicity to prior anti-PD-1/PD-L1 therapy and, in the opinion of the Investigator, are suitable to receive further checkpoint blockade using Nivolumab."}
• {"criterion_text":"- 6.\tAdditional Module B3 Specific Inclusion Criteria - Participants must be eligible to receive nivolumab at the approved dose and schedule according to the current SmPC (eg, OPDIVO®)."}
• {"criterion_text":"- 3.\tParticipant has measurable disease per RECIST v1.1."}
• {"criterion_text":"- 4.\tParticipant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1."}
• {"criterion_text":"- 5.\tParticipant has an estimated life expectancy of at least 3 months in the opinion of the Investigator."}
• {"criterion_text":"- 6.\tAdequate haematological (blood or platelet transfusion not allowed within 7 days prior to Screening), liver, and renal function defined below (repeat measurement of borderline values permitted): •\tHaemoglobin ≥ 8.5 g/dL, •\tAbsolute neutrophil count (ANC) ≥ 1.5 × 109/L, •\tPlatelet count ≥ 90 x 109/L, •\tTotal bilirubin ≤ 1.5 institutional upper limit of normal (ULN), (or where ≤ 2 × ULN with known hepatobiliary metastases or Gilbert’s syndrome), •\tAspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present), •\tEstimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 (calculated using Cockcroft-Gault)."}
• {"criterion_text":"- 7.\tFemales: a.\tmust not be pregnant or lactating, and b.\tmust use acceptable, highly effective contraception from Screening until: \t90 days after last IMP administration (Module A and Module B1) or \t5 months after last IMP administration (Module B2 and Module B3). Effective forms of contraception are defined in Section 7.3.2. c.\tfemales with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle, and d.\twomen of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Day 1 and be willing to have additional pregnancy tests as required throughout the study. WOCBP must not donate ova from signing informed consent until: -\tat least 90 days after the last IMP administration (Module A and Module B1) or -\tat least 5 months after the last IMP administration (Module B2 and B3). WOCBP are defined in Section 7.3.2, or e.\twomen of non-childbearing potential (WONCBP) must be surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal (no menses for ≥ 12 months; or ≥ 60 years of age at the time of consent (postmenopausal status is to be confirmed through testing of follicle-stimulating hormone [FSH] levels ≥ 40 IU/L [except for participants on hormone replacement therapy] at Screening for amenorrhoeic female participants)."}
• {"criterion_text":"- 8.\tMales: a.\tmust be surgically sterile (> 6 months since vasectomy with confirmation of no viable sperm), or b.\tmales with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle, or c.\tif engaged in sexual relations (intercourse) with a WOCBP, either his partner must be surgically sterile (eg, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or a barrier contraceptive method (condom) plus a highly effective contraceptive method (see Section 7.3.2) must be used from Screening until at least 90 days after the last IMP administration, and d.\tMales must not donate sperm from the first dose of IMP until at least 90 days after the last dose of IMP administration."}
• {"criterion_text":"- 1.\tAdditional Module B1 Specific Inclusion Criteria - Participant has histologically confirmed diagnosis of unresectable locally advanced or metastatic RCC including ccRCC or pRCC."}

Exclusion criteria

• {"criterion_text":"- 1.\tInability or unwillingness to adhere to the study protocol, including study procedures and oral intake of the IMP."}
• {"criterion_text":"- 10.\tHistory of primary immunodeficiency, bone marrow transplantation or solid organ transplantation."}
• {"criterion_text":"- 11.\tUse of systemic immunosuppressive medication (including > 10 mg prednisolone per day or equivalent) within 14 days prior to the first IMP administration. Note that use of immunosuppressive medications as prophylaxis in participants with contrast allergies is acceptable. Adrenal replacement corticosteroid doses > 10 mg daily prednisone equivalent are permitted, as are topical, inhaled, intra-articular or intra-nasal corticosteroids."}
• {"criterion_text":"- 12.\tParticipants with active Hepatitis B virus (HBV) hepatitis infection (defined as having a positive hepatitis B surface antigen [HBsAg] test at Screening) or Hepatitis C virus (HCV) hepatitis. Participants with resolved past HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA."}
• {"criterion_text":"- 13.\tParticipants with active HIV infection or known history of HIV infection. Participants with HIV are excluded unless CD4+ T-cell count is ≥ 350 /mm3, HIV viral load is undetectable, and the participant is on stable ART."}
• {"criterion_text":"- 14.\tActive infection requiring systemic antibacterial, antiviral or anti-fungal therapy for ≤ 7 days of first IMP administration. Note that participants on antibacterial, anti-fungal or antiviral prophylaxis are eligible."}
• {"criterion_text":"- 15.\tUncontrolled or recent history of clinically significant cardiovascular disease: Symptomatic heart failure (New York Heart Association classes II-IV), unstable angina, myocardial infarction, serious/uncontrolled/unstable cardiac arrhythmia, cerebral vascular accident, coronary/peripheral artery bypass graft surgery, transient ischaemic attack, or pulmonary embolism within 4 months prior to first IMP administration. Note that participants with small pulmonary emboli not thought to put them at higher risk may be considered eligible on a case-by-case basis, in discussion with the Sponsor."}
• {"criterion_text":"- 16.\tConfirmed Baseline QTcF > 450 msec for males and > 470 msec for females (triplicate ECG) or history of torsades de pointes or history of congenital long QT syndrome. Note that participants with an apparent prolonged QT due to bundle branch block may be considered eligible on a case-by-case basis, in discussion with the MM."}
• {"criterion_text":"- 17.\tHistory of clinically significant interstitial lung disease, or active non-infectious pneumonitis, or which may interfere with the detection or management of suspected drug-related pulmonary toxicity."}
• {"criterion_text":"- 18.\tHas had or is scheduled to have major surgery < 28 days prior to the first IMP administration. Elective surgical procedures not considered to put participants at higher risk of AEs may be allowed on a case-by-case basis, in discussion with the Sponsor."}
• {"criterion_text":"- 19.\tAny other concurrent severe and/or uncontrolled medical, surgical or psychiatric and/or social condition which, in the view of the Investigator, could compromise the participant’s safety or ability to participate in the study and make them unsuitable for participation."}
• {"criterion_text":"- 2.\tPatients with known leptomeningeal disease or untreated, symptomatic, or progressing central nervous system (CNS) metastases. Patients with treated brain metastases will be eligible if free of progression for at least 4 weeks post-CNS therapy (eg, surgery, radiotherapy), confirmed by brain MRI at Screening, and are neurologically stable (no CNS symptoms)."}
• {"criterion_text":"- 20.\tUse of other investigational medicinal products within 2 weeks or at least 5 half-lives (whichever is longer) before IMP administration."}
• {"criterion_text":"- 21.\tMust not have had a live vaccine administration ≤ 28 days prior to the first dose of the IMP."}
• {"criterion_text":"- 22.\tParticipants with known active or suspected alcohol or drug abuse that may interfere with the study in the opinion of the Investigator."}
• {"criterion_text":"- 23.\tGastrointestinal conditions that may affect oral absorption of drugs in the opinion of the Investigator, including but not restricted to gastroparesis and short bowel syndrome."}
• {"criterion_text":"- 1.\tAdditional Module B2 and B3 Specific Exclusion Criteria - Known hypersensitivity to nivolumab (OPDIVO®) or to any of the excipients listed in the Section 6.1 (List of excipients) of the OPDIVO® SmPC."}
• {"criterion_text":"- 2.\tAdditional Module B2 and B3 Specific Exclusion Criteria - Prior immunotherapy-related toxicity that led to a.\tdiscontinuation of the immunotherapy, or b.\trequired more than steroid therapy."}
• {"criterion_text":"- 3.\tAdditional Module B2 and B3 Specific Exclusion Criteria - Active or prior documented autoimmune or inflammatory disorders that, in the opinion of the Investigator, qualifies as a contraindication for nivolumab as per the Sections 4.3 (Contraindications) and 4.4 (Special warnings and precautions for use) of the OPDIVO® SmPC."}
• {"criterion_text":"- 4.\tAdditional Module B2 and B3 Specific Exclusion Criteria - History of pneumonitis or interstitial lung disease, unless resolved and free from requiring systemic steroids for ≥ 90 days and considered by the Investigator as not clinically significant, in line with safety considerations described in Section 4.8 (Undesirable effects) of the OPDIVO® SmPC."}
• {"criterion_text":"- 5.\tAdditional Module B2 and B3 Specific Exclusion Criteria - Concurrent use of systemic immunosuppressive agents that are contraindicated during treatment with nivolumab per Section 4.5 (Interaction with other medicinal products and other forms of interaction) of the OPDIVO® SmPC."}
• {"criterion_text":"- 3.\tUnresolved or unstable serious toxic side effects of prior anti-cancer therapy or radiotherapy, ie, ≥ Grade 2 per CTCAE v5.0 except fatigue, alopecia, infertility, or those relating to palliative radiotherapy within 6 weeks prior to first IMP administration. Participants with residual AEs > Grade 1 considered not clinically significant may be considered eligible on a case-by-case basis, in discussion with the Sponsor."}
• {"criterion_text":"- 4.\tConcurrent active or previous history of other malignancy within the past 2 years before first IMP administration except: a.\tMalignancy (other than in situ) treated with curative intent and with no known active disease present for ≥ 2 years before first IMP administration and felt to be at low risk of recurrence by the Investigator; b.\tAdequately treated non-melanoma skin cancer or lentigo malignant with no evidence of disease; c.\tAdequately treated in situ cancer without evidence of disease."}
• {"criterion_text":"- 5.\tReceived anti-cancer therapy (including chemotherapy, immunotherapy, radiation therapy, biologic therapy, or any investigational therapy) within 28 days or 5 half-lives of the therapeutic agent, whichever is shorter, prior to the first IMP administration. Exceptions include: \tPatients who received palliative radiotherapy given within 28 days prior to the first IMP administration may be considered eligible on a case-by-case basis, in discussion with the Sponsor. \tOngoing concomitant androgen deprivation therapy with GnRH agonist or GnRH antagonist for castration-resistant prostate cancer is permitted."}
• {"criterion_text":"- 6.\tUncontrolled symptomatic malignant effusion(s) or those requiring recurrent drainage, in the opinion of the Investigator."}
• {"criterion_text":"- 7.\tParticipants with clinically significant active autoimmune or chronic inflammatory disease that is not well controlled with standard therapy, in the opinion of the Investigator."}
• {"criterion_text":"- 8.\tGrade 3 or higher immunotherapy-induced autoimmune hepatitis."}
• {"criterion_text":"- 9.\tParticipants with: a.\tsymptomatic colitis of any grade as per CTCAE v5.0 and any non-infective aetiology within 4 weeks before first dosing. For any episodes of infective colitis, these should have resolved and patients should have completed antimicrobial treatment, if required, at least 1 week prior to IMP administration. b.\ta history of autoimmune colitis or inflammatory bowel disease, unless the condition has been resolved for > 2 years and requires no immunosuppressive therapy during this period, and/or, c.\ta history of drug-induced colitis of ≥ Grade 3 per CTCAE v5.0."}

Primary endpoints

• {"endpoint_text":"- Incidence, nature, and severity of AEs, SAEs, and TEAEs.","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- •\tIncidence, nature, and severity of AEs, SAEs, and TEAEs.","definition_or_measurement_approach":""}
• {"endpoint_text":"- •\tTumour response assessment by cross-sectional imaging: objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and progression free survival (PFS) as assessed by RECIST v1.1 and/or iRECIST (if applicable) criteria, based on Investigator assessment","definition_or_measurement_approach":"Assessed by cross-sectional imaging using RECIST v1.1 and/or iRECIST criteria as per Investigator assessment."}
• {"endpoint_text":"- •\tOverall survival (OS) as assessed during study participation and via telephone follow-ups every 3 months thereafter.","definition_or_measurement_approach":"Overall survival assessed during study and by telephone follow-ups every 3 months."}
• {"endpoint_text":"- •\tPlasma PK parameters, including but not limited to: Cmin, Cmin_ss, and accumulation ratio (RA Cmin).","definition_or_measurement_approach":"Plasma pharmacokinetic parameters measured (e.g., Cmin, Cmin_ss, accumulation ratio) per PK sampling schedule."}

Spain

Earliest CTIS Part Ii Submission Date

20-11-2025

Latest Decision Or Authorization Date

02-03-2026

Processing Time Days

102

Number Of Sites

7

Number Of Participants

70

France

Earliest CTIS Part Ii Submission Date

16-12-2025

Latest Decision Or Authorization Date

27-02-2026

Processing Time Days

73

Number Of Sites

3

Number Of Participants

25

Primary sponsor

Full Name

Pathios Therapeutics Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Novotech Clinical Research (Cyprus) Limited

Responsibilities

1; 10; 11; 12; 13; 2; 5; 6; 7

Name

Sonic Clinical Trials Pty Limited

Responsibilities

Lab kits supply and sample storage (AU)

Name

Agilex Biolabs Pty Limited

Responsibilities

4

Name

CellCarta

Responsibilities

4

Name

A.M.L.

Responsibilities

15 (Lab kits supply and sample storage (EU))

Third parties

• {"country":"Australia","full_name":"Sonic Clinical Trials Pty Limited","duties_or_roles":"Lab kits supply and sample storage (AU)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Australia","full_name":"Gnomix","duties_or_roles":"4","organisation_type":"Industry"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Catalent San Diego Inc.","duties_or_roles":"14; 15 (Manufacture of IMP, Stability of IMP)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"A.M.L.","duties_or_roles":"15 (Lab kits supply and sample storage (EU))","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Cyprus","full_name":"Novotech Clinical Research (Cyprus) Limited","duties_or_roles":"1; 10; 11; 12; 13; 2; 5; 6; 7","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"Agilex Biolabs Pty Limited","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CellCarta Biosciences","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"15 (Storage of IMP, Distribution - EU, Labelling of IMP)","organisation_type":"Pharmaceutical company"}
• {"country":"Australia","full_name":"AGRF","duties_or_roles":"4","organisation_type":"Industry"}
• {"country":"United States","full_name":"Scarritt Group Inc.","duties_or_roles":"15 (Reimbursement)","organisation_type":"Non-Pharmaceutical company"}