An Open Label Dose Finding Study of PTT-4256 in Patients With Solid Tumours (RAISIC-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pathios Therapeutics Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Decision date (initial)

2026-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2025-522944-41-00

ClinicalTrials.gov

NCT06634849

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety, Pharmacodynamic

To determine the safety and tolerability of PTT-4256 in participants in specified tumour type, either as a monotherapy or in combination with an approved inhibitor of PD-1/PD-L1.

Secondary objectives 3

1. • To confirm the safety of RP2D/OBD of PTT-4256 as a monotherapy and/or in combination with an approved inhibitor of PD-1/PD-L1.
2. • To assess the preliminary efficacy of PTT-4256 in specific tumour type(s) either as a monotherapy and/or in combination with an approved inhibitor of PD-1/PD-L1 in expansion cohorts.
3. • To characterise the plasma PK of PTT-4256 in expansion cohort(s).

Conditions and MedDRA coding

Solid Tumours

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 22

1. 1. ≥ 18 years of age at the time of consent.
2. 2. Participant has given written informed consent to participate in the study and is able and willing to adhere to the study protocol.
3. 3. Participant has measurable disease per RECIST v1.1.
4. 4. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
5. 5. Participant has an estimated life expectancy of at least 3 months in the opinion of the Investigator.
6. 6. Adequate 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): • Haemoglobin ≥ 8.5 g/dL, • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, • Platelet count ≥ 90 x 109/L, • Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN), (or where ≤ 2 × ULN with known hepatobiliary metastases or Gilbert’s syndrome), • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN if liver metastases are present), • Estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 (calculated using Cockcroft-Gault).
7. 7. Females: a. must not be pregnant or lactating, and b. must use acceptable, highly effective contraception from Screening until:  90 days after last IMP administration (Module A and Module B1) or  5 months after last IMP administration (Module B2 and Module B3). Effective forms of contraception are defined in Section 7.3.2. c. females 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. women 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: - at least 90 days after the last IMP administration (Module A and Module B1) or - at least 5 months after the last IMP administration (Module B2 and Module B3). WOCBP are defined in Section 7.3.2, or e. women 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).
8. 8. Males: a. must be surgically sterile (> 6 months since vasectomy with confirmation of no viable sperm), or b. males 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. if 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. Males must not donate sperm from the first dose of IMP until at least 90 days after the last dose of IMP administration.
9. 1. Additional Module B1 Specific Inclusion Criteria - Participant has histologically confirmed diagnosis of unresectable locally advanced or metastatic RCC including ccRCC or pRCC.
10. 2. Additional 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.
11. 3. Additional 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.
12. 1. Additional Module B2 Specific Inclusion Criteria - Participant has histologically confirmed diagnosis of unresectable locally advanced or metastatic ccRCC.
13. 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.
14. 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.
15. 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.
16. 5. Additional 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®).
17. 1. Additional 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.
18. 2. Additional 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.
19. 3. Additional 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.
20. 4. Additional 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.
21. 5. Additional 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.
22. 6. Additional 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®).

Exclusion criteria 28

1. 1. Inability or unwillingness to adhere to the study protocol, including study procedures and oral intake of the IMP.
2. 2. Patients 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).
3. 3. Unresolved 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.
4. 4. Concurrent active or previous history of other malignancy within the past 2 years before first IMP administration except: a. Malignancy (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. Adequately treated non-melanoma skin cancer or lentigo malignant with no evidence of disease; c. Adequately treated in situ cancer without evidence of disease.
5. 5. Received 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:  Patients 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.  Ongoing concomitant androgen deprivation therapy with GnRH agonist or GnRH antagonist for castration-resistant prostate cancer is permitted.
6. 6. Uncontrolled symptomatic malignant effusion(s) or those requiring recurrent drainage, in the opinion of the Investigator.
7. 7. Participants with clinically significant active autoimmune or chronic inflammatory disease that is not well controlled with standard therapy, in the opinion of the Investigator.
8. 8. Grade 3 or higher immunotherapy-induced autoimmune hepatitis.
9. 9. Participants with: a. symptomatic 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. a 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. a history of drug-induced colitis of ≥ Grade 3 per CTCAE v5.0.
10. 10. History of primary immunodeficiency, bone marrow transplantation or solid organ transplantation.
11. 11. Use 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.
12. 12. Participants 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.
13. 13. Participants 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.
14. 14. Active 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.
15. 15. Uncontrolled 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.
16. 16. Confirmed 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.
17. 17. History 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.
18. 18. Has 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.
19. 19. Any 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.
20. 20. Use of other investigational medicinal products within 2 weeks or at least 5 half-lives (whichever is longer) before IMP administration.
21. 21. Must not have had a live vaccine administration ≤ 28 days prior to the first dose of the IMP.
22. 22. Participants with known active or suspected alcohol or drug abuse that may interfere with the study in the opinion of the Investigator.
23. 23. Gastrointestinal conditions that may affect oral absorption of drugs in the opinion of the Investigator, including but not restricted to gastroparesis and short bowel syndrome.
24. 1. Additional 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.
25. 2. Additional Module B2 and B3 Specific Exclusion Criteria - Prior immunotherapy-related toxicity that led to a. discontinuation of the immunotherapy, or b. required more than steroid therapy.
26. 3. Additional 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.
27. 4. Additional 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.
28. 5. Additional 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence, nature, and severity of AEs, SAEs, and TEAEs.

Secondary endpoints 4

1. • Incidence, nature, and severity of AEs, SAEs, and TEAEs.
2. • Tumour 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
3. • Overall survival (OS) as assessed during study participation and via telephone follow-ups every 3 months thereafter.
4. • Plasma PK parameters, including but not limited to: Cmin, Cmin_ss, and accumulation ratio (RA Cmin).

Investigational products

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

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pathios Therapeutics Limited

Sponsor organisation

Pathios Therapeutics Limited

Address

99 Park Drive, Milton Milton

City

Abingdon

Postcode

OX14 4RY

Country

United Kingdom

Scientific contact point

Organisation

Pathios Therapeutics Limited

Contact name

Pathios Therapeutics

Public contact point

Organisation

Pathios Therapeutics Limited

Contact name

Pathios Therapeutics

Third parties 11

Locations

2 EU/EEA countries · 10 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 18 files

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

Application history

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