Safety and Preliminary Efficacy of MBS8(1V270) in Cancer Patients With Advanced Solid Tumours

The Phase I trial is evaluating safety, tolerability, pharmacokinetics and preliminary efficacy of MBS8(1V270) in subjects with advanced solid tumours. The trial is designed to provide data for further clinical development of MBS8(1V270)

Stage I Inclusion Criteria 1. Male or female aged ≥18 years. 2. Diagnosis of a histologically or cytologically confirmed solid tumour that was advanced and with progression. No standard treatment existed, or the participant refused standard treatment. Experimental immunotherapy appeared as a feasible exploratory treatment option as per Investigator's assessment. 3. Tumour lesion(s) accessible to serial biopsies. 4. Was willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and tumour biopsies. Mandatory Baseline and on-treatment tumour biopsies were required. However, a biopsy may have been omitted if the procedure was deemed medically unsafe or not feasible, based on the Investigator's clinical judgment and after discussion with the Medical Monitor (or Sponsor's designee). 5. Measurable disease according to RECIST v1.1. Previously irradiated lesions were measurable if subsequent progression was documented. 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. 7. Life expectancy \>3 months as assessed by the Investigator. 8. Adequate bone marrow, cardiopulmonary, renal and hepatic functions: • Haemoglobin ≥5.6 mmol/L (≥90 g/dL) (without transfusion or erythropoietin therapy within 4 weeks prior to therapy) • Neutrophils ≥1.5×109/L, without growth factor stimulation within 3 weeks prior to the blood test • Platelet count ≥75×109/L • Serum creatinine ≤1.25×ULN or creatinine clearance ≥50 mL/min (by CKD-EPI formula) • Hepatic function: AST and ALT ≤2.5×ULN; (5×ULN in the case of liver metastases); bilirubin ≤1.5×ULN except in the case of Gilbert's syndrome and 2×ULN in the case of liver metastases. 9. All participants of childbearing potential (defined as \10 mg/day prednisone-equivalent within 14 days before C1D1. Note: Physiologic/replacement doses (e.g., adrenal insufficiency) up to 10 mg/day prednisone-equivalent, topical, inhaled, intra-articular, intranasal, or ophthalmic steroids are allowed. 8. All participants of childbearing potential (defined as \10 mg prednisone per day or equivalent, except topical or inhaled) during the last 2 years prior to the first dose of MBS8(1V270). Stage II General Exclusion Criteria The following general exclusion criteria apply to all participants unless cohort criteria specify otherwise. 1. Uncontrolled intercurrent illness: active infection requiring IV therapy, uncontrolled congestive heart failure, unstable angina, significant arrhythmia, recent myocardial infarction (≤6 months), or uncontrolled hypertension. 2. Known active HIV with uncontrolled viraemia, active hepatitis B virus (HBV)/hepatitis C virus (HCV) with high viral load (HBV \>20,000 IU/mL and HCV \>800,000 IU/mL) despite therapy (enrol per local guidelines, if controlled). 3. Pregnant or breastfeeding. 4. Second malignancy requiring active therapy (except adequately treated non-melanoma skin cancers, in situ cancers, or malignancies in remission ≥2 years) 5. Allergy/hypersensitivity to trial drug components. 6. Live vaccines within 28 days prior to C1D1. 7. QTcF \>500 ms. 8. Any condition that, in the Investigator's judgement, compromises safety or compliance. 9. Active autoimmune disease requiring systemic treatment in the past 2 years (topicals/inhaled/physiologic replacement allowed). 10. Any prior exposure to systemic or IT immunotherapy (except tebentafusp, pembrolizumab, nivolumab, ipilimumab, and relatlimab), but including Montanide, TLR7, TLR8, and TLR9 agonists, polyinosinic:polycytidylic acid, cationic adjuvant formulation, messenger ribonucleic acid -based vaccines, T cell therapy, and oncolytic viruses. 11. Participants who have been previously treated with experimental anti-cancer vaccines. Stage II - Cohort A (Cutaneous Melanoma; Pembrolizumab in Combination with MBS8(1V270)) Specific Exclusion Criteria The following exclusion criteria apply specifically to Stage II - Cohort A. 12A. Prior life-threatening or Grade ≥3 immune-related toxicity to immune checkpoint inhibitors requiring permanent discontinuation of these therapies (exception: controlled endocrinopathies on replacement). 13A. Interstitial lung disease/pneumonitis (current or history requiring steroids). 14A. Concurrent anti-cancer therapy other than trial-allowed supportive care. 15A. Histologically/cytologically confirmed cutaneous acral melanoma and mucosal melanoma. Stage II - Cohort B (Uveal Melanoma, MBS8(1V270) Monotherapy) Specific Exclusion Criteria The following exclusion criteria apply specifically to Stage II - Cohort B. 12B. Active, uncontrolled hepatic dysfunction not attributable to tumour (e.g., acute hepatitis). 13B. Any contraindication specific to MBS8(1V270) per IB (e.g., known hypersensitivity to excipients, cohort-specific risk factors). 14B. Brain metastases.