Intratumoral Injection of IP-001 Following Thermal Ablation in Patients With Advanced Solid Tumors.

Prior treatment

• Patients who have received chemotherapy, radiotherapy, immunotherapy, or concurrent or recent treatment with any other investigational agents within 21 days (7 days for single fraction of palliative radiotherapy, 42 days for nitrosoureas or mitomycin C) prior to registration.
• Patients who have not recovered to ≤ CTCAE grade 1 from all side effects of prior therapies except for residual toxicities, such as alopecia, which do not pose an ongoing medical risk.
• Patients with prostate cancer must have discontinued anti-androgens (e.g., bicalutamide, nilutamide) for at least 6 weeks prior to registration; chemical castration with luteinizing hormone-releasing hormone analogues must be continued or patients must be surgically castrated.
• Concomitant treatment with systemic corticosteroids (daily dose of 10 mg prednisolone or equivalent is allowed) or other immunosuppressive therapy (e.g. methotrexate).
• Oral anti-coagulation with vitamin K antagonists (e.g. phenprocoumon, warfarin) and heparin, including therapeutically dosed low molecular weight heparins (LMWH) which cannot be stopped 24 hours prior to trial treatment (low dose aspirin allowed) and bleeding diathesis

Other illness

• Malignant primary brain tumors, or clinically unstable symptoms from brain metastases or leptomeningeal disease, indicative of active disease.
• Patients with a previously treated malignancy, when the risk of the prior malignancy interfering with either safety or efficacy endpoints is not very low.
• Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B Viral infection or any uncontrolled active systemic infection (\> CTCAE grade 2) requiring intravenous (iv) antimicrobial treatment
• Serious autoimmune disease (e.g. systemic lupus erythematodes) which is judged to reduce an anti-tumor immune response.
• Known allergic reaction to shellfish, crabs, crustaceans, or any trial components, including medical device, used in trial treatment.
• Any other serious underlying medical, psychological, familial or geographical condition, which in the judgment of the investigator may limit compliance with the planned staging, treatment and follow-up, or place the patient at high risk from treatment-related complications.

Lab values

• Severe or uncontrolled cardiovascular disease (congestive heart failure New York Heart Association classificationIII or IV), unstable angina pectoris, history of myocardial infarction within the last six months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-prolongation, uncontrolled hypertension .

• Written informed consent according to Swiss law and ICH/GCP regulations before registration.
• Part 1: - 'All comer' Patients with either histologically or cytologically confirmed advanced or recurrent solid tumor cancer who failed standard therapy, are not eligible for standard therapy, or for whom no effective standard therapy is available and not requiring fast responses.
• Part 2, Cohort 1 - Sarcoma cohort: Patients with either histologically or cytologically confirmed advanced or recurrent soft tissue sarcoma who failed standard therapy, are not eligible for standard therapy or for whom no effective standard therapy is available.
• Part 2, Cohort 2 - Melanoma cohort: Patients with either histologically or cytologically confirmed advanced or recurrent melanoma who failed standard therapy (including a BRAF inhibitor for BRAF-mutant patients), are not eligible for standard therapy or for whom no effective standard therapy is available and have LDH \< ULN.
• Presence of at least one tumor lesion that is laser ablation-accessible, with a minimum size of 1.0 cm and located (typically subcutaneously) that it can be treated with Ablation + IP-001 without risk of skin necrosis or serious damage to other adjacent vital and healthy tissue. This tumor lesion may either belong to the skin, lymph nodes, muscles or subcutaneous tissue.
• Measurable or evaluable disease, determined with the most suitable imaging method (CT, PET-CT or MRI), according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• No evidence of CNS progression for at least 4 weeks after completion of CNS-directed therapy as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period.
• Age ≥ 18 years
• WHO performance status 0-2
• Bone marrow function: neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 90 g/L
• Hepatic function: bilirubin ≤ 1.5 x ULN, aspartate transaminase (AST) and alanine transaminase ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in presence of liver metastasis)
• Renal function: estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73m2 (according to Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula)
• Women with child-bearing potential are using effective contraception, are not pregnant or lactating and agree not to become pregnant during trial treatment and for an additional 90 days after the last dose of investigational drug. Women of childbearing potential must have a negative serum human chorionic gonadotropin (hCG) pregnancy test before inclusion.
• Men agree not to donate sperm or to father a child during trial treatment and until 90 days after the last dose of investigational drug.