LTX-315 in Patients With Transdermally Accessible Tumours as Monotherapy or Combination With Ipilimumab or Pembrolizumab

This is an interventional treatment trial for Cancer focused on measuring Transdermal accessible tumours Read More

Inclusion Criteria:

Arm A: (Recruitment completed)

Arm B:

• Unresectable metastatic disease (any tumor type) and conventional anti-tumor treatment is not appropriate.
• Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection between 1-3 cm longest diameter and one bystander lesion (non-injected).

Arm C:

• Have unresectable/metastatic diagnosis of malignant melanoma (histologically confirmed).
• Have at least one available lesion (cutaneous, sub-cutaneous, oral or lymph node) for injection and biopsy which is between 1 and 3 cm in longest diameter.
• Have had previous treatment with an anti-PD-1 antibody (as monotherapy or as part of combination (any combination) as 1st or 2nd line metastatic treatment).

Arm D:

• Have unresectable/metastatic diagnosis of triple negative breast cancer (histologically confirmed).
• Have at least one available lesion (cutaneous, sub-cutaneous or lymph node) for injection and biopsy with a minimum longest diameter of 1 cm.
• Have received between one and 4 prior systemic treatments for metastatic triple negative breast cancer.

All arms:

• Be willing to undergo repeat tumour biopsy and/or tumour resection procedures.
• Have an ECOG Performance status (PS): 0 - 1.

• Meet the following laboratory requirements:

  1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  2. Absolute lymphocyte count ≥ 0.8 x 109/L
  3. Platelet count ≥ 75 x 109/L
  4. Haemoglobin ≥ 9.0 g/dL
  5. aPTT/PT within the institution's normal range
  6. Total bilirubin level ≤ 1.5 x ULN
  7. ASAT and ALAT ≤ 2.5 x ULN (≤5 x ULN if liver metastasis present)
  8. Creatinine ≤ 1.5 x ULN

  9. Albumin ≥ 30 g/L

     Exclusion Criteria:

     Arm A: (Completed)

     Arm B:

• Have a history of systemic auto-immune disease requiring anti-inflammatory or immunosuppressive therapy within the last 3 months. Patients with history of autoimmune thyroiditis are eligible provided the patient requires only thyroid hormone replacement therapy and disease has been stable for ≥ 1 year.

Arm C:

• Have had prior therapy with ipilimumab or any other anti-CTLA-4 monoclonal antibody.
• Have had BRAF/MEK inhibitors administered within 2 weeks prior to the study drug administration.
• Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; have a history of severe immune-related adverse reaction from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.

Arm D:

• Have had prior therapy with an anti-PD-1 or anti-PD-L1 monoclonal antibody.
• Have received cancer immunotherapy within 2 weeks prior to study drug administration or have not recovered from adverse events (to ≤ CTCAE grade 1) due to such agents.
• Have active systemic autoimmune disease; have had prior pneumonitis; have a history of severe hypersensitivity to another monoclonal antibody; are receiving immunosuppressive therapy; and have a history of severe immune-related adverse reactions from treatment with a monoclonal antibody, defined as any Grade 4 or 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks.

All arms:

• Have received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to study drug administration, or have not recovered from adverse events (≤ CTCAE grade 1) due to agents administered more than 4 weeks earlier. Palliative radiotherapy to non-target lesions within 4 weeks prior to study drug administration is allowed.
• Are currently taking any agent with a known effect on the immune system. Patients are allowed to be on a stable dose of corticosteroids (up to 10 mg daily prednisolone or equivalent) for at least 2 weeks prior to study drug administration (please see Appendix IV for prohibited medications).

• Have any other serious illness or medical condition such as, but not limited to:

  1. Uncontrolled infection or infection requiring antibiotics
  2. Uncontrolled cardiac failure: Classification III or IV (New York Heart Association)
  3. Uncontrolled systemic and gastro-intestinal inflammatory conditions
  4. Bone marrow dysplasia
• Have a known history of positive tests for HIV/AIDS, or have active hepatitis B or C (based on serology).

• Are expected to need any other anti-cancer therapy or immunotherapy to be initiated during the study period.

  15. Have clinically active or unstable CNS metastases as assessed by the treating physician.