LYTIX

A phase I, open-label, multi-arm, multi-centre, multi-dose, dose escalation study of LTX-315 in Patients With Transdermally Accessible Tumours as Monotherapy or Combination With Ipilimumab or Pembrolizumab. PI: Pål Fr. Brunsvig.

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

Contact information: Pål Fr. Brunsvig, PFB(a)ous-hf.no