Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients with Advanced Solid Tumors

This is a phase I/IIa, two-part, open-label study to characterize the safety, tolerability, pharmacodynamics, and antitumor activity of ICT01 in combination with LDSC IL-2 in patients with advanced-stage solid tumors.

Part 1 will be a dose escalation of IV ICT01 administered on the first day of every 21-day cycle (CnD1) to patients with advanced-stage solid tumors in combination with LDSC IL-2 (Proleukin®) administered daily on days 1-5 of cycles 1-3 (C1-3D1-5). Objectives of part 1 are to characterize the safety of the combination regimen and determine the RP2D for Part 2.

Part 2 will comprise a maximum of 2 indications and 2 combination dosing regimens of ICT01 +LDSC IL-2, which will be supported by statistical power calculations once the indications are selected. The final regimen will be ICT01 + LDSC IL-2 + Pembrolizumab on a Q3W cycle. The primary objective of Part 2 is to demonstrate the efficacy of the combination regimen based on RECIST1.1 in one or more solid tumor indications.


Eligibility Criteria:
Inclusion Criteria:

1. Relapsed/refractory patients who have failed at least 2 lines of systemic therapy or who failed first line therapy and are intolerant of or have a contraindication to the standard second line of therapy with histologically or cytologically confirmed diagnosis of:

   1. metastatic colorectal cancer (CRC):
   2. metastatic ovarian cancer:
   3. metastatic castration-resistant prostate cancer (mCRPC)
   4. metastatic pancreatic ductal adenocarcinoma (PDAC)
   5. metastatic or unresectable refractory melanoma

      2) Availability of baseline tumor biopsy and willingness to undergo on-study tumor biopsies 3) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 4) Life expectancy \> 3 months as assessed by the Investigator 5) At least 1 measurable lesion per RECIST1.1

      Exclusion Criteria:
      1. Any malignancy of γ9δ2 T cell origin
      2. Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment
      3. Treatment with investigational drugs within 28 days before study treatment
      4. Systemic steroids at a daily dose of \> 10 mg of prednisone, \> 2 mg of dexamethasone or equivalent, for the last 28 days and ongoing
      5. Patients with rapidly progressing disease defined as advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (e.g., during Screening Period/ treatment washout) that includes patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement
      6. Ongoing immune-related adverse events (irAEs) ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
      7. Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy
      8. Primary or secondary immune deficiency
      9. Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment
      10. Patients with contraindication to IL-2 treatment according to the SmPC/package insert