Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors (EVICTION-2)

• ClinicalTrials.gov Identifier: NCT05307874
• Recruitment Status: Recruiting
• First Posted: April 1, 2022
• Last Update Posted: October 7, 2022
• Sponsor: ImCheck Therapeutics
• Collaborators: ILife Consulting; Exystat
• Information provided by (Responsible Party): ImCheck Therapeutics

Tracking Information

• First Submitted Date: March 24, 2022
• First Posted Date: April 1, 2022
• Last Update Posted Date: October 7, 2022
• Actual Study Start Date: April 19, 2022
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 24, 2022)

Treatment-Emergent Adverse Events [ Time Frame: 1 year ]

Incidence and severity of adverse events related to study treatment

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2022)

• Change from baseline in the number of circulating g9d2 T cells [ Time Frame: Cycle Days 8 & 15 for the first 3 cycles ]
  flow cytometry measurement of circulating and intratumoral g9d2 T cells
• Disease Control Rate [ Time Frame: 1 year ]
  Stable disease or better by RECIST1.1

Original Secondary Outcome Measures (submitted: March 24, 2022)

• Change from baseline in the number of circulating g9d2 T cells [ Time Frame: 7 days post each dose for the first 3 cycles ]
• Disease Control Rate [ Time Frame: 1 year ]
  Stable disease or better by RECIST1.1

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors
• Official Title: A Two-part, Open-label, Clinical Study to Assess the Safety, Tolerability and Activity of Intravenous Doses of ICT01 in Combination With Low-dose Subcutaneous Interleukin-2 in Patients With Advanced Solid Tumors (EVICTION-2)

Brief Summary

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, which will be supported by statistical power calculations once the indications are selected. The start of Part 2 will require an amendment to confirm the indication(s) and dosing regimen(s), which will be based on the review of Part 1 data and recommendations by the SRC. The primary objective of Part 2 is to demonstrate the efficacy of the combination regimen based on RECIST1.1.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor, Adult

Intervention

• Drug: ICT01
  anti-BTN3A mAb
• Drug: Proleukin Injectable Product
  Low dose SC IL-2
  Other Name: IL-2

Study Arms

• Experimental: Dose Level 1 ICT01 + Low dose SC IL-2
  c
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 2 ICT01 + Low dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose Level 1 ICT01 + High dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 2 ICT01 + High dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 3 ICT01 + Low dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 3 ICT01 + High dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 4 ICT01 + Low dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product
• Experimental: Dose level 4 ICT01 + High dose SC IL-2
  For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.
  Interventions:

  • Drug: ICT01
  • Drug: Proleukin Injectable Product

• Publications *: De Gassart A, Le KS, Brune P, Agaugue S, Sims J, Goubard A, Castellano R, Joalland N, Scotet E, Collette Y, Valentin E, Ghigo C, Pasero C, Colazet M, Guillen J, Cano CE, Marabelle A, De Bonno J, Hoet R, Truneh A, Olive D, Frohna P. Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vgamma9Vdelta2 T cell-mediated antitumor immune response. Sci Transl Med. 2021 Oct 20;13(616):eabj0835. doi: 10.1126/scitranslmed.abj0835. Epub 2021 Oct 20.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 24, 2022): 75
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

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)

      2) Willingness to undergo baseline and 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. 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Paul Frohna, MD, PhD; +33698465644; paul.frohna@imcheck.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05307874
• Other Study ID Numbers: ICT01-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ImCheck Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: ImCheck Therapeutics
• Original Study Sponsor: Same as current

Collaborators

• ILife Consulting
• Exystat

Investigators

• Study Director: Paul FROHNA, MD, PhD; ImCheck Therapeutics

• PRS Account: ImCheck Therapeutics
• Verification Date: October 2022