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

Phase 1
Active, not recruiting
Conditions
Solid Tumor, Adult
Interventions
Registration Number
NCT05307874
Lead Sponsor
ImCheck Therapeutics
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 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
56
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

      1. 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose level 2 ICT01 + Low dose SC IL-2Proleukin Injectable ProductFor 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.
Dose level 1 ICT01 + Low dose SC IL-2ICT01For 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.
Dose level 2 ICT01 + Low dose SC IL-2ICT01For 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.
Dose Level 1 ICT01 + High dose SC IL-2ICT01For 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.
Dose level 4 ICT01 + Low dose SC IL-2ICT01For 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.
Dose level 5 ICT01 + Low dose SC IL-2ICT01For 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.
Dose level 5 ICT01 + Low dose SC IL-2Proleukin Injectable ProductFor 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.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 3 ICT01Proleukin Injectable ProductICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Dose level 2 ICT01 + Low dose SC IL-2 + PembrolizumabProleukin Injectable ProductICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Dose Level 1 ICT01 + High dose SC IL-2Proleukin Injectable ProductFor 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.
Dose level 3 ICT01 + Low dose SC IL-2ICT01For 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.
Dose level 1 ICT01 + Low dose SC IL-2Proleukin Injectable ProductFor 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.
Dose level 4 ICT01 + Low dose SC IL-2Proleukin Injectable ProductFor 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.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 2 ICT01ICT01ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 2 ICT01Proleukin Injectable ProductICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Dose level 3 ICT01 + Low dose SC IL-2Proleukin Injectable ProductFor 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.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Booster Dose level 3 ICT01ICT01ICT01 IV is given on Day 1 of every 21-day cycle and on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Dose level 2 ICT01 + Low dose SC IL-2 + PembrolizumabICT01ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Dose level 2 ICT01 + Low dose SC IL-2 + PembrolizumabPembrolizumab injectionICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Dose level 4 ICT01 + Low dose SC IL-2 + PembrolizumabICT01ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Dose level 4 ICT01 + Low dose SC IL-2 + PembrolizumabProleukin Injectable ProductICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Dose level 4 ICT01 + Low dose SC IL-2 + PembrolizumabPembrolizumab injectionICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. SC IL-2 is administred Days 1-5 of cycles 1/2/3 only.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01ICT01ICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01Proleukin Injectable ProductICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Primer Dose level 2 ICT01+ Low dose SC IL-2 + Pembrolizumab + Booster Dose level 2 ICT01Pembrolizumab injectionICT01 IV and Pembrolizumab are given on Day 1 of every 21-day cycle. ICT01 IV is given on day 8 of Cycles 1-3. SC IL-2 is administered on Days 1-5 of Cycles 1/2/3 only.
Primary Outcome Measures
NameTimeMethod
Treatment-Emergent Adverse Events1 year

Incidence and severity of adverse events related to study treatment

Secondary Outcome Measures
NameTimeMethod
Change from baseline in the number of circulating g9d2 T cellsCycle Days 8 & 15 for the first 3 cycles

flow cytometry measurement of circulating and intratumoral g9d2 T cells

Disease Control Rate1 year

Stable disease or better by RECIST1.1

Trial Locations

Locations (5)

IUCT Oncopole Claudius Regaud

🇫🇷

Toulouse, France

University Carl Gustav Carus

🇩🇪

Dresden, Germany

Universitätsklinikum Wuerzburg

🇩🇪

Wuerzburg, Germany

The Institute of Cancer Research

🇬🇧

Sutton, United Kingdom

Institute Gustave Roussy

🇫🇷

Paris, France

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