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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: ICT01
* Drug: Proleukin Injectable Product
* Drug: Pembrolizumab injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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: metastatic colorectal cancer (CRC): metastatic ovarian cancer: metastatic castration-resistant prostate cancer (mCRPC) 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) Any malignancy of γ9δ2 T cell origin Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment Treatment with investigational drugs within 28 days before study treatment Systemic steroids at a daily dose of > 10 mg of prednisone, > 2 mg of dexamethasone or equivalent, for the last 28 days and ongoing 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 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. Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy Primary or secondary immune deficiency Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment Patients with contraindication to IL-2 treatment according to the SmPC/package insert

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 2 ICT01 + Low dose SC IL-2 + Pembrolizumab<br>The best regimen of ICT01+IL-2 will be combined with pembrolizumab at the approved dose since the combination of ICT01+IL-2 induces upregulation of PD-1 on g9d2 T cells and in the TME. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;Drug: Pembrolizumab injection<br>* 200mg administered following ICT01 + LDSC IL-2 over 30 min Q3W<br>|
| Experimental: Dose level 2 ICT01 + Low dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|
| Experimental: Dose Level 1 ICT01 + High dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|
| Experimental: Dose level 1 ICT01 + Low dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|
| Experimental: Dose level 3 ICT01 + Low dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|
| Experimental: Dose level 4 ICT01 + Low dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|
| Experimental: Dose level 5 ICT01 + Low dose SC IL-2<br>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. | Drug: ICT01<br>* anti-BTN3A mAb IV Q3W<br>Drug: Proleukin Injectable Product<br>* 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles<br>* Other names: IL-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-Emergent Adverse Events | Incidence and severity of adverse events related to study treatment | 1 year | 

Secondary Outcome Measures

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