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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Imcheck Therapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

4 May 2022 → 10 Oct 2025

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-514758-65-00

EudraCT number

2021-005110-34

ClinicalTrials.gov

NCT04243499

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacodynamic, Dose response, Safety

Part I:Characterize the overall safety and tolerability profile of a range of intravenous (IV) doses of ICT01 in combination with low-dose subcutaneous (LDSC) IL-2 in patients with advanced solid tumors and in combination with LDSC-IL-2 and pembrolizumab in patients with advanced melanoma or pancreatic ductal adenocarcinoma (PDAC).

Part II:Characterize the preliminary anti-tumor activity according to RECIST of IV ICT01 in combination with LDSC IL-2 in patients with a specific solid tumor indication with or without pembrolizumab (up to 2 indications for Part 2 will be determined after Part 1).

Secondary objectives 4

1. Part I:1. Characterize the pharmacodynamic (PD) activity of ICT01 in combination with LDSC IL-2 to increase the number and activation status of γ9δ2 T cells in the blood and tumors of patients with advanced solid tumors and in combination with LDSC-IL-2 and pembrolizumab in patients with advanced melanoma or PDAC.
2. Part II:1. Characterize the overall safety and tolerability of IV ICT01 in combination with LDSC IL-2 in patients with a specific solid tumor indication with or without pembrolizumab.
3. Part I:2. Characterize the preliminary anti-tumor activity according to Response Evaluation Criteria In Solid Tumors (RECIST) of a range of IV doses of ICT01 in combination with LDSC IL-2 in patients with advanced solid tumors and in combination with LDSC-IL-2
4. Part II:2. Characterize the PD activity of ICT01 in combination with LDSC IL-2 with or without pembrolizumab to increase the number and activation status of γ9δ2 T cells in the blood and tumors of patients with a specific solid tumor indication.

Conditions and MedDRA coding

metastatic castration-resistant prostate cancer (mCRPC)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1) Male or female aged ≥18 years 2) Voluntarily signed written informed consent before performance of any study-related screening procedures 3) 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: a. metastatic colorectal cancer (mCRC)i. patients must have progressed after receiving a fluoropyrimidine, oxaliplatin, and irinotecan and an antiangiogenic agent ii. patients with tumors known to be microsatellite instability-high (MSI-H), prior therapy with a checkpoint inhibitor is required if they were clinically able to receive it iii. patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type should have received anti-EGFR therapy. b. metastatic ovarian cancer: i. patients must be platinum resistant and must have had at least one treatment line after being resistant to platinum-based chemotherapy c. metastatic castration-resistant prostate cancer (mCRPC) d. metastatic pancreatic ductal adenocarcinoma (PDAC) e. metastatic or unresectable refractory melanoma with primary resistance following at least 6 weeks of prior CPI treatment, defined as best response of progressive disease or SD of short duration (lasting less than 6 months), as per Society for Immunotherapy of Cancer [SITC] Immunotherapy Resistance Taskforce [Kluger et al 2020]). Patients must have no available standard of care or treatment with potential survival benefit for their disease, as determined by the treating Investigator. Melanoma patients who have proto-oncogene B Raf (BRAF) V600E or V600K mutations must have received prior combination BRAF and mitogen-activated protein kinase (MEK) inhibitor therapy unless they have contraindications, as determined by the treating Investigator. 4) Availability of baseline tumor biopsy and willingness to undergo on-study tumor biopsies5) Eastern Cooperative Oncology Group (ECOG) performance status ≤1 6) Life expectancy >3 months as assessed by the Investigator 7) Clinical laboratory assessments: a. Hematology: - Hemoglobin ≥8.5 g/dL (equal to 5.28 mmol/L; transfusion dependent or independent); - platelet count ≥100 × 109/L; - lymphocyte count ≥0.5 × 109/L; - absolute neutrophil count ≥1.0 × 109/L; - White Blood Count (WBC) ≥4 × 109/L b. Liver enzymes: - aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN) (<5 × ULN in the case of liver metastases);- bilirubin ≤1.5 × ULN (<2 × ULN in case of liver metastases); c. Renal function: serum creatinine <1.5 × ULN or creatinine clearance ≥50 mL/min (Cockcroft and Gault) for serum creatinine ≥1.5x ULN. 8) Pulse oximetry of 95% or higher at rest, unless patient has chronic lung disease where 90% or higher at rest is acceptable 9) Contraceptives measures10) Women must not be breastfeeding 11) At least 1 measurable lesion per RECIST

Exclusion criteria 1

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, or 5 half-lives, whichever is longer, 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 ≥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 IV antibiotic or antiviral treatment 10) Known/suspected hypersensitivity against ICT01, human or humanized IgGs, IL-2 (Proleukin®), pembrolizumabor their excipients 11) Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) 12) Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry 13) Dementia or altered mental status that would prohibit informed consent 14) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator 15) Active drug or alcohol abuse as assessed by the Investigator 16) Patients with uncontrolled and symptomatic brain metastases or seizure disorders. Patient with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 4 weeks 17) Patients who have received vaccination with a live-attenuated vaccine within 30 days prior to study treatment initiation 18) Patients with contraindications to IL-2 according to the Summary of Product Characteristics (SmPC), including organ allografts and pre-existing severe major organ dysfunction. 19) For cohorts 13, 14 and 15 in combination with Pembrolizumab: patients with prior allogeneic HSCT or solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1. The primary objective of safety and tolerability will be evaluated in this study by the incidence, severity, and relationship of the following endpoints during the study: DLTs, TEAEs, fatal TEAEs, TESAEs, TEAEs leading to discontinuation of study treatment or treatment modifications; and incidence and severity of clinically significant findings on clinical laboratory tests, vital signs, ECGs, and physical examinations (Key secondary endpoint in Part 2).
2. Part 2. Disease control rate (DCR) comprising patients with stable disease, partial response, or complete response per RECIST.

Secondary endpoints 2

1. In Part 1 the preliminary anti-tumor activity endpoint will be the DCR as per RECIST. If appropriate, objective response rate (ORR; the sum of CR + PR), time-to-progression (TTP), progression-free survival (PFS) and overall survival (OS) will also be analyzed as endpoints. The iRECIST will be considered exploratory and used for treatment decisions.
2. In Part 2, key secondary endpoints include the safety and tolerability (same endpoints as for Part 1).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Imcheck Therapeutics

Sponsor organisation

Imcheck Therapeutics

Address

9e Arrondissement, 31 Chemin Joseph Aiguier 31 Chemin Joseph Aiguier

City

Marseille

Postcode

13009

Country

France

Scientific contact point

Organisation

Imcheck Therapeutics

Contact name

Lemmens

Public contact point

Organisation

Imcheck Therapeutics

Contact name

Lemmens

Third parties 8

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications