ICT01 for Advanced-stage relapsed/refractory cancer|Malignant solid tumor|Hematological malignancy

Inclusion criteria

• {"criterion_text":"- 1. Male or female aged ≥18 years;\n- 2. Voluntarily signed written informed consent before performance of any study-related Screening procedures;\n- 3. Patients with histologically or cytologically confirmed diagnosis of advanced cancer including: a. Group A: Relapsed/refractory advanced bladder, breast, colorectal, gastric, ovarian, or prostate cancer, melanoma, or PDAC; b. Group B: Relapsed/refractory advanced hematologic malignancies including AML, acute lymphocytic leukemia, diffuse large B cell lymphoma, and follicular lymphoma; c. Group C: Relapsed/refractory advanced bladder cancer, HNSCC, melanoma, or non‑small cell lung cancer (approved indications in US and EU for pembrolizumab); d. Group D: persistent or recurrent advanced epithelial ovarian cancer, primary fallopian or primary peritoneal cancer, treated with at least 1 prior systemic platinum-containing regimen and that progressed within 6 months of the end of the most recent systemic platinum-containing regimen; e. Group E: mCRPC in patients who failed prior androgen deprivation therapy. Patients may have also failed prior taxane therapy; f.Group F: Newly diagnosed AML by WHO 2022 criteria (Khoury 2022) or MDS/AML TP53mt with 10%-19% blasts by ICC 2022 criteria (Arber 2022), in patients who are indicated to start treatment with VEN/AZA due to being aged ≥75 years, or due to being aged 18-74 years with any of the following comorbidities that preclude use of intensive induction chemotherapy. •\tCardiac history of congestive heart failure requiring treatment, left ventricular ejection fraction ≤50%, or stable chronic angina; •\tDiffusing capacity of the lung for carbon monoxide (DLCO) ≤65% or forced expiratory volume in 1 second (FEV1) ≤65%; •\tEastern Cooperative Oncology Group (ECOG) performance-status score of 2 or 3; •\tCreatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) <45 mL/min; •\tTotal bilirubin >1.5 × upper limit of normal (ULN); •\tAny other comorbidity that the physician judges to be incompatible with intensive chemotherapy should be checked by the medical monitor during Screening to approve study enrollment. Of note: Patients with antecedent aplastic anemia, MDS, or chronic myelomonocytic leukemia may be eligible if they had not received prior B cell lymphoma protein (BCL)2 inhibitors, myeloid leukemia cell differentiation protein (MCL)1 inhibitors, hypomethylating agents, chemotherapy, or allograft stem cell transplantation (SCT) for MDS. Acceptable prior therapies include erythropoietin stimulating agents, thrombopoietin receptor agonists, lenalidomide, luspatarcept, anti-thymocyte globulin, cyclosporine, and iron chelating agents. g. Group G: metastatic or unresectable melanoma with primary resistance following at least 6 weeks of prior CPI treatment for advanced disease, 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 should not have received >1 prior lines of CPI for advanced disease or have received other systemic therapy since progression on CPIs. Prior (neo)adjuvant CPI is allowed if completed ≥12 months before study treatment initiation; h. Group H: locally advanced or metastatic urothelial carcinoma in patients who are not eligible for platinum-containing chemotherapy, or who have disease progression during or following platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy; i. Group I: metastatic or unresectable, recurrent HNSCC in patients who failed first-line immunotherapy or for whom immunotherapy was contraindicated, or in patients who failed 2 prior systemic regimens including an immunotherapy.\n- 4. Willingness to undergo Screening, baseline, and on-study tumor biopsies or BMAs, as applicable;\n- 5. All groups except Group F: ECOG performance status ≤1 (see inclusion #15 for Group F); 6. Life expectancy >3 months as assessed by the Investigator 7. All groups except Group F: Clinical laboratory tests: (see inclusion #16 for Group F) Hematology: • Hemoglobin ≥8.5 g/dL (transfusion dependent or independent); • All groups except Group B and F: o platelet count ≥75 × 10 9/L; o lymphocyte count ≥0.5 × 10 9/L; o absolute neutrophil count ≥1.0 × 10 9/L. Liver enzymes: • AST and ALT ≤2.5 × ULN (<5 × ULN in the case of liver metastases); • bilirubin ≤1.5 × ULN (<2 × ULN in case of liver metastases). Renal function: serum creatinine <1.5 × ULN, or creatinine clearance CrCl or eGFR ≥50 mL/min (Cockcroft and Gault) for serum creatinine ≥1.5x ULN.\n- 8. Contraceptives measures: a. Women of childbearing potential must: i. Have a negative pregnancy test within 1 week before first dose of any study drug; ii. Use highly effective method(s) of birth control (i.e., a method with less than 1% failure rate [e.g., sterilization, hormone implants, hormone injections, some intrauterine devices, sexual abstinence, or vasectomized partner]) consistently and correctly during the study and for at least 5 months (6 months in the US) after the last dose of any study drug; iii. Agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 5 months (6 months in the US) after the last dose of any study drug; iv. Agree to no plan to breastfeed and no plan to become pregnant during the study and for at least 5 months (6 months in the US) after the last dose of any study drug. For Group F these contraceptive measures apply for 5 months (6 months in the US) after the last dose of ICT01 or for the time indicated in the prescribing information of AZA and VEN, whichever is the longest. b. Males who are sexually active must: i. Agree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 5 months (6 months in the US) after the last dose of any study drug; ii. Agree to not donate sperm during the study and for at least 5 months (6 months in the US) after the last dose of any study drug; iii. No plan to father a child during the study or within 5 months (6 months in the US) after the last dose of any study drug.\n- 9. Women must not be breastfeeding;\n- 10. At least 1 measurable lesion per RECIST/ RECIL or >5% bone marrow blasts;\n- 11. Part 1: Patients must have no available standard of care or available treatment with potential survival benefit for their disease, as determined by the treating Investigator (see inclusion criteria #13 and #14 for Groups D, E, G, H, and I and Group F, respectively). Patients with mCRPC who have a breast cancer type susceptibility protein (BRCA)1 or BRCA2 alterations mutation should have received other prior therapies including poly (ADP-ribose) polymerase (PARP) inhibitors prior to enrollment in the study unless deemed inappropriate 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 kinase (MEK) inhibitor therapy unless they have contraindications, as determined by the treating Investigator. 12. in Groups C, G, H, and I must meet the eligibility criteria in the approved package labeling of pembrolizumab and meet the following conditions: a. Must not be first-line patients (i.e., must meet Inclusion Criteria #11); b. Must not have any history of or ongoing interstitial lung disease; c. Must not have undergone prior anterior organ transplantation, including allograft SCT.\n- Part 2 Groups D, E, G, H, and I: all above criteria apply with following modifications: 13. Replaces inclusion criterion #11: Patients must have received at least one line of treatment for their cancer prior to enrolling on the study. Patients with mCRPC who have a BRCA1 or BRCA2 alterations mutation should have received other prior therapies including PARP inhibitors prior to enrollment in the study unless deemed inappropriate by the treating Investigator. Part 2 Group F: all above criteria with following modifications: 14. Replaces inclusion criterion #11: Patients must be planned to start VEN/AZA as per label indication as described in inclusion criterion 3.f; 15. Replaces inclusion criterion #5: Patient must have an ECOG Performance status of: • 0 to 2 for patients and patients aged ≥75 years; • 0 to 3 for patients aged 18-74 years. 16. Replaces inclusion criterion #7: Clinical laboratory tests a. Hematology: abnormalities should be evaluated by the Investigator as acceptable and related to the underlying disease; b. Liver enzymes: •\tAspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × ULN (<5.0 × ULN in the case of liver involvement); •\tbilirubin: o\tPatients ≥75 years of age: ≤1.5 × ULN (<2.0 × ULN in case of liver involvement); o\tPatients ≥18 to 74 years of age: total bilirubin ≤3.0 × ULN. c.\tRenal function: •\tCrCl or eGFR ≥30 mL/min."}

Exclusion criteria

• {"criterion_text":"- 1. Any malignancy of γ9δ2 T cell origin; 2. Any anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment initiation (does not apply to patients receiving pembrolizumab in the combination arms); 3. Treatment with investigational drugs within 28 days before study treatment initiation; 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-mediated adverse events (imAEs) and/or adverse events (AEs) Grade ≥2 from previous therapies, except for vitiligo, stable Grade 2 neuropathy, hair loss, and stable endocrinopathies with substitutive hormone therapy;"}
• {"criterion_text":"- 7. Within 4 weeks of major surgery; 8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy within the last 12 months; 9. Primary or secondary immune deficiency; 10. Active and uncontrolled infections requiring IV antibiotic or antiviral treatment; 11. Known/suspected hypersensitivity against ICT01, human or humanized IgGs, PD-1/PD-L1 blockers, or their excipients; 12. Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients positive for HIV can be eligible if cluster of differentiation (CD)4+ T-cell counts ≥350 cells and have no history of AIDS-defining opportunistic infections in the past 12 months, as deemed appropriate by the Investigator; 13. 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; 14. Dementia or altered mental status that would prohibit informed consent; 15. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study, as assessed by the Investigator; 16. Active drug or alcohol abuse as, as assessed by the Investigator; 17. Patients with uncontrolled and symptomatic brain metastases. Patients with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 4 weeks;"}
• {"criterion_text":"- Part 2 Group F, all above apply with following additions aligned with Viale-A trial (DiNardo et al. 2020) 18. Patients with t(15;17), t(8;21), inv(16), or t(16;16) karyotypic abnormality; 19. Patient has history of myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation; 20. Patient has a white blood cell count >25 x 10⁹/L. In the EU and UK: hydroxyurea, and/or cytarabine (up to 2 g/m2 total) is permitted to meet this criterion. In the US: hydroxyurea, leukapheresis, or cytarabine (up to2g/m2 total) is permitted to meet this criterion. 21. Patients with known symptomatic or uncontrolled central nervous system leukemia; 22. Any previous or concomitant malignancy, except when the patient has completed definitive curative-intent treatment with chemotherapy and/or surgery and/or radiotherapy at least 3 months prior to enrollment. Patients having completed definitive treatment for following conditions may be eligible immediately after completion of definitive curative intent therapy, after healing of wounds, and no evidence of residual disease by examination, imaging, and/or cytology/pathology, e.g., non-melanoma skin cancers, or a carcinoma in-situ, e.g., ductal carcinoma in situ, urothelial cancer, cervical cancer, localized prostate cancer, pre-cancerous colon polyp. 23. Patients with contraindications to VEN or AZA according to prescribing information"}

Primary endpoints

• {"endpoint_text":"- Part 1: • Incidence, severity (according to National Cancer Institute [NCI]- Common Terminology Criteria for Adverse Events [CTCAE] Version 5), and relationship to study treatment of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation of study treatment or treatment modifications; • Incidence and severity of clinical laboratory abnormalities; • Clinically significant findings on vital signs, ECGs, and physical examinations.","definition_or_measurement_approach":"Safety endpoints measured by incidence and severity graded per NCI CTCAE v5; clinical laboratory abnormalities via standard lab tests; vital signs, ECGs and physical examinations per protocol-specified timepoints."}
• {"endpoint_text":"- Part 2: • DCR according to RECIST Version 1.1 for solid tumors (complete response [CR] + partial response [PR] + stable disease [SD]); • Complete remission rate (CRR) according to the European LeukemiaNet (ELN) 2022 criteria for AML (complete remission [CR] + CR with partial hematological recovery [CRh] + CR with incomplete hematological recovery [CRi] + morphologic leukemia-free state [MLFS]).","definition_or_measurement_approach":"Efficacy assessment: Disease control rate (DCR) per RECIST v1.1 for solid tumors; Complete remission rate per ELN 2022 criteria for AML."}
• {"endpoint_text":"- Continued treatment period: DoR according to RECIST 1.1 for solid tumor or ELN 2022 criteria for AML;","definition_or_measurement_approach":"Duration of response (DoR) measured per RECIST v1.1 for solid tumors or ELN 2022 criteria for AML, using imaging and hematologic assessments as applicable."}

Secondary endpoints

• {"endpoint_text":"- Part I: Incidence of dose-limiting toxicities (DLTs), other safety measures, and biomarker data. • PK parameters of ICT01 • Presence or absence of anti-ICT01 antibodies in blood.• Disease control rate (DCR) and objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors, immunotherapy RECIST, Response Evaluation Criteria In Lymphoma, or as per disease-specific standards","definition_or_measurement_approach":"DLTs assessed per protocol-defined DLT window and CTCAE v5; PK parameters (Cmax, AUC, t½, clearance) measured from blood samples; anti-ICT01 antibodies assayed in blood; DCR/ORR assessed per RECIST/immunotherapy RECIST or disease-specific criteria."}
• {"endpoint_text":"- Part 2: •\tDifferential benefit–risk, as measured by the totality of safety, lab, PK, PD and efficacy data. •\tIncidence, severity (according to CTCAE V5), and relationship of TEAEs, SAEs and TEAEs leading to discontinuation/modification of study treatment •\tIncidence and severity (according to CTCAE V5.0) of clinical lab abnormalities; •\tCS findings on VS, ECGs, and physical exams. •\tPK parameters of ICT01, including Cmax, AUC, t½, and clearance. •\tPresence/absence of anti-ICT01 blood Ab","definition_or_measurement_approach":"Benefit–risk integrated assessment combining safety (CTCAE v5), labs, PK/PD, and efficacy endpoints; PK measured as Cmax/AUC/t½/clearance; anti-ICT01 antibodies measured in blood."}
• {"endpoint_text":"- Continued treatment period: • Presence or absence of anti-ICT01 antibodies in blood.• Incidence, severity (according to NCI CTCAE Version 5.0), and relationship to study treatment of TEAEs, SAEs, and TEAEs leading to discontinuation of study treatment or treatment modifications","definition_or_measurement_approach":"Long-term immunogenicity assessed via anti-ICT01 antibody assays; long-term safety monitored by TEAEs/SAEs graded per NCI CTCAE v5."}

Belgium

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

12-03-2025

Processing Time Days

237

Number Of Sites

1

Number Of Participants

25

France

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

05-02-2026

Processing Time Days

567

Number Of Sites

12

Number Of Participants

200

Germany

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

10-03-2025

Processing Time Days

235

Number Of Sites

1

Number Of Participants

50

Spain

Earliest CTIS Part Ii Submission Date

18-07-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

566

Number Of Sites

4

Number Of Participants

50

Primary sponsor

Full Name

Imcheck Therapeutics

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Precision for Medicine GmbH

Responsibilities

sponsorDuties codes: [4]

Name

Precision for Medicine, Oncology and Rare Disease

Responsibilities

sponsorDuties codes: [10,11,3,6,7]

Name

Eurofins Adme Bioanalyses

Responsibilities

sponsorDuties codes: [4]

Third parties

• {"country":"France","full_name":"Eurofins Adme Bioanalyses","duties_or_roles":"[4]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Precision for Medicine GmbH","duties_or_roles":"[4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Chimera Biotec GmbH","duties_or_roles":"[4]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Ilife Consulting","duties_or_roles":"[1,12,5]","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Precision for Medicine, Oncology and Rare Disease","duties_or_roles":"[10,11,3,6,7]","organisation_type":"Industry"}
• {"country":"France","full_name":"Creapharm Clinical Supplies","duties_or_roles":"[14]","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Product Life France","duties_or_roles":"[8]","organisation_type":"Pharmaceutical company"}