| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Relapsed/refractory solid tumors or hematological cancers |
|
| E.1.1.1 | Medical condition in easily understood language |
| Relapsed/refractory solid tumors or hematological cancers |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065147 |
| E.1.2 | Term | Malignant solid tumor |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10066481 |
| E.1.2 | Term | Hematological malignancy |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part 1
Characterize the safety and tolerability of ICT01 intravenous (IV) as
monotherapy, and in combination with pembrolizumab (Keytruda®) in
patients with relapsed/refractory advanced solid tumors or hematologic
malignancies.
Part 2
Characterize the preliminary anti-tumor activity of ICT01 IV as
monotherapy and in combination with pembrolizumab in patients with
relapsed/refractory advanced solid tumors and in combination with
venetoclax (VEN; Venclyxto®, Venclexta®)/ azacitidine (AZA; Vidaza®)
in with newly diagnosed acute myeloid leukemia (AML) |
|
| E.2.2 | Secondary objectives of the trial |
Part 1
1.Determine the recommended ICT01 dose(s) for use as monotherapy
and in combination with pembrolizumab.
2. Characterize the pharmacokinetics (PK) of IV ICT01 administered as
monotherapy and in combination with pembrolizumab
3. Characterize the preliminary anti-tumor activity of a range of IV doses
of ICT01 as monotherapy and in combination with pembrolizumab when
administered to patients with advanced-stage, relapsed/refractory solid
tumors or hematologic cancers.
Part 2
1. Determine the recommended ICT01 dose(s) for use in combination
with VEN/AZA.
2. Characterize the overall safety and tolerability of IV ICT01 as
monotherapy, and in combination with pembrolizumab or VEN/AZA
3.Characterize the PK of IV ICT01 administered as monotherapy and in
combination with pembrolizumab or VEN/AZA. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
The following criteria must be checked over the screening period and at baseline. ALL inclusion criteria must be met to include the subject in the study:
Part1 and Part2:
1) Male or female aged ≥18 years
2) Voluntarily signed written informed consent
3) Patients with histologically or cytologically confirmed diagnosis of
advanced cancer including:
a.Group A: Relapsed/refractory advanced bladder, breast, colorectal,
gastric, melanoma, ovarian, prostate and PDAC
b.Group B: Relapsed/refractory advanced hematologic malignancies
including acute myeloid leukemia, acute lymphocytic leukemia, Diffuse
large B cell lymphoma and follicular lymphoma
c.Group C: Relapsed/refractory advanced melanoma, bladder, head and
neck SCC, and non small cell lung cancer (approved indications in the US
& EU for pembrolizumab)
d.Group D: persistent or recurrent advanced epithelial ovarian cancer,
primary fallopian or primary peritoneal cancer;
e.Group E: mCRPC 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, in patients who
are indicated to start treatment with VEN/AZA
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),
h.Group H: locally advanced or metastatic urothelial carcinoma who are
not eligible for any 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.
4) Willingness to undergo Screening, baseline, and on-study tumor
biopsies or BMAs, as applicable;
5) ECOG performance status ≤ 1 (expect for Group F)
6) Life expectancy > 3 months
7)Clinical labs:
a. Hematology:
- Hemoglobin ≥8.5 g/dL
- All Groups except Group B and F:
• platelet count ≥75 × 109/L;
• lymphocyte count ≥0.5 × 109/L;
• absolute neutrophil count ≥1.0 × 109/L;
b. Liver enzymes:
- AST and 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
8) Adequate Contraceptives measures for males and women of
childbearing potential
9) Women must not be breastfeeding
10) At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts
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
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 or ongoing interstitial lung disease
c. Must not have undergone prior anterior organ transplantation,
including allograft stem cell transplantation
Part 2:
13)Replaces inclusion criterion #11 (all groups excepeted group F):
Patients must have received at least one line of treatment for their
cancer prior to enrolling on the study
14)Replaces inclusion criterion #11: Patients must be planned to start
VEN/AZA as per label indication as described in inclusion criterion 3.f;
Part 2 Group F
14)Replaces inclusion criterion #11: Patients must be planned to start
VEN/AZA as per label indication
15)Replaces inclusion criterion #5: Participant must have an ECOG
Performance status of 0 to 2 in the EU and UK
16)Replaces inclusion criterion #7: Clinical labs:
a.Hematology:
•abnormalities should be evaluated by the Investigator as acceptable
and related to the underlying disease;
•Other abnormalities should be evaluated by the investigator as
acceptable and related to the underlying disease
b.Liver enzymes:
•Aspartate transaminase (AST) and alanine transaminase (ALT) (<5 ×
ULN in the case of liver involvement);
•bilirubin:
patients ≥ 75 years of age: ≤1.5 × ULN (<2 × ULN in case of liver
involvement);
patients ≥ 18 to 74 years of age: total bilirubin ≤ 3.0 × Upper Limit of
Normal (ULN) in line with inclusion 3f.
c.Renal function (EU and UK):
•patients ≥ 75 years of age: serum creatinine <1.5 × ULN or creatinine
clearance ≥50 mL/min (Cockroft and Gault) for serum creatinine ≥1.5x
ULN
•patients ≥ 18 to 74 years of age creatinine clearance ≥ 30 mL/min in
line with inclusion in line with inclusion 3f |
|
| E.4 | Principal exclusion criteria |
The following criteria must be checked during the screening period and
at baseline. If ANY exclusion criterion applies, the subject must not be
included in the study:
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 (does
not apply to patients receiving pembrolizumab for the combination
arms)
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 lifethreatening
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) and/or AEs ≥grade 2
from previous therapies except vitiligo, stable neuropathy up to grade 2,
hair loss, and stable endocrinopathies with substitutive hormone
therapy.
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 intravenous antibiotic or
antiviral treatment
11) Known/suspected hypersensitivity against ICT01, human or
humanized IgGs, PD-1/PD-L1 blockers or their ingredients
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
assessed by the Investigator
16) Active drug or alcohol abuse as assessed by the Investigator
17) Patients with uncontrolled and symptomatic brain metastases.
Patient with asymptomatic brain metastases are allowed provided they
are stable and off therapeutic steroids for at least 4 weeks.
Group F Specific Exclusion Criteria all above apply align 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)Participant has history of myeloproliferative neoplasm (MPN)
including myelofibrosis, essential thrombocythemia, polycythemia vera,
chronic myeloid leukemia (CML) with or without BCR-ABL1 translocation
and AML with BCR-ABL1 translocation.
20) Patient has a white blood cell count >25 x 10⁹/L. In EU and
UK:Hydroxyurea, and/or cytarabine (up to 1 g total) is permitted to
meet this criterion.
21)Patients with known symptomatic or uncontrolled CNS 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, etc…
23)Patients with contraindications to VEN or AZA according to
prescribing information. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
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 (according to NCI-CTCAE Version 5) of clinical
laboratory abnormalities;
-Clinically significant findings on vital signs, electrocardiograms (ECGs),
and physical examinations.
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]).
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| On-going throughout the duration of the study |
|
| E.5.2 | Secondary end point(s) |
Part 1:
Incidence of dose-limiting toxicities (DLTs), other safety measures, and biomarker data.
PK parameters of ICT01, including maximum serum drug concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life (t1/2), clearance.
Disease control rate (DCR) and objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST), immunotherapy RECIST (iRECIST), Response Evaluation Criteria In Lymphoma (RECIL), or as per disease-specific standards in other
hematologic indications, as appropriate.
Part 2:
Incidence of DLTs, other safety measures, and biomarker data.
Incidence, severity (according to CTCAE Version 5), and relationship of TEAEs, SAEs, and TEAEs leading to discontinuation of study treatment or treatment modifications;
Incidence and severity (according to CTCAE Version 5) of clinical laboratory abnormalities;
Clinically significant findings on vital signs, ECGs, and physical examinations.
PK parameters of ICT01, including Cmax, AUC, t1/2, and clearance. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| On-going throughout the duration of the study |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 16 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| United Kingdom |
| United States |
| Belgium |
| France |
| Germany |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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