Clinical trial NCT04243499: First-in-Human Study of ICT01 in Patients With Advanced Cancer
Official title: A First-in-human, Two-part Clinical Study to Assess the Safety, Tolerability and Activity of IV Doses of ICT01 as Monotherapy and in Combination With a Checkpoint Inhibitor, in Patients With Advanced-stage, Relapsed/Refractory Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Hematopoietic/Lymphoid Cancer
Keywords: gamma delta T cells
butyrophilin
pembrolizumab
Lead sponsor: ImCheck Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-01-28
Enrollment: 292
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be assigned to a dose level of ICT01 at the time of their enrollment
Primary purpose: TREATMENT

Brief summary: Part 1 will be a dose escalation study of IV ICT01 (a monoclonal antibody targeting BTN3A) as monotherapy in patients with advanced solid or hematologic tumors, followed by a cohort examining the combination of ICT01 plus pembrolizumab (Keytruda). Part 2 will be a cohort expansion into 2 solid tumor indications and one hematologic malignancy for ICT01 monotherapy, and 3 solid tumor indications for the combination of ICT01 plus pembrolizumab.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily signed informed consent form.
2. Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer, including:

   Group A: bladder, breast, colon, gastric, melanoma, ovarian, prostate and PDAC Group B: hematologic malignancies including acute myeloid leukemia, acute lymphocytic leukemia, Diffuse large B cell lymphoma and follicular lymphoma Group C: melanoma, cervical, bladder, gastric, head and neck SCC, and lymphoma (according to the approved package labeling of the ICI) Part 2, Group D: Ovarian cancer (2L/3L) with baseline g9d2 T cells \> 20K Part 2, Group E: metastatic castrate resistant prostate cancer (2L/3L) with baseline g9d2 T cells \> 20K Part 2, Group F: newly diagnosed AML starting venetoclax/azacitidine Part 2, Group G: checkpoint-refractory metastatic melanoma with g9d2 T cells \>5K Part 2, Group H: chemotx-refractory or Pt-ineligible urotherlial cancer (bladder) with g9d2 T cells \>5K Part 2, Group I: checkpoint-refractory, metastatic HNSCC with g9d2 T cells \>5K
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 Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or \>5% marrow blasts

Exclusion Criteria:

1. Any malignancy of Vγ9Vδ2 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 ICI for the combination arm)
3. Treatment with investigational drug(s) 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 need for ongoing treatment.
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) and/or AEs ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with replacement 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

Primary outcomes:
measure: Adverse Events (Parts 1 & 2)
timeFrame: 12 months
measure: Disease Control Rate using RECIST for solid tumor patients (Part 2)
timeFrame: 12 months
measure: Disease Control Rate using RECIL for lymphoma patients (Part 2)
timeFrame: 12 months
Secondary outcomes:
measure: Change from Baseline in the Number of Circulating Gamma Delta T Cells
timeFrame: 28 days
measure: Change from Baseline in the Activation State of Circulating Gamma Delta T Cells
timeFrame: 28 days
measure: Cmax following the first dose of ICT01
timeFrame: 1 day
measure: AUC following the first dose of ICT01
timeFrame: 21 days
measure: Clearance at steady-state of ICT01
timeFrame: 6 months
measure: Half-life of ICT01
timeFrame: 6 months
measure: Objective Response Rate using RECIST for solid tumor patients (Part 2)
timeFrame: 12 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: US Oncology Research
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Haut Leveque
city: Lyon
country: France
facility: Centre Hospitalier Lyon Sud
city: Lyon
country: France
facility: Centre Lyon Berard
city: Lyon
country: France
facility: CHU Lyon
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Pitie-Salpetriere
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Gustave Roussy
city: Poitiers
country: France
facility: CHU Poitiers
city: Dresden
country: Germany
facility: University Carl Gustav Carus Clinical Trial Unit
city: Wurzburg
country: Germany
facility: universitatklinikum Wurburg
city: Barcelona
country: Spain
facility: START Barcelone HM Nou Delfos
city: Barcelona
country: Spain
facility: Vall d'Hebron Instiute of Oncology
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Institute of Cancer Research
Study officials:
affiliation: ImCheck Therapeutics
name: Katrien Lemmens, MD, PhD
role: STUDY_DIRECTOR
References: