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
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Study Summary
To evaluate ICT-01 as a single agent for the treatment of solid and hematologic malignancies.
To evaluate ICT01 (a monoclonal antibody targeting BTN3A) as monotherapy in patients with advanced solid or hematologic tumors.
To examine the combination of ICT01 plus an approved checkpoint inhibitor (CPI)
To evaluate ICT01 as monotherapy, and one CPI-approved indication receiving ICT01 plus CPI.
To assess the safety, tolerability and activity of intravenous doses of ICT01 as monotherapy and in combination with pembrolizumab, in patients with advanced-stage, relapsed/refractory cancer.
To assess ICT01 monotherapy (IV Q3W) in advanced/refractory solid and hematologic cancers.
Pharmacodynamic activity was monitored by immunophenotyping and cytokine level analysis. Tumor biopsies (baseline, Day 28) were used for immunohistochemistry of BTN3A and tumor-infiltrating lymphocytes, and gene expression profiling. Efficacy evaluations were conducted every 8 weeks.
Pharmacodynamic activity was monitored by immunophenotyping and cytokine level analysis. Tumor biopsies (baseline, Day 28) were used for immunohistochemistry of BTN3A and tumor-infiltrating lymphocytes, and gene expression profiling. Efficacy evaluations by i/RECIST 1.1 were conducted every 8 weeks.
Antitumor assessment by imaging or bone marrow analysis was done every 8 weeks after using the Response Evaluation Criteria in Lymphoma (RECIL) and IWG Criteria for AML. Safety reviews were conducted prior to dose escalation. Disease Control Rate (DCR) was the primary efficacy endpoint and defined as the sum of complete response (CR), CR with incomplete recovery (CRi), partial response (PR) and stable disease (SD). Blood samples were collected for pharmacokinetic and pharmacodynamic analyses.
To present interim results from EVICTION of ICT01 in combination with pembrolizumab in patients with checkpoint inhibitor (CPI) refractory melanoma.
In study EVICTION (NCT04243499), ICT01-pembolizumab in combination is being investigated in extensively pretreated patients with advanced-stage urothelial cell carcinoma (UCC).
Molecular baseline assessments included BTN3A tumor expression and number of γ9δ2 T cells. Patients were assessed for treatment-related adverse events (TRAE), anti-tumor efficacy (as per RECIST V1.1), and changes in γ9δ2 T cells.
To assess cytogenetics, NGS, comprehensive PD in peripheral blood (PB) and bone marrow (BM), safety, and anti-tumor efficacy.
- Voluntarily signed informed consent form.
- 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 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
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Life expectancy > 3 months as assessed by the Investigator
- At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts
- EUCTR
- Clinical labs:
- a. Hematology:
- - Hemoglobin =8.5 g/dL (equal to 5.28 mmol/L; transfusion dependent or independent);
- - Group A/C only:
- • platelet count =75 × 109/L;
- • lymphocyte count =0.5 × 109/L;
- • absolute neutrophil count =1.0 × 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) 8) Contraceptives measures:
- a.Women of childbearing potential must:
- i.have a negative pregnancy test within 1 week before first dose of study drug
- ii.use highly effective method(s) of birth control consistently and correctly during the study and for at least 5 months after the last dose of 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 after the last dose of study
- iv.agree to no plan to breastfeed and no plan to become pregnant during the study and for at least 5 months after the last dose of study drug.
- 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 after the last dose of study drug
- ii.agree to not donate sperm during the study and for at least 5 months after the last dose of study drug
- iii.no plan to father a child during the study or within 5 months after the last dose of study drug.
- Women must not be breastfeeding
- At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts
- 11) Patients must have no available standard of care for their disease, as determined by the treating Investigator
- Patients in the ICT01 Combination arms must meet the eligibility criteria in the approved package labeling of the ICI 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:
- Indication specific criteria will be provided in the protocol amendment.
- Any malignancy of V9Vd2 T cell origin
- 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)
- Treatment with investigational drug(s) 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 need for ongoing treatment.
- 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) 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.
- Within 4 weeks of major surgery
- Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy within the last 12 months
- Primary or secondary immune deficiency
- Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment
- EUCTR
- Known/suspected hypersensitivity against ICT01, human or humanized IgGs, PD-1/PD-L1 blockers or their ingredients
- Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- 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
- Dementia or altered mental status that would prohibit informed consent
- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator
- Active drug or alcohol abuse as assessed by the Investigator
- 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.
Clinical Study Information for Healthcare Providers
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