Clinical trial NCT06302426: Trial of INI-4001 in Patients With Advanced Solid Tumours
Official title: An Open-label, Multiple-Ascending Dose, Two-Part Dose Ranging and Cohort Expansion Study of INI-4001 in Patients With Advanced Solid Tumours
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Inimmune Corporation
Sponsor class: INDUSTRY
Collaborators: name: Avance Clinical Pty Ltd.
First posted: 2024-03-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a Phase Ia/Ib, open-label, dose-escalation and dose expansion study. This study will be conducted in two parts: Phase Ia (dose escalation) and Phase Ib (dose expansion).
Primary purpose: TREATMENT

Brief summary: Phase 1 open-label, dose-escalation and dose-expansion study of INI-4001 as a single agent and in combination with approved checkpoint inhibitors in subjects with advanced solid tumors.

Detailed description: This is a Phase Ia/Ib, open-label, dose-escalation, and dose expansion study. This study will be conducted in two parts: Phase Ia (dose escalation) and Phase Ib (dose expansion). Phase Ia will initially seek to establish the MTD of INI-4001 administered as a monotherapy. Following identification of the MTD, any dose level at or below the MTD may be further expanded to further explore the safety, PK, PD, and preliminary efficacy of INI-4001 alone and in combination with a complementary therapy (Phase Ib).

Following cessation of INI-4001, patients will be requested to participate in long-term follow-up to assess overall survival. This long-term follow-up will continue for each patient until at least 1 year after their last dose of INI-4001, or until otherwise advised by the Sponsor.

Eligibility criteria: Inclusion Criteria:

1. Patient has locally advanced or metastatic cancer (all solid tumours allowed except primary brain/CNS tumour or untreated spinal cord compression)
2. Patient has at least one extracranial measurable disease lesion per RECIST 1.1/ iRECIST criteria.
3. Patients with known brain metastases are eligible if they meet all the following criteria:

   1. Patient has received definitive treatment of brain metastases with stereotactic body radiation therapy (SBRT) or surgery provided that the brain lesions are stable (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment)
   2. Patient is neurologically stable and has had no persistent side effects / complications from prior treatment.
   3. Patient has no evidence of new or enlarging brain metastases (confirmed by repeat imaging) and has not required steroids for at least 14 days prior to first dose administration on Day 1.
4. Female patients must be of non-child-bearing potential i.e., surgically sterilised at least 6 weeks before the screening visit or postmenopausal

Exclusion Criteria:

1. Prior therapy with a TLR7 and/or TLR8 agonist, unless first approved by the medical monitor.
2. Has primary brain/CNS tumour or untreated spinal cord compression.
3. Has known active, uncontrolled brain or CNS metastases and/or carcinomatous meningitis.
4. Evidence of abnormal cardiac function
5. Clinically significant active infection within 2 weeks prior to commencement of treatment, or unexplained fever (temperature \> 38.1°C) within 7 days prior to first dose administration on Cycle 1 Day 1.
6. Known active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
7. History of other malignancy not meeting inclusion criterion #1 within the past 2 years
8. Major surgery within 28 days of Cycle 1, Day 1, or minor surgical procedures within 7 days of Cycle 1, Day 1.
9. Received cancer-directed therapy
10. A history of autoimmune diseases that has caused terminal organ damage or required systemic immunosuppression / systemic disease modulating drugs within the past 2 years.
11. Chronic use of immune-suppressive drugs (i.e., systemic corticosteroids used in the management of cancer or non-cancer related illnesses, (e.g., COPD) in dosing exceeding 10 mg daily of prednisone equivalent). Inhaled steroids are allowed.
12. History of prior organ allograft.
13. Known hypersensitivity to the study drug or its inactive ingredients.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) during Cycle 1 to determine the maximum tolerated dose of INI-4001 Monotherapy
timeFrame: Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21
Secondary outcomes:
measure: Incidence, type, and severity of treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment after multiple ascending doses
timeFrame: Assessed at Screening, then daily from Cycle 1 Day 1 through to 30 days post last dose of INI-4001
measure: Incidence and nature of dose-limiting toxicities (DLTs) and regimen-limiting toxicities (RLTs) leading to discontinuation of study treatment after multiple ascending doses
timeFrame: Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21
measure: Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to 30 days post last dose of INI-4001
measure: Number of Participants with a Change from baseline in body weight after multiple ascending doses
timeFrame: Assessed at Screening then pre-dose on Day 1 of each 21 day cycle, assessed for up to 36 months or until disease progression, which occurs first
measure: Number of Participants with a Change from baseline in clinical laboratory parameters (haematology) after multiple ascending doses
timeFrame: Assessed at Screening, then Day 1 and Day 15 of each 21 day cycle, assessed for up to 36 months or until disease progression, which occurs first
measure: Number of Participants with a Change from baseline in clinical laboratory parameters (serum chemistry) after multiple ascending doses
timeFrame: Assessed at Screening, then Day 1 and Day 15 of each 21 day cycle, assessed for up to 36 months or until disease progression, which occurs first
measure: Number of Participants with a Change from baseline in clinical laboratory parameters (urinalysis) after multiple ascending doses
timeFrame: Assessed at Screening, then Day 1 and Day 15 of each 21 day cycle, assessed for up to 36 months or until disease progression, which occurs first
measure: Change from baseline in measurements of HR in beats per minute after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in measurements of PR interval via 12-lead electrocardiogram after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in measurements of QT interval via 12-lead electrocardiogram after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in measurements of RR interval in breaths per minute via 12-lead electrocardiogram after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in measurements of QRS duration via 12-lead electrocardiogram after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in measurements of QTcF via 12-lead electrocardiogram after multiple ascending doses
timeFrame: Assessed at Screening, then Cycle 1 Day 1 through to Day 16 and then at 7 days and 30 days post last dose of INI-4001
measure: Change from baseline in Eastern Cooperative Oncology Group (ECOG) score after multiple ascending doses
timeFrame: Screening, then Cycle 1 & Cycle 2 (each cycle is 21 days) on Day 1, Day 8 and Day 15 and then at 7 days and 30 days post last dose of INI-4001
measure: Single dose PK Parameters - maximum observed concentration (Cmax)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - maximum observed concentration (Cmax)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Time to Cmax (Tmax)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - Time to Cmax (Tmax)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Total amount excreted in urine (Ae)
timeFrame: Cycle 1 Day 1 pre-dose, then 0-2, 2-4 and 4-6 hours post-dose, Day 1 to Day 2 6-24 hours post-dose (each cycle is 21 days)
measure: Single dose PK Parameters - Fraction excreted in the urine (Fe)
timeFrame: Cycle 1 Day 1 pre-dose, then 0-2, 2-4 and 4-6 hours post-dose, Day 1 to Day 2 6-24 hours post-dose (each cycle is 21 days)
measure: Single dose PK Parameters - Renal clearance (CLr)
timeFrame: Cycle 1 Day 1 pre-dose, then 0-2, 2-4 and 4-6 hours post-dose, Day 1 to Day 2 6-24 hours post-dose (each cycle is 21 days)
measure: Multiple dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Area under the concentration-time curve (AUC0-t)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - Area under the concentration-time curve (AUC0-t)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Half-life (t1/2)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - Half-life (t1/2)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Clearance (Cl)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - Clearance (Cl)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Single dose PK Parameters - Volume of distribution (Vz)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
measure: Multiple dose PK Parameters - Volume of distribution (Vz)
timeFrame: Cycle 1 Day 1 & Day 15, pre-dose, EOI (within 2 minutes), then 15 & 30 minutes, 1, 2, 4 & 6 hours post-dose, Day 2 & Day 16 at 24 hours post-dose, Cycle 2 & 4 Day 1 pre-dose, EOI, Day 8 pre-dose then 7 days post last infusion (a cycle is 21 days)
Other outcomes:
Locations:
city: Albury
country: Australia
facility: The Border Cancer Hospital
state: New South Wales
city: Malvern
country: Australia
facility: Cabrini Hospital
state: Victoria
Study officials:
affiliation: Inimmune Corp
name: Jon L Ruckle
role: STUDY_DIRECTOR
References: