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

Overview

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.

Interventions

• Drug INI-4001
  INI-4001 is a small molecule TLR7/8 agonist being developed as a standalone treatment for the induction of anti-tumour immune responses and sensitization to immune checkpoint inhibitor (ICI) therapy.
• Combination product Nivolumab
  During both Phase Ia and Phase Ib, patients may meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) may transition to combination therapy.
• Combination product Pembrolizumab
  During both Phase Ia and Phase Ib, patients meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) transition to combination therapy.
• Combination product Cemiplimab
  During both Phase Ia and Phase Ib, patients meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) transition to combination therapy.
• Combination product Avelumab
  During both Phase Ia and Phase Ib, patients meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) transition to combination therapy.
• Combination product Atezolizumab
  During both Phase Ia and Phase Ib, patients meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) transition to combination therapy.
• Combination product Durvalumab
  During both Phase Ia and Phase Ib, patients meeting required criteria (at the discretion of the PI in consultation with the study Sponsor) transition to combination therapy.

Primary outcome measures

• Incidence of dose-limiting toxicities (DLTs) during Cycle 1 to determine the maximum tolerated dose of INI-4001 Monotherapy [Time frame: Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21]

Secondary outcome measures (12)

• Incidence, type, and severity of treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment after multiple ascending doses [Time frame: Assessed at Screening, then daily from Cycle 1 Day 1 through to 30 days post last dose of INI-4001]
• Incidence and nature of dose-limiting toxicities (DLTs) and regimen-limiting toxicities (RLTs) leading to discontinuation of study treatment after multiple ascending doses [Time frame: Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21]
• Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses [Time frame: Assessed at Screening, then Cycle 1 Day 1 through to 30 days post last dose of INI-4001]
• Number of Participants with a Change from baseline in body weight after multiple ascending doses [Time frame: 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]
• Number of Participants with a Change from baseline in clinical laboratory parameters (haematology) after multiple ascending doses [Time frame: 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]
• Number of Participants with a Change from baseline in clinical laboratory parameters (serum chemistry) after multiple ascending doses [Time frame: 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]
• Number of Participants with a Change from baseline in clinical laboratory parameters (urinalysis) after multiple ascending doses [Time frame: 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]
• Change from baseline in measurements of HR in beats per minute after multiple ascending doses [Time frame: 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]
• Change from baseline in measurements of PR interval via 12-lead electrocardiogram after multiple ascending doses [Time frame: 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]
• Change from baseline in measurements of QT interval via 12-lead electrocardiogram after multiple ascending doses [Time frame: 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]
• Change from baseline in measurements of RR interval in breaths per minute via 12-lead electrocardiogram after multiple ascending doses [Time frame: 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]
• Change from baseline in measurements of QRS duration via 12-lead electrocardiogram after multiple ascending doses [Time frame: 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]

Eligibility criteria

Inclusion criteria

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

• 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)
• Patient is neurologically stable and has had no persistent side effects / complications from prior treatment.
• 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.
• 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

• Prior therapy with a TLR7 and/or TLR8 agonist, unless first approved by the medical monitor.
• Has primary brain/CNS tumour or untreated spinal cord compression.
• Has known active, uncontrolled brain or CNS metastases and/or carcinomatous meningitis.
• Evidence of abnormal cardiac function
• 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.
• 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.
• History of other malignancy not meeting inclusion criterion #1 within the past 2 years
• Major surgery within 28 days of Cycle 1, Day 1, or minor surgical procedures within 7 days of Cycle 1, Day 1.
• Received cancer-directed therapy
• A history of autoimmune diseases that has caused terminal organ damage or required systemic immunosuppression / systemic disease modulating drugs within the past 2 years.
• 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.
• History of prior organ allograft.
• Known hypersensitivity to the study drug or its inactive ingredients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 3 centers

• The Border Cancer Hospital — Albury
• Southern Oncology Clinical Research Unit — Bedford Park
• Cabrini Hospital — Malvern

Identifiers

NCT: NCT06302426 · INI-4001-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗