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| Name | Class |
|---|---|
| Avance Clinical Pty Ltd. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 1 | Experimental | For dose-level 1, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 2 | Experimental | For dose-level 2, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 3 | Experimental | For dose-level 3, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| INI-4001 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs) during Cycle 1 to determine the maximum tolerated dose of INI-4001 Monotherapy | Graded using a 5 point scale | Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence, type, and severity of treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment after multiple ascending doses | Graded using a 5 point scale | 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 |
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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:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Paul Wabnitz, Dr | Contact | +61 448665638 | paul.wabnitz@clinpharma.com.au | |
| Lucinda Tennant | Contact | +1 406 451 5913 | Lucinda.Tennant@inimmune.com |
| Name | Affiliation | Role |
|---|---|---|
| Jon L Ruckle | Inimmune Corp | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Border Cancer Hospital | Recruiting | Albury | New South Wales | 2640 | Australia |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| C582435 | pembrolizumab |
| C000627974 | cemiplimab |
| C000609138 | avelumab |
| C000594389 | atezolizumab |
| C000613593 | durvalumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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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).
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| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 4 |
| Experimental |
For dose-level 4, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 5 | Experimental | For dose-level 5, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 6 | Experimental | For dose-level 6, INI-4001 will be administered intravenously once per week on Days 1, 8 and 15 of a 21-day cycle. A complementary therapy may be introduced in combination with INI-4001. |
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| Nivolumab | Combination Product | 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. |
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| Pembrolizumab | Combination Product | 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. |
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| Cemiplimab | Combination Product | 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. |
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| Avelumab | Combination Product | 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. |
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| Atezolizumab | Combination Product | 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. |
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| Durvalumab | Combination Product | 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. |
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Graded using a 5 point scale |
| 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 | Pulse rate [PR], systolic and diastolic blood pressure [BP], temperature, respiratory rate.[RR] and oxygen saturation. Blood pressure will be measured using a sphygmomanometer, body temperature will be measured using a thermometer, Heart rate (HR) is measured using vital sign machine,respiratory rate is measured manually via 60- second count.[RR] and oxygen saturation is measured using a Oximeter. All abnormal assessments measured as Clinically significant post dose will be recorded as AEs. | 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 | Weight will be measured utilising scales | 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 | Haematology - blood samples will be collected. All safety laboratory assessments will be assessed by a local laboratory according to their reference ranges. | 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 | Serum Chemistry - blood samples will be collected. All safety laboratory assessments will be assessed by a local laboratory according to their reference ranges. | 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 | Urinalysis - urine samples will be collected. All safety laboratory assessments will be assessed by a local laboratory according to their reference ranges. | 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 | 12-lead ECG parameters include the measurements of HR in beats per minute. 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 | 12-lead ECG parameters include the measurements of PR interval. 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 | 12-lead ECG parameters include the . 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 | 12-lead ECG parameters include the measurements of RR interval in breaths per minute. 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 | 12-lead ECG parameters include the measurements of QRS duration. 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 QTcF via 12-lead electrocardiogram after multiple ascending doses | 12-lead ECG parameters include the measurements of QTcF. 12-lead ECG will be taken in triplicate at screening and prior to infusion and as single measurements at all other timepoints. | 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 Eastern Cooperative Oncology Group (ECOG) score after multiple ascending doses | Graded using a 6 point scale | 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 |
| Single dose PK Parameters - maximum observed concentration (Cmax) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - maximum observed concentration (Cmax) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Time to Cmax (Tmax) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - Time to Cmax (Tmax) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Single dose PK Parameters - Total amount excreted in urine (Ae) | Pharmacokinetics (PK) of INI-4001 in urine following a single dose | 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) |
| Single dose PK Parameters - Fraction excreted in the urine (Fe) | Pharmacokinetics (PK) of INI-4001 in urine following a single dose | 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) |
| Single dose PK Parameters - Renal clearance (CLr) | Pharmacokinetics (PK) of INI-4001 in urine following a single dose | 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) |
| Multiple dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Area under the concentration-time curve (AUC0-t) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - Area under the concentration-time curve (AUC0-t) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Half-life (t1/2) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - Half-life (t1/2) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Clearance (Cl) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - Clearance (Cl) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Single dose PK Parameters - Volume of distribution (Vz) | Pharmacokinetics (PK) of INI-4001 in blood plasma following a single dose | 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) |
| Multiple dose PK Parameters - Volume of distribution (Vz) | Pharmacokinetics (PK) of INI-4001 in blood plasma following multiple doses | 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) |
| Southern Oncology Clinical Research Unit | Recruiting | Bedford Park | South Australia | 5042 | Australia |
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| Cabrini Hospital | Recruiting | Malvern | Victoria | 3144 | Australia |
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| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |