Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06302426




Registration number
NCT06302426
Ethics application status
Date submitted
16/01/2024
Date registered
8/03/2024
Date last updated
8/03/2024

Titles & IDs
Public title
Trial of INI-4001 in Patients With Advanced Solid Tumours
Scientific title
An Open-label, Multiple-Ascending Dose, Two-Part Dose Ranging and Cohort Expansion Study of INI-4001 in Patients With Advanced Solid Tumours
Secondary ID [1] 0 0
INI-4001-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumor 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - INI-4001
Combination Product - Nivolumab
Combination Product - Pembrolizumab
Combination Product - Cemiplimab
Combination Product - Avelumab
Combination Product - Atezolizumab
Combination Product - Durvalumab

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 1 - 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.

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 2 - 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.

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 3 - 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.

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 4 - 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.

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 5 - 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.

Experimental: INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 6 - 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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of dose-limiting toxicities (DLTs) during Cycle 1 to determine the maximum tolerated dose of INI-4001 Monotherapy
Timepoint [1] 0 0
Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21
Secondary outcome [1] 0 0
Incidence, type, and severity of treatment-emergent adverse events (TEAEs) leading to discontinuation of study treatment after multiple ascending doses
Timepoint [1] 0 0
Assessed at Screening, then daily from Cycle 1 Day 1 through to 30 days post last dose of INI-4001
Secondary outcome [2] 0 0
Incidence and nature of dose-limiting toxicities (DLTs) and regimen-limiting toxicities (RLTs) leading to discontinuation of study treatment after multiple ascending doses
Timepoint [2] 0 0
Assessed from Cycle 1 Day 1 through to Cycle 1 Day 21
Secondary outcome [3] 0 0
Number of Participants with a Change from baseline in Vital signs measurements after multiple ascending doses
Timepoint [3] 0 0
Assessed at Screening, then Cycle 1 Day 1 through to 30 days post last dose of INI-4001
Secondary outcome [4] 0 0
Number of Participants with a Change from baseline in body weight after multiple ascending doses
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Number of Participants with a Change from baseline in clinical laboratory parameters (haematology) after multiple ascending doses
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Number of Participants with a Change from baseline in clinical laboratory parameters (serum chemistry) after multiple ascending doses
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Number of Participants with a Change from baseline in clinical laboratory parameters (urinalysis) after multiple ascending doses
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Change from baseline in measurements of HR in beats per minute after multiple ascending doses
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Change from baseline in measurements of PR interval via 12-lead electrocardiogram after multiple ascending doses
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Change from baseline in measurements of QT interval via 12-lead electrocardiogram after multiple ascending doses
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Change from baseline in measurements of RR interval in breaths per minute via 12-lead electrocardiogram after multiple ascending doses
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Change from baseline in measurements of QRS duration via 12-lead electrocardiogram after multiple ascending doses
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Change from baseline in measurements of QTcF via 12-lead electrocardiogram after multiple ascending doses
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
Change from baseline in Eastern Cooperative Oncology Group (ECOG) score after multiple ascending doses
Timepoint [14] 0 0
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
Secondary outcome [15] 0 0
Single dose PK Parameters - maximum observed concentration (Cmax)
Timepoint [15] 0 0
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)
Secondary outcome [16] 0 0
Multiple dose PK Parameters - maximum observed concentration (Cmax)
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Single dose PK Parameters - Time to Cmax (Tmax)
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Multiple dose PK Parameters - Time to Cmax (Tmax)
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Single dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Single dose PK Parameters - Total amount excreted in urine (Ae)
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
Single dose PK Parameters - Fraction excreted in the urine (Fe)
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
Single dose PK Parameters - Renal clearance (CLr)
Timepoint [22] 0 0
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)
Secondary outcome [23] 0 0
Multiple dose PK Parameters - Area under the concentration-time curve from time 0 to 24 hours post-dose (AUC0-24)
Timepoint [23] 0 0
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)
Secondary outcome [24] 0 0
Single dose PK Parameters - Area under the concentration-time curve (AUC0-t)
Timepoint [24] 0 0
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)
Secondary outcome [25] 0 0
Multiple dose PK Parameters - Area under the concentration-time curve (AUC0-t)
Timepoint [25] 0 0
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)
Secondary outcome [26] 0 0
Single dose PK Parameters - Half-life (t1/2)
Timepoint [26] 0 0
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)
Secondary outcome [27] 0 0
Multiple dose PK Parameters - Half-life (t1/2)
Timepoint [27] 0 0
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)
Secondary outcome [28] 0 0
Single dose PK Parameters - Clearance (Cl)
Timepoint [28] 0 0
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)
Secondary outcome [29] 0 0
Multiple dose PK Parameters - Clearance (Cl)
Timepoint [29] 0 0
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)
Secondary outcome [30] 0 0
Single dose PK Parameters - Volume of distribution (Vz)
Timepoint [30] 0 0
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)
Secondary outcome [31] 0 0
Multiple dose PK Parameters - Volume of distribution (Vz)
Timepoint [31] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
29/03/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/04/2026
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Border Cancer Hospital - Albury
Recruitment hospital [2] 0 0
Cabrini Hospital - Malvern
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
3144 - Malvern

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Inimmune Corporation
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Avance Clinical Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06302426
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jon L Ruckle
Address 0 0
Inimmune Corp
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Paul Wabnitz, Dr
Address 0 0
Country 0 0
Phone 0 0
+61 448665638
Fax 0 0
Email 0 0
paul.wabnitz@clinpharma.com.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06302426