Trial of INI-4001 in Patients With Advanced Solid Tumours

Inimmune

Status and phase

Enrolling

Phase 1

Conditions

Advanced Solid Tumor

Treatments

Combination Product: Cemiplimab

Combination Product: Pembrolizumab

Drug: INI-4001

Combination Product: Durvalumab

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Study type

Interventional

Funder types

Industry

Identifiers

NCT06302426

INI-4001-101

Details and patient eligibility

About

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.

Full 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.

Enrollment

50 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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:
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.
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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

50 participants in 6 patient groups

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 1

Experimental group

Description:

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.

Treatment:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 2

Experimental group

Description:

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.

Treatment:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 3

Experimental group

Description:

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.

Treatment:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 4

Experimental group

Description:

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.

Treatment:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 5

Experimental group

Description:

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.

Treatment:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab

INI-4001 Monotherapy Dose Escalation - INI-4001 Dose Level 6

Experimental group

Description:

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:

Combination Product: Atezolizumab

Combination Product: Avelumab

Combination Product: Nivolumab

Combination Product: Durvalumab

Drug: INI-4001

Combination Product: Pembrolizumab

Combination Product: Cemiplimab