Study to Evaluate the Safety of IMM-01 in Patients With Advanced Solid Tumours

Colorectal Cancer Clinical Trial

Official title:

A Phase I Open-Label, Single-Arm, Single-Centre Study to Establish Proof of Mechanism, Pharmacokinetics (PK), Pharmacodynamics (PD), and Safety of IMM-01 as Monotherapy in Checkpoint Inhibitor Naïve Patients With Advanced Solid Tumours

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04545827
• Other study ID #: MOD-001
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2021
• Est. completion date: July 2022

Study information

• Verified date: September 2020
• Source: Modulate Therapeutics Ltd
• Contact: Study Director
• Phone: 317-651-7036
• Email: choruspharma[@]lists.lilly.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A study to assess the safety of IMM-01 in participants with advanced solid tumors

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological evidence of cancer (advanced solid tumours, excluding primary brain tumours) that is locally advanced and/or metastatic

• Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have an estimated life expectancy of greater than or equal to (=)12 weeks

• Have adequate organ function

• Renal: Estimated glomerular filtration rate (eGFR) =45 milliliters per minute (mL/min/1.73m2)

• Have discontinued cytotoxic/cytostatic therapy, and cancer-related hormonal therapy at least 21 days or a minimum of 5 half-lives prior to study enrolment (6 weeks for mitomycin-C or nitrosoureas) and have discontinued radiotherapy at least 7 days prior to the first dose of study drug if radiation field did not encompass bone marrow. Or have recovered back to baseline or Grade 1 for any therapy related Adverse Events (AE) with the exception of alopecia or Grade 1 neuropathy

• Have received at least 1 but no more than four prior systemic anti-cancer therapies for metastatic or locally advanced disease, including one immune-oncology agent

• Have adequate venous access

• Males and females with reproductive potential must agree to use medically approved contraceptives during the study and for 3 months following the last dose of study treatment

• Females of child-bearing potential must have had a negative serum or urine pregnancy test result less than or equal to (=)28 days prior to the first dose of study treatment and a negative serum or urine pregnancy test result =1 day prior to the first dose

• Tumour lesions that are considered evaluable by Response Evaluable Criteria in Solid Tumours (RECIST) Patients must be able to tolerate IV contrast for radiological evaluation

• Have discontinued any prior immune-oncology agent at least 6 weeks prior to enrollment

Additional Inclusion Criteria for Part A:

• Amenable to undergo mandatory biopsies (baseline and on treatment) at dose levels that required them based on safety observations as well as requirements for demonstration of mechanism of action

Additional Inclusion Criteria for Subset (approximately (~)50% per tumour type) of Part B:

• Amenable to undergo mandatory biopsies (baseline and on treatment)

• For Squamous Cell Carcinoma of the Head and Neck (SCCHN):

• Must have failed at least one platinum-containing regimen for metastatic disease or experienced recurrent disease within 6 months of completing a platinum-containing regimen

• For Squamous Cell Carcinoma (SCC) of the oesophagus:

• Must have failed at least one platinum-containing regimen for metastatic disease or experienced recurrent disease within 6 months of completing a platinum-containing regimen

• For metastatic Uveal Melanoma (UM):

• May have failed up to four local liver therapies such as trans arterial chemoembolization (TACE)

• May have failed up to two prior systemic therapies for metastatic disease

• For Renal Cell Carcinoma (RCC):

• May have failed up to four prior systemic therapies for metastatic or locally advanced disease including 1 immunotherapy agent

• For Colorectal Cancer with mismatch-repair (MMR) deficiency

• Must have failed at least one chemotherapy regimen for metastatic disease or experienced recurrent disease within 6 months

• May have failed an anti-angiogenesis agent

• May have failed an anti-epidermal growth factor receptor (EGFR) agent

• May have failed one immunotherapy agent

Exclusion Criteria:

• Symptomatic central nervous system (CNS) metastasis. Patients with treated Central Nervous System (CNS) metastases are eligible, provided their disease is stable for minimum of 4 weeks, asymptomatic, and they are not currently receiving corticosteroids

• Grade 2 or greater peripheral neuropathy

• History of organ transplant (e.g., heart, lungs, liver, and kidney)

• Females who are pregnant or nursing

• Allogeneic bone marrow transplant

• Prior Interleukin-2 (IL-2) treatment or known hypersensitivity to IL-2

• Patients with a history of active acquired immune deficiency syndrome (AIDS), who are known to be antigen positive Hepatitis B, or Hepatitis C

• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, myocardial infarction (MI) or stroke within the past 6 months. Symptomatic bradycardia or other symptomatic conduction abnormities. Unstable angina.

• Any medical condition which places the patient at unacceptable risk

Related Conditions & MeSH terms

• Advanced Cancer
• Carcinoma
• Carcinoma, Renal Cell
• Colorectal Cancer
• Colorectal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Neoplasms
• Renal Cell Carcinoma
• Solid Carcinoma
• Solid Tumor
• Squamous Cell Car. - Esophagus
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck
• Uveal Melanoma

Intervention

Drug:
• IMM-01
Once weekly

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Modulate Therapeutics Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Maximum Tolerated Dose	Maximum tolerated dose as monotherapy	Baseline up to approximately 28 days (Cycle 1)
Primary	Part B: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) or Any Serious Adverse Events (SAEs)	Medical occurrences that emerge during treatment and were either absent pretreatment or have worsened relative to the pretreatment state	Baseline up to approximately 3 years
Secondary	Part A: Area under the concentration versus time curve during a dosing interval (AUC0-t) of losartan and its active metabolite (EXP3174)	Area under the concentration versus time curve during a dosing interval	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Area under the concentration versus time curve during a dosing interval (AUC0-t) of losartan and its active metabolite (EXP3174)	Area under the concentration versus time curve during a dosing interval	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Area under the concentration time curve from time zero to 24 hours post dose (AUC0-24) of losartan and its active metabolite (EXP3174)	Area under the concentration time curve from time zero to 24 hours	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Area under the concentration time curve from time zero to 24 hours post dose (AUC0-24) of losartan and its active metabolite (EXP3174)	Area under the concentration time curve from time zero to 24 hours	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Observed maximum plasma concentration (Cmax) of losartan and its active metabolite (EXP3174)	Following administration of IMM-01	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Observed maximum plasma concentration (Cmax) of losartan and its active metabolite (EXP3174)	Observed maximum plasma concentration	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Time to Cmax (tmax) of losartan and its active metabolite (EXP3174)	Time to Cmax	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Time to Cmax (tmax) of losartan and its active metabolite (EXP3174)	Time to Cmax	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Apparent clearance of losartan and its active metabolite (EXP3174)	Apparent clearance	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Apparent clearance of losartan and its active metabolite (EXP3174)	Apparent clearance	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Volume of distribution of losartan and its active metabolite (EXP3174)	Volume of distribution	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Volume of distribution of losartan and its active metabolite (EXP3174)	Volume of distribution	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part A: Elimination half-life (t1/2) of losartan and its active metabolite (EXP3174)	Elimination half-life	Baseline up to approximately 28 days (Cycle 1)
Secondary	Part B: Elimination half-life (t1/2) of losartan and its active metabolite (EXP3174)	Elimination half-life	Baseline up to approximately 28 days (Cycle 1)