MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer
The study is a 2-part study of Tinodasertib alone or in combination with Pembrolizumab/Irinotecan in patients with CRC.
Study details:
The study is conducted in 2 parts. First a dose escalation Run-in to identify the Maximum Tolerable Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of Tinodasertib to be administered orally as monotherapy and in combination with intravenous pembrolizumab/irinotecan. Part 2 consists of a cohort expansion at the RP2D of Tinodasertib n combination with intravenous pembrolizumab/Irinotecan in patients with locally advanced or metastatic CRC to evaluate clinical activity and safety of Tinodasertib.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- The participant provides written informed consent for the trial.
- Subjects are at least 18 years of age at the time of signing the Informed Consent Form.
- Subjects with histologically or cytologically confirmed diagnosis of locally advanced or metastatic CRC.
- Subjects who have had >2 lines of prior therapy for their CRC.
- Subject must have provided archival tumor tissue sample or newly obtained core or excisional or punch needle biopsy of a tumor lesion not previously irradiated.
- Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiologist.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Have a predicted life expectancy of greater or equal to 3 months.
- Have adequate organ function.
- HIV infected participants must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease.
- Women of childbearing potential must not be breastfeeding and must have a negative serum or urine pregnancy test. Must be willing to use an adequate method of contraception.
- Women of non-childbearing potential: Evidence of post-menopausal status is required.
- Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide. Male subjects should refrain from sperm donation throughout this period.
Exclusion criteria
- Has a history of another malignancy within 2 years prior to first investigational product administration, unless the malignancy was treated with curative intent and the likelihood of relapse is <5% in 2 years.
- Has known active CNS metastases and/or carcinomatous meningitis.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whichever is shorter prior to study treatment.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has had an allogeneic tissue/solid organ transplant.
- Pregnant or breastfeeding.
- Has a known history or Hepatitis B (defined as HbsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Gastrointestinal (GI) tract disease causing the inability to take oral medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor, and was discontinued from that treatment due to a Grade 3 or higher irAE.
- Participants must have recovered from all radiation-related toxicities, not require corticosteroids, or have had history of radiation pneumonitis.
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE2
Study ID
NCT05462236
Intervention or treatment
DRUG: Tinodasertib
DRUG: Pembrolizumab
DRUG: Irinotecan
Conditions
- Metastatic Colorectal Cancer
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Research sites nearby
Closest Location:
Chris O'Brien Lifehouse
Select from list below to view details:
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Prince of Wales Hospital
Wollongong, New South Wales, Australia
Pindara Private Hospital, Gold Coast Cancer Care
Benowa, Queensland, Australia
Cabrini Hospital
Malvern, Victoria, Australia
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Who is running the clinical trial?
AUM Biosciences Pte Ltd
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Module 1: Arm A: Multiple dose finding cohorts
| Drug: Tinodasertib |
EXPERIMENTAL: Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan
| Drug: Tinodasertib, Drug: Pembrolizumab, Drug: Irinotecan |
EXPERIMENTAL: Module 2: Arm B' and C': Dose Expansion
| Drug: Tinodasertib, Drug: Pembrolizumab, Drug: Irinotecan |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events and Serious Adverse events | Incidence and severity of AEs and SAEs. | Approximately 2 years from date of participant enrolment |
| Incidence of DLT events and treatment emergent AEs (TEAEs) | Grading of DLTs according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 | 1 complete cycle (21 days) |
| Objective response rate based on Response Evaluation Criteria in Solid tumors (RECIST) Version 1.1 | Not Specified | Approximately 2 years from date of participant enrolment |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| PK evaluation | Evaluation of Plasma concentrations of AUM001 as monotherapy or in combination with Pembrolizumab/Irinotecan | Approximately 6 months from date of participant enrolment |
References
Clinical Trials Gov: MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal CancerOther trials to consider
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