Save

MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer

PHASE2RECRUITING

The study is a 2-part study of Tinodasertib alone or in combination with Pembrolizumab/Irinotecan in patients with CRC.

Simpliy with AI

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.

Simplify with AI

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.

Locally determined histological diagnosis is acceptable for study entry in Module 1.

Subjects can be enrolled in module 1 regardless of microsatellite stability status.

Only subjects with CRC MSS will be enrolled in module 2, arm B'.

Subjects who have had >2 lines of prior therapy for their CRC.

Prior use of irinotecan or irinotecan containing regimens is permitted

CRC MSI-H patients should have been treated with a checkpoint inhibitor and have progressed on such therapy or found to be resistant, refractory or intolerant to the checkpoint inhibitor

Patients with an available molecularly targeted therapy such as antibodies targeting VEGF/R, EGFR, encorafenib/cetuximab, prior to study entry. Additionally, patients with driver mutations for which an FDA approved therapy is available such as BRAF V600E, HER2 or NTRK should have been offered such therapy prior to study entry.

CRC subjects will be eligible to enrol in Arm C' if they have failed an established 5-fluorouracil containing regimen and have progressed after oxaliplatin based or irinotecan-based combination therapy and do not have a driver mutation for which there is an approved targeted therapy.

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.

Simplify with AI

Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2023-04-14

Primary completion: 2024-09-30

Study completion finish: 2026-10-15

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT05462236

Intervention or treatment

DRUG: Tinodasertib

DRUG: Pembrolizumab

DRUG: Irinotecan

Conditions

• Metastatic Colorectal Cancer

Image related to Metastatic Colorectal Cancer

Condition: Metastatic Colorectal Cancer
DRUG: Tinodasertib and other drugs
Camperdown, New South Wales, Australia and more
Sponsor: AUM Biosciences Pte Ltd

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Chris O'Brien Lifehouse

Research sites nearby

Select from list below to view details:

Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Cabrini Hospital
Malvern, Victoria, Australia
Prince of Wales Hospital
Wollongong, New South Wales, Australia
Pindara Private Hospital, Gold Coast Cancer Care
Benowa, Queensland, Australia

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 Monotherapy with Tinodasertib administered orally QOD	DRUG: Tinodasertib MNK inhibitor
EXPERIMENTAL: Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan Combination doses with Tinodasertib administered orally QOD with intravenous pembrolizumab at 200mg Q3W or Irinotecan at 180mg/m2 Q2W	DRUG: Tinodasertib MNK inhibitor
EXPERIMENTAL: Module 2: Arm B' and C': Dose Expansion Combination therapy with Tinodasertib administered orally QOD at RP2D (as determined in Module 1) and either pembrolizumab at 200mg IV Q3W (arm B') or irinotecan 180mg/m2 IV Q2W (arm C')	DRUG: Tinodasertib MNK inhibitor

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome 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

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome 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

Frequently Asked Questions

Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol

No questions submitted. Be the first to ask a question!

You may be eligible to participate in this trial based on your search.Apply for study

Are you running this trial? If you're a clinic or sponsor, you can claim this study.Claim this trial

References

Clinical Trials Gov: MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer