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

NCT05462236 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: AUM001-2001-MK3475-D65KEYNOTE-D65MK-3475-D65
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• 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

  Approximately 2 years from date of participant enrolment

Secondary Outcomes (1)

• PK evaluation

  Approximately 6 months from date of participant enrolment

Study Arms (3)

Module 1: Arm A: Multiple dose finding cohorts

EXPERIMENTAL

Monotherapy with Tinodasertib administered orally QOD

Drug: Tinodasertib

Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan

EXPERIMENTAL

Combination doses with Tinodasertib administered orally QOD with intravenous pembrolizumab at 200mg Q3W or Irinotecan at 180mg/m2 Q2W

Drug: Tinodasertib; Drug: Pembrolizumab; Drug: Irinotecan

Module 2: Arm B' and C': Dose Expansion

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Irinotecan

Interventions

Tinodasertib DRUG

MNK inhibitor

Also known as: AUM001

Module 1: Arm A: Multiple dose finding cohorts; Module 2: Arm B' and C': Dose Expansion; Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan

Pembrolizumab DRUG

PD-1 Inhibitor

Also known as: KEYNOTE-D65, KEYTRUDA®

Module 2: Arm B' and C': Dose Expansion; Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan

Irinotecan DRUG

Topoisomerase inhibitor

Module 2: Arm B' and C': Dose Expansion; Module1: Arm B/C: Multiple cohorts of Tinodasertib with fixed dose of pembrolizumab or irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AUM Biosciences Pte Ltd: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (5)

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

Prince of Wales Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

Pindara Private Hospital, Gold Coast Cancer Care

Benowa, Queensland, 4217, Australia

RECRUITING

Cabrini Hospital

Malvern, Victoria, 3144, Australia

RECRUITING

Ballarat Oncology and Haematology

Wendouree, Victoria, 3355, Australia

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

pembrolizumab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

HARISH DAVE, MEDICAL

CONTACT

+1 301 275 4356; harishd@aumbiosciences.com

JOHN PATAVA, PhD

CONTACT

+61 498 071 249; johnp@aumbiosciences.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 18, 2022
• Study Start: April 14, 2023
• Primary Completion: September 30, 2024
• Study Completion (Estimated): October 15, 2026
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)