Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05462236




Registration number
NCT05462236
Ethics application status
Date submitted
7/07/2022
Date registered
18/07/2022
Date last updated
28/02/2024

Titles & IDs
Public title
MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer
Scientific title
A Phase II Open Label, Dose-finding run-in and Cohort Expansion Study to Evaluate the Safety, Tolerability and Effectiveness of Tinodasertib in Combination With Pembrolizumab or Irinotecan in Metastatic Colorectal Cancer
Secondary ID [1] 0 0
KEYNOTE-D65
Secondary ID [2] 0 0
AUM001-2001-MK3475-D65
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tinodasertib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Irinotecan

Experimental: Module 1: Arm A: Multiple dose finding cohorts - Monotherapy with Tinodasertib administered orally QOD

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 350mg/m2 Q3W

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 350mg/m2 IV Q3W (arm C')


Treatment: Drugs: Tinodasertib
MNK inhibitor

Treatment: Drugs: Pembrolizumab
PD-1 Inhibitor

Treatment: Drugs: Irinotecan
Topoisomerase inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse events and Serious Adverse events
Timepoint [1] 0 0
Approximately 2 years from date of participant enrolment
Primary outcome [2] 0 0
Incidence of DLT events and treatment emergent AEs (TEAEs)
Timepoint [2] 0 0
1 complete cycle (21 days)
Primary outcome [3] 0 0
Objective response rate based on Response Evaluation Criteria in Solid tumors (RECIST) Version 1.1
Timepoint [3] 0 0
Approximately 2 years from date of participant enrolment
Secondary outcome [1] 0 0
PK evaluation
Timepoint [1] 0 0
Approximately 6 months from date of participant enrolment

Eligibility
Key inclusion criteria
Main Inclusion criteria:

1. The participant provides written informed consent for the trial.

2. Subjects are at least 18 years of age at the time of signing the Informed Consent Form

3. Subjects with histologically or cytologically confirmed diagnosis of locally advanced
or metastatic CRC.

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

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

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

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

1. Prior use of irinotecan or irinotecan containing regimens is permitted

2. 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

3. 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.

4. 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.

5. 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.

6. Have measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiologist.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

8. Have a predicted life expectancy of greater or equal to 3 months.

9. Have adequate organ function

10. HIV infected participants must be on anti-retroviral therapy (ART) and have a
well-controlled HIV infection/disease

11. 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.

12. Women of non-childbearing potential: Evidence of post-menopausal status is required.

13. 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.

Main
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. 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.

2. Has known active CNS metastases and/or carcinomatous meningitis.

3. Has received prior systemic anti-cancer therapy including investigational agents
within 4 weeks or 5 half-lives, whichever is shorter prior to study treatment.

4. 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.

5. Has had an allogeneic tissue/solid organ transplant.

6. Pregnant or breastfeeding

7. 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.

8. 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.

9. Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.

10. Gastrointestinal (GI) tract disease causing the inability to take oral medication.

11. 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.

12. Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, or have had history of radiation pneumonitis.

13. Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/04/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/10/2026
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Wollongong
Recruitment hospital [3] 0 0
Pindara Private Hospital, Gold Coast Cancer Care - Benowa
Recruitment hospital [4] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [5] 0 0
Ballarat Oncology and Haematology - Wendouree
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
4217 - Benowa
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
3355 - Wendouree

Funding & Sponsors
Primary sponsor type
Other
Name
AUM Biosciences Pte Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The study is a 2-part study of Tinodasertib alone on in combination with
Pembrolizumab/Irinotecan in patients with CRC.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05462236
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
HARISH DAVE, MEDICAL
Address 0 0
Country 0 0
Phone 0 0
+1 301 275 4356
Fax 0 0
Email 0 0
harishd@aumbiosciences.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05462236