Clinical trial of MK-4280A for colorectal cancer that has spread after previous treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Nov 2021 → 22 Feb 2025

Decision date (initial)

2024-05-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2024-511043-25-00

EudraCT number

2021-001309-60

WHO UTN

U1111-1302-9933

ClinicalTrials.gov

NCT05064059

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Pharmacogenomic, Pharmacokinetic, Pharmacogenetic, Efficacy, Safety

1. To compare MK-4280A to standard of care (regorafenib or TAS-102) with respect to overall survival.

Secondary objectives 6

1. To compare MK-4280A to standard of care with respect to progression free survival per RECIST 1.1 as assessed by BICR.
2. To compare MK-4280A to standard of care with respect to objective response rate per RECIST 1.1 as assessed by BICR
3. To assess the efficacy of MK-4280A and standard of care with respect to duration of response per RECIST 1.1 by BICR.
4. To determine the safety and tolerability of MK-4280A and standard of care.
5. To compare the change from baseline in global health status/QoL, physical functioning, appetite loss and bloating for MK-4280A versus standard of care.
6. To compare the time to deterioration in global health status/QoL, physical functioning, appetite loss and bloating for MK-4280A versus standard of care.

Conditions and MedDRA coding

Colorectal Cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has a histologically confirmed colorectal adenocarcinoma that is metastatic and unresectable.
2. Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by the local site investigator.
3. Has been previously treated for the disease and radiographically progressed on or after or could not tolerate standard treatment.
4. Submits an archival (≤ 5 years) or newly obtained tumor tissue sample or newly obtained tumor tissue sample that has not been previously irradiated.
5. Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1 within 10 days prior to first dose of study intervention.
6. Has a life expectancy of at least 3 months, based on the investigator assessment.
7. Has the ability to swallow and retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption.
8. Has adequate organ function.

Exclusion criteria 21

1. Has previously been found to have deficient mismatch repair/microsatellite instability-high (dMMR/MSI-H) tumor status.
2. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis or leptomeningeal disease.
3. Has a history of acute or chronic pancreatitis.
4. Has neuromuscular disorders associated with an elevated creatine kinase (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
5. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
6. Has urine protein greater than or equal to 1g/24h.
7. A woman of childbearing potential who has a positive urine/serum pregnancy test within 24/72 hours prior to the first dose of study intervention.
8. Has received prior therapy with an anti-programmed cell death 1 (PD-1), anti-programmed death ligand 1 (PD-L1), or anti-programmed cell death ligand 2 (PD-L2), anti-lymphocyte activation gene 3 (LAG-3) antibody, with a tyrosine kinase inhibitor (TKI; eg, lenvatinib) other than rapidly accelerated fibrosarcoma (RAF) inhibitors (binimetinib is permitted if combined with a RAF inhibitor), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, cluster of differentiation [CD] 137).
9. Has previously received regorafenib or TAS-102.
10. Has received prior systemic anticancer therapy including investigational agents within 28 days before randomization.
11. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
13. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
15. Has an active autoimmune disease that has required systemic treatment in past 2 years.
16. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
17. Has an active infection requiring systemic therapy (eg, tuberculosis, known viral or bacterial infections, etc.).
18. Has a known history of human immunodeficiency virus (HIV) infection.
19. Has known history of Hepatitis B or known active Hepatitis C virus infection.
20. 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.
21. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 13

1. Progression-Free Survival (PFS) according per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)
2. Objective Response Rate (ORR) per RECIST 1.1 as Assessed by BICR
3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR
4. Number of Participants Who Experience at least One Adverse Event (AE)
5. Number of Participants Who Discontinue Study Treatment Due to an AE
6. Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
7. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
8. Change from Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score
9. Change from Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
10. Time to Deterioration (TTD) in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score
11. TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score
12. TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
13. TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue, P. O. Box 2000 P. O. Box 2000

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

David Fogelman

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

David Fogelman

Third parties 9

Locations

4 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 41 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications