A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Coformulated quavonlimab (MK-1308)/pembrolizumab) Versus Other Treatments in Participants with Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)
- Conditions
- darmkankerdMMR (Mismatch Repair Deficient) colorectal cancermetastatic colorectal cancer10027656
- Registration Number
- NL-OMON53742
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
1. Has a histologically confirmed diagnosis of Stage IV CRCadenocarcinoma
2. Has locally confirmed dMMR/MSI-H.
3. Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or
immunotherapy for this disease.
4. Is male or female and at least 18 years of age at the time of providing
documented informed consent.
5. Has a life expectancy of at least 3 months.
6. Has ECOG Performance Status of 0 to 1 at Screening and within 3 days before
Cycle 1 Day 1 treatment.
7. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:
• Not a WOCBP
OR
• A WOCBP and uses a contraceptive method that is highly effective, or be
abstinent from heterosexual intercourse as their preferred and usual lifestyle
9. The participant (or legally acceptable representative) has provided
documented informed consent/assent for the study. The participant may also
provide consent/assent for FBR. However, the participant may participate in the
study without participating in FBR.
10. Have measurable disease per RECIST 1.1 as assessed by the site and verified
by BICR. Lesions situated in a previously irradiated area are considered
measurable if progression has been shown in such lesions.
11. Submit an archival (within 5 years of Screening) or newly obtained tumor
tissue sample that has not been previously irradiated;
12. Have adequate organ function.
1. Has received prior therapy with an agent directed to another stimulatory or
coinhibitory T-cell receptor (eg, PD 1, CTLA-4, OX-40, CD137, PD-L1, ILT-4,
LAG-3, TIGIT).
2. Has received prior systemic anticancer therapy including investigational
agents within 4 weeks before the first dose of study intervention.
3. If the participant had a surgery and they have not recovered adequately from
the procedure and/or any complications from the surgery before starting study
intervention.
4. Has received prior radiotherapy within 2 weeks of start of study
intervention.
5. Has received a live or live-attenuated vaccine within 30 days before the
first dose of study intervention.
6. Is currently participating in or has participated in a study of an
investigational agent or has used an investigational device within 4 weeks
before the first dose of study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to
the first dose of study medication.
8. Has a known additional malignancy that is progressing or has required active
treatment within the past 2 years.
9. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided
they are radiologically stable, (ie, without evidence of progression) for at
least 4 weeks by repeat imaging
10. Has severe hypersensitivity (>=Grade 3) to pembrolizumab, quavonlimab,
favezelimab, vibostolimab, MK-4830, and/or any of their excipients.
11. Has an active autoimmune disease that has required systemic treatment in
past 2 years
12. Has a history of (noninfectious) pneumonitis that required steroids or has
current pneumonitis.
13. Has a history of acute or chronic pancreatitis.
14. Has neuromuscular disorders associated with an elevated creatine
15. Has urine protein >=1 g/24h.
16. Has an active infection requiring systemic therapy (eg, tuberculosis, known
viral or bacterial infections, etc.).
17. Has a known history of HIV infection.
18. Concurrent active Hepatitis B and Hepatitis C virus infection.
19. Has clinically significant cardiac disease, including unstable angina,
acute myocardial infarction within 6 months from Day 1 of study intervention
administration.
20. Has present or progressive accumulation of pleural, ascitic, or pericardial
fluid requiring drainage or diuretic drugs within 2 weeks before
randomization/allocation.
21. 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.
22. Has a known psychiatric or substance abuse disorder that would interfere
with the participant's ability to cooperate with the requirements of the study.
23. Has had an allogenic tissue/solid organ transplant.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Objective (Cohort B): To compare MK-1308A, MK-4280A, MK-7684A,<br /><br>MK-4830+Pembrolizumab, and pembrolizumab mono-therapy with respect to Objective<br /><br>Response Rate per RECIST 1.1 as assessed by Blinded Independent Central Review</p><br>
- Secondary Outcome Measures
Name Time Method <p>To evaluate Duration of Response<br /><br><br /><br>To compare MK-1308A, MK-4280A, MK-7684A, MK-4830+Pembrolizumab, and<br /><br>pembrolizumab monotherapy with respect to Progression-Free Survival<br /><br><br /><br>To compare MK-1308A, MK-4280A, MK-7684A,MK-4830+Pembrolizumab, and<br /><br>pembrolizumab monotherapy with respect to Objective Response Rate<br /><br><br /><br>To compare MK-1308A, MK-4280A, MK-7684A, MK-4830+Pembrolizumab, and<br /><br>pembrolizumab monotherapy with respectt o Overall Survival<br /><br><br /><br>To evaluate the safety and tolerability of MK-1308A, MK-4280A, MK-7684A,<br /><br>MK-4830+Pembrolizumab, and compared to pembrolizumab<br /><br>monotherapy</p><br>