This study has been transitioned to CTIS with ID 2022-502100-70-00 check the CTIS register for the current data. The aim of this research is:1. To test the safety of MK-1308A, MK-4280A, MK-7684A and MK 4830 + pembrolizumab against pembrolizumab as…
ID
Source
Brief title
Condition
- Other condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Health condition
darmkanker
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Objective (Cohort B): To compare MK-1308A, MK-4280A, MK-7684A,
MK-4830+Pembrolizumab, and pembrolizumab mono-therapy with respect to Objective
Response Rate per RECIST 1.1 as assessed by Blinded Independent Central Review
Secondary outcome
To evaluate Duration of Response
To compare MK-1308A, MK-4280A, MK-7684A, MK-4830+Pembrolizumab, and
pembrolizumab monotherapy with respect to Progression-Free Survival
To compare MK-1308A, MK-4280A, MK-7684A,MK-4830+Pembrolizumab, and
pembrolizumab monotherapy with respect to Objective Response Rate
To compare MK-1308A, MK-4280A, MK-7684A, MK-4830+Pembrolizumab, and
pembrolizumab monotherapy with respectt o Overall Survival
To evaluate the safety and tolerability of MK-1308A, MK-4280A, MK-7684A,
MK-4830+Pembrolizumab, and compared to pembrolizumab
monotherapy
Background summary
CRC is a serious, life-threatening condition. he incidence of CRC reported in
2018 was ~1.8M (~10% of all cancers), and the number of worldwide
cancer-related deaths due to CRC was ~881,000, making it the second leading
cause of cancer death worldwide. Stage at diagnosis is the most important
predictor of survival. The 5-year relative survival rate for CRC was
approximately 64% with only 14% for distant disease (22% of CRC patients at
diagnosis). Mismatch repair deficient or MSI-H CRC comprises approximately 15%
of CRC. While dMMR/MSI-H CRC has a prognostic advantage in earlier stage
disease, this advantage is less pronounced upon disease recurrence (worse PFS
and OS). In previous studies, pembrolizumab monotherapy showed significant
efficacy in 1L or 2L+, however, even with this improvement in outcomes, there
remains a need for
still more progress. Another unmet need is treatment options for patients who
initially respond to pembrolizumab monotherapy, but whose disease subsequently
progresses despite continued treatment.
Therefore, it might be beneficial to make use of different effects on the
immune system from different pathways by adding a second checkpoint inhibitor.
This study investigates the potential benefit of the combination of
pembrolizumab with Quavonlimab, Favezelimab, Vibostolimab and MK-4830
(coformulations)
Study objective
This study has been transitioned to CTIS with ID 2022-502100-70-00 check the CTIS register for the current data.
The aim of this research is:
1. To test the safety of MK-1308A, MK-4280A, MK-7684A and MK 4830 +
pembrolizumab against pembrolizumab as the single agent.
2. To test how well MK-1308A, MK-4280A, MK-7684A and MK-4830 + pembrolizumab
are tolerated by participants versus pembrolizumab alone.
3. To test how well MK-1308A, MK-4280A, MK-7684A and MK-4830 + pembrolizumab
work against pembrolizumab alone.
4. See if participants receiving MK-1308A, MK-4280A, MK-7684A, or MK-4830 +
pembrolizumab live longer compared to participants receiving pembrolizumab
alone.
5. See if participants receiving MK-1308A, MK-4280A, MK-7684A, or MK-4830 +
pembrolizumab have a better quality of life compared to participants receiving
pembrolizumab alone.
6. Measure what happens as the study drugs pass through the body.
7. Seeing how the immune system responds to the study drugs.
Study design
This is a randomized, multicenter, open-label, phase 2 trial of multiple
investigational agents for the treatment of patients with chemotherapy-naïve
chemotherapy-naïve colorectal cancer with microsatellite instability-high
(MSI-H) or mismatch repair deficient (dMMR) stage IV colorectal cancer .
After a screening period of up to 28 days, participants will be randomized 1:5
to 1 of the following groups from Cohort B. (The Netherlands does not
participate in Cohort A). In the Netherlands approximately 3 participants will
participate in the study.
• Group 1. The people in this group receive only pembrolizumab every 6 weeks.
• Group 2. The people in this group receive the study drug MK-1308A
(quavonlimab + pembrolizumab) every 6 weeks
• Group 3. The people in this group receive the study drug MK-4280A
(favezelimab + pembrolizumab) every 3 weeks.
• Group 4. The people in this group receive the study drug MK-7684A
(vibostolimab + pembrolizumab) every 3 weeks.
• Group 5. The people in this group receive the study drug MK-4830 together
with pembrolizumab every 3 weeks.
All study drugs will be administered through an IV. MK-4830 and pembrolizumab
are administered via a separate infusion. Pembrolizumab is given first. After
this, about 30 minutes later, MK-4830 is given. All other study drugs will be
given through a single infusion. Treatment with pembrolizumab alone and
MK-1308A is given up to 17 times. Treatment with MK-4280A, MK-7684A and
MK-4830+pembrolizumab is given up to 35 times.
Adverse reactions will be monitored throughout the study and graded in severity
according to the guidelines outlined in the NCI CTCAE v5.0. Each participant
will be checked for AE's and SAE'
Intervention
Cohort B:
- Pembro monotherapy: 400 mg - IV -Q6W up to 17 doses
- MK1308A - 25 mg/400 mg - IV - Q6W up to 17 doses
- MK4280A - 800 mg MK- 4280 + 200 mg MK- 3475 ; IV ; Q3W up to 35 doses
- MK7684A - 200 mg MK- 7684 + 200 mg MK- 3475 ; IV ; Q3W up to 35 doses
- MK4830 + Pembro; 800 mg MK- 4830 + 200 mg MK- 3475 ; IV ; Q3W up to 35 doses
Study burden and risks
For this study, patients will be subjected to invasive procedures such as blood
collection, Biopsy, CT-MRI or bone scans, physicalexams, possibly
confrontational questionnaires, and patients will be asked to visit the
hospital regularly. Patients will be administered with different combination
therapies, during three-week cycles. It cannot be guaranteed that participants
in clinicalstudies will directly benefit from study intervention during
participation, as clinical studies are designed to provide information aboutthe
safety and effectiveness of an investigational medicine.
Waaderweg 39
Haarlem 2031 BN
NL
Waaderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2022-502100-70-00 |
| EudraCT | EUCTR2020-005114-18-NL |
| ClinicalTrials.gov | NCT04895722 |
| CCMO | NL82990.041.22 |