This study has been transitioned to CTIS with ID 2023-505284-36-00 check the CTIS register for the current data. Objective 1: To compare MK-7684A to pembrolizumab alone with respect to ORR in participants with cervical cancer whose tumors express PD…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Endpoint to objective 1: Objective response: A confirmed CR or PR
Endpoint to objective 2: PFS: The time from randomization to first documented
disease progression or death due to any cause, whichever occurs first
Endpoint to objective 3: Objective response: A confirmed CR or PR
Endpoint to objective 4: PFS: The time from first dose of study intervention to
first documented disease progression or death due to any cause, whichever
occurs first
Secondary outcome
1) Overall survival (OS)
2) Progression free survival (PFS)
3) The duration of response (DOR)
4) Change from baseline in HRQoL
5) Safety and tolerability of MK-7684A alone or in combination with other
anticancer therapies (measured by Adverse Events)
6) Objective response (confirmed CR or PR)
Background summary
In 2020, there were approximately 1.7 million newly diagnosed solid tumors in
the United States. About 25% of these patients were in stage IV disease at
diagnosis. For this group of patients chemotherapy is the only available
treatment option, while chemotherapy is associated with significant toxicities
and low response rates. For this patient population, there is an unmet medical
need for the development of alternative treatment options. Therefore, this
study will investigate the effect of a combination of Pembrolizumab and
Vibostolimab in various advanced solid tumors.
MK-7684A is a co-formulation of 200mg MK-3475 and 200mg MK-7684. Vibostolimab
(MK-7684) is a human anti-TIGIT monoclonal antibody that can bind to the TIGIT
receptors on the T cells of our immune system. Pembrolizumab (MK-3475) is a
human anti-PD-1 monoclonal antibody that can bind to the PD-1 receptors on the
T cells of our immune system. The PD-1 receptor and TIGIT-receptor ligand
interactions are major pathways hijacked by tumors to suppress immune control.
The normal function of PD-1 and TIGIT, expressed on the cell surface of
activated T- cells under healthy conditions, is to down-modulate unwanted or
excessive immune responses, including autoimmune reactions. As a consequence,
the PD-1/PD-L1 and TIGIT pathways are attractive targets for therapeutic
intervention in solid tumors.
Study objective
This study has been transitioned to CTIS with ID 2023-505284-36-00 check the CTIS register for the current data.
Objective 1: To compare MK-7684A to pembrolizumab alone with respect to ORR in
participants with cervical cancer whose tumors express PD-L1 (CPS >=1)
Objective 2: To compare MK-7684A to pembrolizumab alone with respect to PFS in
participants with cervical cancer whose tumors express PD-L1 (CPS >=1)
Objective 3: To evaluate MK-7684A alone or in combination with other anticancer
therapies with respect to ORR in participants with selected solid tumors,
excluding those with cervical cancer whose tumors express PD-L1 (CPS >=1)
Objective 4: To evaluate MK-7684A in combination with other anticancer
therapies with respect to PFS per RECIST 1.1 at 9 months (PFS-9) and 12 months
(PFS-12) as assessed by the investigator in participants with previously
untreated BRCA1/2 nonmutated and HRD-negative advanced epithelial ovarian
cancer enrolled in Cohort I
Study design
This is a non-randomised (with exception of cohort A, which will be 1:1
randomized), multicenter, multicohort, open-label, phase 2, basket-study with
MK-7684A, a co-formulation of vibostolimab (MK-7684) with pembrolizumab
(MK-3475), alone or in combination with other anticancer therapies in
participants with selected solid tumors.
About 610 participants will be assigned to the study. Screening procedures must
be completed within 28 (or 56) days prior to treatment. Eligible participants
are randomly assigned in cohort A1 or cohort A2 to cohort G to one of the
following study intervention groups, depending on the cancer type selected A
safety-lead-in will be performed to determine the tolerability and RP2D of
lenvatinib, 5 FU/cisplatin, and paclitaxel to be used in combination with MK
7684A. Additional dose levels are included in the safety lead-in only to
complete dose-finding and identification of the RP2D. Enrollment may be
expanded in the event intermediate dose levels are explored during the safety
lead-in to identify the RP2D for lenvatinib, 5 FU/cisplatin, and paclitaxel to
be used in combination with MK-7684A. Continued allocation into these cohorts
will only occur if the starting dose (ie, Dose Level 0) is determined to be the
RP2D.
With protocol amendement 05 new cohorts with different types of solid tumors
are added to evaluate safety and efficacy of MK7684A.
Intervention
The intervention differs per cohort. This concerns both the study drugs as well
as frequency, dose and duration. Potential study treatment consists of
pembrolizumab or MK7684A (combination of pembrolizumab and vibostolimab), which
could be combined with lenvatinib, chemotherapy (capecitabine, carboplatin,
cisplatin, docetaxel, fluorouracil (5-FU), gemcitabine, oxaliplatin,
paclitaxel) or bevacizumab. Refer to the protocol for a complete overview.
Study burden and risks
For this study, patients will be subjected to invasive procedures such as blood
collection, biopsy, CT, MRI or bone scans, physical exams, 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 up to a maximum of 35 treatments. It cannot
be guaranteed that participants in clinical studies will directly benefit from
study intervention during participation, as clinical studies are designed to
provide information about the safety and effectiveness of an investigational
medicine.
Pembrolizumab has been administered in a large number of cancer participants
with a well characterized safety profile and has received regulatory approval
for multiple malignancies. Overall, pembrolizumab is well tolerated at doses up
to 10 mg/kg every 2 weeks (Q2W). Pembrolizumab has also demonstrated anticancer
clinical activity and efficacy in a broad range of cancer indications.
Available clinical safety data indicated that vibostolimab is tolerable at
doses up to and including 700 mg, both when used as monotherapy and in
combination with pembrolizumab. No DLTs were observed at any of the
vibostolimab doses tested either as monotherapy or in combination with
pembrolizumab during the dose escalation and confirmation portion of Study
MK-7684-001, and the MTD was not reached.
Waarderweg 39
Haarlem 2031 BN
NL
Waarderweg 39
Haarlem 2031 BN
NL
Listed location countries
Age
Inclusion criteria
A participant will be eligible for inclusion in the study if the participant:
1. Has histologically or cytologically confirmed, advanced (locally recurrent
unresectable or metastatic) solid tumor as follows:
• Squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the
cervix
• Endometrial cancer
• Head and neck squamous cell carcinoma (HNSCC)
• Unresectable biliary adenocarcinoma (gallbladder or biliary tree
[intrahepatic or extrahepatic] cholangiocarcinoma)
• Adenocarcinoma or squamous cell carcinoma of the esophagus or
advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal
junction (GEJ)
• Triple-negative breast cancer (TNBC)
• Hepatocellular carcinoma (HCC)
• Urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra
• Ovarian cancer
• Gastric cancer
2. Has measurable disease per RECIST 1.1 as assessed by the BICR (Cohort A1
only) or local site investigator/radiology (all other cohorts)
3. Can provide a newly obtained core or excisional biopsy of a tumor lesion (or
archived tumor tissue sample)
4. Is male or female, who is at least 18 years of age at the time of signing
the informed consent
5. Has an ECOG Performance Status of either 0 or 1 (ECOG PS of 2 allowed for
Cohort H only), as assessed within 7 days before starting study intervention
6. Has a predicted life expectancy of at least 3 months
7. Male participants must agree to follow contraceptive guidance
8. Female participants are not pregnant or breastfeeding, not women of
child-bearing potential (WOCBP) or are WOCBP and agree to follow contraceptive
guidance
9. The participant has provided documented informed consent for the study
10. Has adequately controlled BP with or without antihypertensive medications.
Note: this criterion only applies to participants who will receive lenvatinib
11. HIV-infected participants must have well controlled HIV on ART
12. Participants who are HbsAg positive are eligible if they have received HBV
antiviral therapy for at least 4 weeks and have undetectable HBV viral load
before randomization/allocation
13. Participants with history of HCV infection are eligible if HCV viral load
is undetectable at Screening
14. Has adequate organ function
Exclusion criteria
Participant must be excluded from the study if the participant:
1. Has a history of a second malignancy, unless potentially curative treatment
has been completed with no evidence of malignancy for 3 years
2. HIV-infected participants with a history of Kaposi's sarcoma and/or
Multicentric Castleman's Disease
3. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or
anti-TIGIT agent
4. Has received prior systemic anticancer therapy including investigational
agents within 4 weeks. Note: This does not include lead in chemotherapy in
Cohort I
5. Has received prior radiotherapy within 2 weeks or radiation-related
toxicities requiring corticosteroids
6. Has received a live or live-attenuated vaccine within 30 days
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days
8. Has known active CNS metastases and/or carcinomatous meningitis
9. Known severe hypersensitivity (>=Grade 3) to study medication or any of their
excipients
10. Has an active autoimmune disease that has required systemic treatment in
past 2 years
11. Has a history of (noninfectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease
12. Has an active infection requiring systemic therapy
13. 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
14. Has present accumulation of pleural, ascitic, or pericardial fluid
requiring drainage or diuretic drugs within 2 weeks
15. Has concurrent active hepatitis B and hepatitis C infection
16. Has not adequately recovered from major surgery
17. Participants unlikely to comply with the requirements of the study
18. Has had an allogenic organ transplant
19. Has received an investigational agent or has used an investigational device
within 4 weeks before the first dose of study intervention
All Cohorts except B1:
20. Has known MSI-H or MMR deficient cancer
Cohort B1 and B2 only:
21. Greater than 1 prior systemic chemotherapy regimen
For participants who will receive Lenvatinib: Cohort B2 & G:
22. Has had major surgery within 3 weeks
23. Has current, clinically relevant >=Grade 3 fistula
24. Has urine protein >=1 g/24 hours
25. Has a LVEF below the normal range
26. Has radiographic evidence of encasement or invasion of a major blood
vessel, or of intratumoral cavitation
27. Has prolongation of QTc interval to >480 ms
28. Has clinically significant cardiovascular disease within 12 months
29. Has serious nonhealing wound, ulcer, or bone fracture
30. Has GI malabsorption
31. Has active hemoptysis
32. Has had esophageal or gastric variceal bleeding within the last 6 months (G
only)
Cohort D2:
33. Has had previous systemic therapy for advanced or unresectable biliary
tract cancer
Cohort F:
34. Has a history of class II-IV congestive heart failure or myocardial
infarction within 6 months
Cohort H:
35. Has disease suitable for local therapy administered with curative intent
36. Is receiving hemodialysis
Cohort I:
37. Has mucinous, germ cell, or borderline tumor of the ovary
38. Has ongoing Grade 3 or 4 toxicity, excluding alopecia, following
chemotherapy administered during the Lead-in Period
39. Has received colony-stimulating factors within 4 weeks prior to receiving
chemotherapy during the Lead-in Period
40. Is considered to be of poor medical risk due to a serious, uncontrolled
medical disorder, non-malignant systemic disease or active, uncontrolled
infection
41. Has had surgery <6 months prior to screening to treat borderline tumors,
early stage EOC or early stage fallopian tube cancer
42. Has uncontrolled hypertension
43. Has current, clinically relevant bowel obstruction (incl. subocclusive
disease), abdominal fistula or gastrointestinal perforation, related to
underlying EOC
44. Has a history of hemorrhage, hemoptysis or active gastrointestinal bleeding
within 6 months prior to allocation
45. Has received prior treatment for any stage of OC
46. Is a participant for whom intraperitoneal chemotherapy is planned or has
been administered as 1L therapy
47. Has severe hypersensitivity (>=Grade 3) to pembrolizumab, carboplatin,
paclitaxel, or bevacizumab and/or any of their excipients
48. Has resting ECG indicating uncontrolled, potentially reversible cardiac
conditions, as judged by the investigator or participant has congenital long QT
syndrome
49. Had either major surgery within 3 weeks of allocation or has not recovered
from major surgery
Cohort J:
50. Has squamous cell or undifferentiated gastric cancer
51. Has preexisting peripheral neuropathy >Grade 1
52. Has had previous therapy for locally advanced, unresectable or metastatic
gastric cancer
53. Has received prior therapy with an agent directed to a stimulatory or
co-inhibitory T-cell receptor
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 | CTIS2023-505284-36-00 |
| EudraCT | EUCTR2021-001009-56-NL |
| ClinicalTrials.gov | NCT05007106 |
| CCMO | NL77693.056.21 |