Pembrolizumab in combination with vibostolimab in relapsed or refractory hematologic malignancies

Phase 1

Active, not recruiting

• Conditions: Relapsed/refractory hematological malignancies; MedDRA version: 21.1Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001700-15-PL
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-27
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Cohort A
cHL
a)Diagnosis of cHL
b)Relapsed or refractory cHL to at least 1 prior line of therapy
c)Not been previously treated with an anti-PD-1 or anti-PD-L1 therapy
PMBCL
d)Diagnosis of PMBCL
e)Relapsed or refractory PMBCL to at least 2 prior lines of therapies
f)Relapsed or refractory to CAR-T-cell therapy or unable to receive it
g)Mus have previously received rituximab as part of prior treatment
h)Not been previously treated with an anti-PD-1-L1 therapy
2.Cohort B
cHL
a)Diagnosis of cHL
b)Relapsed or refractory cHL to at least 2 prior lines of therapies
c)Have progressed on treatment with an anti-PD-1/L1 mAb administered as monotherapy or with other checkpoint inhibitors or other therapies
PMBCL
d)Diagnosis of PMBCL
e)Relapsed or refractory PMBCL to at least 3 prior lines of therapies
f)Must have previously received rituximab as part of prior treatment
g)Relapsed or refractory to CAR-T-cell therapy or unable to receive it
h)Have progressed on treatment with an anti-PD-1/L1 mAb administered as monotherapy or with other checkpoint inhibitors or other therapies
3.Cohort C
a)Diagnosis of FL
b)Relapsed or refractory to at least 2 prior lines of therapy
c)Relapsed or refractory to CAR-T-cell therapy or unable to receive it
4.Cohort D
a)Diagnosis of DLBC.Cell of Origin is known for DLBCL,NOS,germinal center B-cell type or activated B-cell type
b)Must have progressed after at least 2lines of previous therapy,including progression after an auto-SCT,or are not a candidate for an auto-SCT
c)Relapsed or refractory to CAR-T-cell therapy or unable to receive it
d)Exhausted or be ineligible for or intolerant to all treatments
5.Cohort E
a)Histologically or cytologically confirmed diagnosis of active MM as per IMWG criteria
b)Measurable disease defined as meeting at least 1 of the following criteria:
i.Serum monoclonal protein (M-protein) levels =0.5 g/dL (=5 g/L),OR
ii.Urine monoclonal protein (M-protein) levels =200 mg/24 h,OR
iii.Abnormal FLC chain ratio (FLC k/l <0.26 or >1.65) with involved FLC level =100 mg/L (normal serum FLC k/l value: 0.26-1.65)
c)Must have undergone stem cell transplant and have relapsed after auto-SCT or have failed to achieve a CR or PR following auto-SCT,or is considered ineligible for auto-SCT
d)Participants must have received all regionally approved antimyeloma therapy including IMiD,proteasome inhibitor,steroids,anti-CD38 monoclonal antibody,selinexor, and anti BCMA therapies alone or in combination
e)Participants must have failed their last line of therapy
f)Relapsed or refractory to CAR-T-cell therapy or unable to receive it.
6.Cohort F
a)Have histologically confirmed diagnosis of B-cell lymphoma other than cHL,PMBCL,DLBCL,or FL,according to the WHO classification
b)Participants with MCL must have received prior Bruton's tyrosine kinase inhibitor therapy
c)Participants must have progressed after at least 2lines of previous therapy
d)Participant must have exhausted or be ineligible for or intolerant to all standard of care treatment options for their disease.
7.Cohorts A,B,C,D,and F:
a)Have measurable disease,defined as at least 1lesion that can be accurately measured in at least 2dimensions with spiral CT scan
b)Be able to provide newly obtained bone marrow biopsy material for tumor response assessment by local investigator sites
8.Cohort E (MM participants): Be able to provide newly obtained (within 3months) bone marrow biopsy or aspirate material for disease assessment and submit biomarker anal

Exclusion Criteria

1. For Cohort D and F (DLBCL and NHL): Has lymphoplasmacytic lymphomas, Waldenstrom’s macroglobulinemia, chronic lymphocytic leukemia (not associated with small lymphocytic lymphoma), Burkitt (-like) lymphoma, mature T cell and NK cell neoplasms, immunodeficiency associated lymphoproliferative neoplasms, or histiocytic and dendritic cell neoplasms.
2. For Cohort E (MM):
a) Has oligo-secretory myeloma, plasma cell leukemia, smoldering multiple myeloma, monoclonal gammopathy of undetermined significance.
b) History of primary amyloidosis, hyperviscosity or POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
3. For Cohort F (EBV+DLBCL): For patients with EBV+DLBCL should NOT be associated with a solid organ transplant.
4. Has known prior or current CNS involvement.
5. A WOCBP who has a positive urine pregnancy test within 72 hours before study intervention allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
6. 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.
7. 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.
8. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
9. Has received prior therapy with an mAb blocking TIGIT, an ani-TIGIT agent or an agent modulating the TIGIT axis, or an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (except where specified) or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
10. Any PMBCL participants in Cohort A and B that require the use of urgent cytoreductive therapy.
11. Has received prior systemic anticancer therapy, including investigational agents, within 2 weeks (small molecules like kinase inhibitors) or 4 weeks (chemotherapies and monoclonal antibodies) before cohort allocation.
12. If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
13. Has received prior radiotherapy within 2 weeks of start of study intervention.
14. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
15. 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.
16. Known severe hypersensitivity to MK-7684A, vibostolimab or pembrolizumab and/or any of its excipients.
17. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority.
18. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
19. Has an

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 1. Part 1: To determine the safety and tolerability of MK-7684A (Cohorts A to F);Secondary Objective: 1. Part 1: To evaluate ORR following administration of MK-7684A (Cohorts A to F) per disease-specific criteria as assessed by the investigator<br>2. Part 1: To evaluate the DOR following administration of MK-7684A (Cohorts A to F)<br>3. Part 1: To evaluate the DCR following administration of MK-7684A (Cohorts A to F)<br>4. Part 1: To characterize the PK profile of vibostolimab (Cohorts A to F)<br>;Primary end point(s): 1. Part 1: Number of Participants with a Dose-Limiting Toxicity (DLT)<br>2. Part 1: Number of Participants Who Experienced an Adverse Event (AE)<br>3. Part 1: Number of Participants Who Discontinued Study Treatment Due to an AE<br>;Timepoint(s) of evaluation of this end point: 1. Up to approximately 6 weeks <br>2. Up to approximately 27 months<br>3. Up to approximately 24 months<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Part 1: Objective Response Rate (ORR)<br>2. Part 1: Duration of Response (DOR)<br>3. Part 1: Disease Control Rate (DCR)<br>4. Part 1: Lowest Plasma Concentration (Ctrough) of Vibostolimab<br>5. Maximum Concentration (Cmax) of Vibostolimab<br>;Timepoint(s) of evaluation of this end point: 1. Up to approximately 24 months<br>2. Up to approximately 24 months<br>3. Up to approximately 24 months<br>4. Predose at Cycles 1, 2, 4, 8, and every 12 weeks afterwards (up to ~2 years). Cycle = 3 weeks<br>5. Postdose: after end of infusion (up to ~10 minutes) at Cycles 1 and 8. Cycle = 3 weeks<br>