| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Advanced/metastatic solid tumors |
|
| E.1.1.1 | Medical condition in easily understood language |
| Advanced Solid Tumors/ Cancers |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065252 |
| E.1.2 | Term | Solid tumor |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 1. To determine the safety and tolerability and to establish a preliminary maximum tolerated dose/recommended Phase 2 dose of MK-1088 administered as monotherapy and in combination with pembrolizumab infusion in Part 1 |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the PK of MK-1088 administered as monotherapy and in combination with pembrolizumab infusion in Part 1 and in Part 2.
2. To evaluate the anti-tumor activity (objective response rate [ORR] based on PCWG-modified RECIST 1.1 [prostate cancer participants only] or RECIST 1.1 [all other participants]) of MK-1088 as assessed by the investigator when used as monotherapy and in combination with pembrolizumab in Part 1 and in Part 2. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.The participant must have a histologically- or cytologically-confirmed diagnosis of advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for treatment known to confer clinical benefit
For metastatic castrate-resistant prostate cancer only:
•Must have previously received docetaxel, prior treatment with one other chemotherapy is allowed as well as up to 2 second-generation hormonal manipulations
•Have prostate cancer progression within 6 months before to screening, as determined by the investigator:
a.PSA progression using local laboratory values as defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each assessment where the PSA value at screening should be ≥2 ng/mL
b.Radiographic disease progression in soft tissue based on PCWG-modified RECIST 1.1 or RECIST 1.1 criteria with or without PSA progression
c.Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression
2.Disease per PCWG-modified RECIST 1.1 for mCRPC or measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Target lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
For participants with metastatic castrate-resistant prostate cancer:
a.Have PCWG-modified RECIST 1.1 measurable prostate cancer on CT or MRI scans as assessed by the local site/investigator/radiology
OR
b.Detectable bone metastases by whole body bone scintigraphy as per PCWG guidance
3.Is male or female, from minimum of 18 years of age inclusive, at the time of providing informed consent
4.If male, agrees to the following during the intervention period and for at least 7 days after the last dose of MK-1088:
•Abstains from heterosexual intercourse as their preferred and usual lifestyle and agrees to remain abstinent
OR
•Uses contraception unless confirmed to be azoospermic as detailed below:
-Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
-Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
5.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, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle,during the intervention period and for at least 7 days after the last dose of MK-1088 and for at least 120 days after the last dose of pembrolizumab, whichever occurs last after the last dose of study intervention
-Has a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
-Abstains from breastfeeding during the study intervention period and for at least 7 days after study intervention with MK-1088 or 120 days from the last dose of pembrolizumab
-Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
6.The participant has provided documented informed consent/assent for the study
7.Archival tumor tissue sample or newly obtained core needle biopsy of a tumor lesion not previously irradiated has been provided
8.Specimens must be collected within 72 hours before the start of study intervention
9.Have an ECOG Performance Status of 0 to 1 assessed within 72 hours prior to the first dose of study intervention
10.HIV-infected participants must have well controlled HIV on ART, defined as:
a.Participants on ART must have a CD4+ T-cell count >350 cells/mm3 at the time of screening
b.Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ using the locally available assay at the time of screening and for at least 12 weeks before screening
c.Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry
d.The combination ART regimen must not contain any antiretroviral medications other than: abacavir, dolutegravir, emtricitabine, lamivudine, raltegravir, rilpivirine, or tenoforvir
11.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 to treatment allocation
12.Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening
13.Be able to swallow and retain oral medication
|
|
| E.4 | Principal exclusion criteria |
1.Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks before the first dose of study intervention, or has not recovered to CTCAE Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
2.Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
3.Has clinically active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic, have no evidence of new or enlarging brain metastases, are evaluated within 4 weeks before first study intervention administration, and are off immunosuppressive doses of systemic steroids at least 2 weeks before enrollment
4.Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody/components of the study intervention
5.Has an active infection requiring therapy
6.Has a history of interstitial lung disease
7.Has a history of pneumonitis that required steroids or current pneumonitis
8.Has an active autoimmune disease that has required systemic treatment in the past 2 years
9.Has concurrent active Hepatitis B and Hepatitis C virus infection
10.HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease
11.Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
12.Has known psychiatric or substance abuse disorders that would interfere with the participant’s ability to cooperate with the requirements of the study
13.Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through the duration of contraception after the last dose of study intervention
14.Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study intervention administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study intervention administration and participants should be recovered
15.Has a history or current evidence of a GI condition or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications; 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, make administration of the study drugs hazardous, or make it difficult to monitor adverse effects such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
16. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including NYHA Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
17. Has a QTcF>470 msec.
18. History of an allogeneic stem cell transplant or solid organ transplant.
19. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor, AND was discontinued from that treatment due to a Grade 3 or higher irAE
20.Has received prior A2A or A2B receptor antagonist therapy
21.Currently receiving strong/moderate CYP3A4 inducers or inhibitors
22.Currently receiving H2 blockers or proton-pump inhibitors
23.Has received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation
24.Has received prior radiotherapy within 2 weeks of start of study intervention.
25.Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Refer to the protocol for information on COVID-19 vaccines
26. Has received an investigational agent or has used an investigational device within 4 weeks prior to intervention administration
27.Has a “superscan” bone scan. This is defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on screening bone scan such that the presence of additional metastases in the future could not be evaluated
28. Has not adequately recovered from major surgery or has ongoing surgical complications. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
2. Number of Participants Experiencing Adverse Events (AEs)
3. Number of Participants Discontinuing Study Treatment Due to AEs
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to ~21 days
2. Up to ~27 months
3. Up to ~24 months |
|
| E.5.2 | Secondary end point(s) |
1. Area Under the Plasma Concentration-Time Curve (AUC) of MK-1088
2. Maximum Plasma Concentration (Cmax) of MK-1088
3. Minimum Plasma Concentration (Cmin) of MK-1088
4. Objective Response Rate (ORR)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Pre-dose, 1, 2, 4, 8 hours post-dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 2 Day 2; Pre-dose on Cycles 3, 4 and every 4 cycles (up to ~27 months); Cycle = 21 days
2. Pre-dose, 1, 2, 4, 8 hours post-dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 2 Day 2; Pre-dose on Cycles 3, 4 and every 4 cycles (up to ~27 months); Cycle = 21 days
3. Pre-dose, 1, 2, 4, 8 hours post-dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 1 Day 2, Cycle 2 Day 2; Pre-dose on Cycles 3, 4 and every 4 cycles (up to ~27 months); Cycle = 21 days
4. Up to ~36 months
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | Yes |
| E.7.1.3.1 | Other trial type description |
| First administration in oncology patients |
|
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Part 1: dose escalation and confirmation: Part 2: cohort expansion |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Israel |
| United States |
| Switzerland |
| Denmark |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
