NeoplasmPhase 1NCT03099161
Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)
A Phase 1 study testing preladenant and pembrolizumab in people with Neoplasm, run by Merck Sharp & Dohme LLC at 5 sites in 3 countries.
Trial summary
The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm
- What is being tested?
- preladenant and pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 27 Jun 2017to 21 Feb 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
- Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
- Has measurable disease per RECIST 1.1
- Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Females must not be pregnant
- Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study therapy, throughout the study period, and for up to 120 days after the last dose of study therapy
Who cannot join
- Has disease that is suitable for local treatment administered with curative intent
- Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
- Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
- Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
- Is currently taking or has taken drugs that interfere with Cytochrome P450 (CYP)3A4 or CYP2C8 or grapefruit and star fruit in diet within 14 days of the first dose of study therapy
Show all 24Show fewer
- Is currently taking or has taken proton pump inhibitors within 5 days of the first dose of study therapy
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of the first dose of study therapy
- Is expected to require any other form of systemic or localized antineoplastic therapy while on study
- Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
- Has clinically active central nervous system metastases and/or carcinomatous meningitis
- History of a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study drug
- Has an active infection requiring therapy
- History of interstitial lung disease
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- History of active tuberculosis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has received a live-virus vaccine within 30 days of the first dose of study therapy
- Has known Human Immunodeficiency Virus (HIV) (HIV 1 or 2 antibodies) and/or known active and acute Hepatitis B or C infections
- Has known psychiatric or substance abuse disorders that would interfere with the ability to cooperate with the requirements of the study
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
- Has not fully recovered from any effects of major surgery without significant detectable infection
- Has had surgery that required general anesthesia within 2 weeks of the first dose of study therapy
- Has had surgery that required regional/epidural anesthesia within 72 hours of the first dose of study therapy
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Canada2 sites
Jewish General Hospital ( Site 0011)
Montreal, Quebec, H9H 4M7
Princess Margaret Hospital ( Site 0010)
Toronto, Ontario, H9H 4M7
Israel2 sites
Rambam Health Care Campus ( Site 0020)
Haifa
Tel Aviv Sourasky Medical Center ( Site 0021)
Tel Aviv
United States1 site
START Midwest ( Site 0001)
Grand Rapids, Michigan, 49546
About this study
Official title: A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies
The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .
- Conditions
- Neoplasm
- Being tested
- preladenant, pembrolizumab
- Keywords
- Advanced Solid Tumor, Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), PD1, PD-1, PDL1, PD-L1
- Medical subject headings
- Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
preladenantDrug
Also called MK-3814A
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
pembrolizumabBiological
Also called KEYTRUDA®, MK-3475
Administered as IV infusion on Day 1 of each 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Preladenant 25 mg Twice a Day (BID) | Experimental | During an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered. Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles. Receives: Drug: preladenant |
| Preladenant 50 mg BID | Experimental | During an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was established based on the number of DLTs at each dose level administered. Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles. Receives: Drug: preladenant |
| Preladenant + Pembrolizumab | Experimental | During an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles). Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles. Receives: Drug: preladenant; Biological: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.
Measured: Cycle 1 (up to 21 days)
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.
Measured: Up tp approximately 8 months
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to approximately 8 months
Secondary outcomes (1)
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review. The ORR per RECIST 1.1 for participants is presented.
Measured: Up to approximately 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start27 Jun 2017
- Primary completion24 Nov 2017
- Study completion21 Feb 2018
Why it stopped: The data did not support study endpoints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03099161
- Sponsor's protocol ID
- 3814A-062
- Other IDs
- MK-3814A-062
- Status last verified
- Feb 2019
- First submitted
- 30 Mar 2017
- Last updated
- 5 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies
- ClinicalTrials.gov ID
- NCT03099161
- Acronym / sponsor ID
- 3814A-062
- Conditions
- Neoplasm
- Keywords
- Advanced Solid Tumor, Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), PD1, PD-1, PDL1, PD-L1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The data did not support study endpoints
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2017 (actual)
- Primary completion
- 24 Nov 2017 (actual)
- Study completion
- 21 Feb 2018 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 5 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Preladenant 25 mg Twice a Day (BID) | Experimental | Drug: preladenantDuring an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered. Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles. |
| Preladenant 50 mg BID | Experimental | Drug: preladenantDuring an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was established based on the number of DLTs at each dose level administered. Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles. |
| Preladenant + Pembrolizumab | Experimental | Drug: preladenant, Biological: pembrolizumabDuring an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles). Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
- Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
- Has measurable disease per RECIST 1.1
- Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Females must not be pregnant
Key exclusion criteria (24 listed)
- Has disease that is suitable for local treatment administered with curative intent
- Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
- Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
- Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| preladenantAlso: MK-3814AAdministered as an oral capsule BID on Days 1 through 21 of each 21-day cycle | Drug | Preladenant + Pembrolizumab, Preladenant 25 mg Twice a Day (BID), Preladenant 50 mg BID |
| pembrolizumabAlso: KEYTRUDA®, MK-3475Administered as IV infusion on Day 1 of each 21-day cycle | Biological | Preladenant + Pembrolizumab |
Primary outcome
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (up to 21 days)
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.
Number of Participants Who Experienced at Least One Adverse Event (AE)
Time frame: Up tp approximately 8 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to approximately 8 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
1 secondary outcome
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Up to approximately 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing preladenant and pembrolizumab in people with Neoplasm, run by Merck Sharp & Dohme LLC at 5 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada, Israel, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (up to 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2019.