NeoplasmsPhase 1NCT03918278
A Study of MK-0482 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-0482-001)
A Phase 1 study testing MK-0482, pembrolizumab and Paclitaxel in people with Neoplasms, run by Merck Sharp & Dohme LLC at 16 sites in 8 countries.
Trial summary
This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) dose of MK-0482 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms
- What is being tested?
- MK-0482, pembrolizumab and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 16 sitesin 8 countries
- Study dates
- 19 Jun 2019to 9 Jun 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Part 1 only: Has histologically-or cytologically-confirmed advanced/metastatic solid tumors and have received, been intolerant to, or been ineligible for, all treatments known to confer clinical benefit
- Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for Cohort B as assessed by the local site investigator/radiology
- Has provided an evaluable archival or newly obtained tumor tissue sample
- Part 1, Arm 1 only: Has ≥1 discrete malignant lesions that are amenable to biopsy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 95 days after the last dose of chemotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or agree to use contraception unless confirmed to be azoospermic
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- A female participant is eligible to participate if she is not pregnant or breastfeeding, and ≥1 of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 180 days after the last dose of chemotherapy or 120 days after the last dose of MK-0482 or pembrolizumab, whichever occurs last
- Part 2 Cohort A, C, and E only: WOCBP must also agree not to donate to others or freeze/store for her own use for the purpose of reproduction during and for at least 180 days after the last dose of chemotherapy
- Has a negative highly sensitive pregnancy test within 72 hours before the first dose of study treatment
- Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on anti-retroviral therapy (ART)
- Has adequate organ function
- Part 2 Cohort A only: 1) Has histologically confirmed locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) 2) Has received no prior systemic therapy for metastatic TNBC 3) Has tumor programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥1
- Part 2 Cohort B only: 1) Has confirmed diagnosis of GBM (isocitrate dehydrogenase (IDH) wildtype per 2021 World Health Organization (WHO) classification of tumors of central nervous system) 2) Has received a standard first-line treatment for GBM including surgery and radiation therapy with or without chemotherapy and evidence of disease recurrence or pression by magnetic resonance imaging (MRI) 3) Has time elapsed from prior treatment as per protocol 4) Has Karnofsky performance status (KPS) ≥ 80 within 7 days before start of study treatment 5) Is neurologically stable 6) Has known status of O6-methylguanine-DNA methyltransferase (MGMT) methylation and isocitrate dehydrogenase (IDH)
- Part 2 Cohort C only: Has histologically confirmed diagnosis of metastatic PDAC and has received no prior systemic therapy for metastatic pancreatic ductal adenocarcinoma (PDAC) including chemotherapy, biological or targeted therapy and has albumin ≥3.0 g/dL
- Part 2 Cohort D only: Has histologically confirmed diagnosis of locally advanced or metastatic soft tissue sarcoma (STS) and has received and progressed after one prior line of systemic treatment for advanced STS. Prior treatment in the (neo)adjuvant setting is not counted as a line of treatment for advanced disease
- Part 2 Cohort E only: Has histologically confirmed diagnosis of Stage IV or recurrent non-operable non-squamous non-small cell lung carcinoma (NSCLC) , has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS1) directed therapy is not indicated as primary therapy and has not received prior systemic treatment for metastatic NSCLC
Who cannot join
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years; with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
- Has known active central nervous system metastases and/or carcinomatous meningitis
- Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
- Has an active infection requiring systemic therapy
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- Has a history of interstitial lung disease
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- Has known Hepatitis B or C infection
- Has received prior systemic anticancer therapy, definitive radiotherapy, including investigational agents within 4 weeks (2 weeks for palliative radiation) before the first dose of study treatment
- Has received a live or live-attenuated vaccine within 30 days before the first dose of study treatment
- Has received an investigational agent or has used an investigational device 4 weeks prior to start of study intervention
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has had an allogeneic tissue/solid organ transplant in the last 5 years or has evidence of graft-versus-host disease
- Part 2 only: Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or prior therapy targeting other immune-regulatory receptors or mechanisms
- Part 2 Cohort A only: 1) Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months of start of study treatment 2) Has a known sensitivity to any component of paclitaxel or any of its excipients and 3) Is receiving any medication prohibited in combination with paclitaxel unless medication was stopped within 7 days before the start of study treatment
- Part 2 Cohort B only: 1) Has carcinomatous meningitis 2) Has recurrent tumor 3) Has tumor primarily localized to the brainstem or spinal cord 4) Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease 5) Has evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan except Grade ≤ Grade I and either post-operative OR stable on at least 2 consecutive MRI scans 6) Requires treatment with moderate or high dose systemic corticosteroids as defined in protocol for at least 3 consecutive days within 2 weeks of start of study treatment and 7) Optune® TTFields within 2 weeks of start of study treatment
- Part 2 Cohort C only: 1) Has a history of class II-IV congestive heart failure, cerebral vascular event, unstable angina, or myocardial infarction within 6 months of the start of study treatment 2) Has symptomatic ascites, and 3) Has a known hypersensitivity to nab-paclitaxel or gemcitabine, or any of their excipients
- Part 2 Cohort E only: 1) Has a diagnosis of small cell lung cancer 2) Has symptomatic ascites or pleural effusion 3)Is currently receiving either strong or moderate inhibitors and/or inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study 4) Is unable to interrupt aspirin or other NSAIDs, other than aspirin dose ≤1.3 g/day for a 5-day period 5) Is unable or unwilling to take folic acid or vitamin B12 supplementation, and 6) has a known hypersensitivity to carboplatin or pemetrexed, or any of their excipients
Trial locations and contacts
16 sites in 8 countries.
16 sites in 8 countries
United States3 sites
Henry Ford Health System ( Site 0002)
Detroit, Michigan, 48202
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0003)
Hackensack, New Jersey, 07601
Next Oncology ( Site 0001)
San Antonio, Texas, 78229
Australia2 sites
Macquarie University ( Site 0033)
Macquarie University, New South Wales, 2109
Alfred Health ( Site 0031)
Melbourne, Victoria, 3004
Canada2 sites
Princess Margaret Cancer Centre ( Site 0011)
Toronto, Ontario, M5G 2M9
BC Cancer - Vancouver Center ( Site 0010)
Vancouver, British Columbia, V5Z 4E6
Chile2 sites
FALP-UIDO ( Site 0100)
Santiago, Region M. de Santiago, 6900941
Bradfordhill-Clinical Area ( Site 0101)
Santiago, Region M. de Santiago, 8420383
Israel2 sites
Hadassa Ein Karem Medical Center ( Site 0022)
Jerusalem, 9112001
Chaim Sheba Medical Center ( Site 0020)
Ramat Gan, 5265601
Italy2 sites
Istituto Europeo di Oncologia IRCCS-Divisione di Sviluppo di Nuovi Farmaci per Terapie Innovative (
Milan, 20141
ospedale le scotte-U.O.C. Immunoterapia Oncologica ( Site 0091)
Siena, Tuscany, 53100
South Korea2 sites
Seoul National University Hospital ( Site 0061)
Seoul, 03080
Asan Medical Center ( Site 0060)
Seoul, 05505
About this study
Official title: A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors.
This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) dose of MK-0482 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit. Part 2 is expansion cohort to determine safety and tolerability of MK-0482 in combination with pembrolizumab with and without chemotherapy in participants with advanced tumor specific cohorts.
- Conditions
- Neoplasms
- Being tested
- MK-0482, pembrolizumab, Paclitaxel, Nab-paclitaxel, Gemcitabine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-0482Biological
IV infusion
pembrolizumabBiological
Also called MK-3475, KEYTRUDA®
IV infusion
PaclitaxelDrug
Also called Nov-Onxol, Onxol, Paclitaxel Novaplus, Taxol
IV infusion
Nab-paclitaxelDrug
Also called Abraxane
IV infusion
GemcitabineDrug
Also called Gemzar
IV infusion
CarboplatinDrug
Also called Paraplatin ®
IV infusion
PemetrexedDrug
Also called Alimta
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1: MK-0482 Monotherapy | Experimental | Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years). Receives: Biological: MK-0482 |
| Part 1: MK-0482 + Pembrolizumab Combination Therapy | Experimental | Participants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years). Receives: Biological: MK-0482; Biological: pembrolizumab |
| Part 2: Cohort A | Experimental | Participants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m^2 via IV infusion until PD or discontinuation. Receives: Biological: MK-0482; Biological: pembrolizumab; Drug: Paclitaxel |
| Part 2: Cohort B | Experimental | Participants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years). Receives: Biological: MK-0482; Biological: pembrolizumab |
| Part 2: Cohort C | Experimental | Participants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m^2 via IV infusion and gemcitabine 1000 mg/m^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation. Receives: Biological: MK-0482; Biological: pembrolizumab; Drug: Nab-paclitaxel; Drug: Gemcitabine |
| Part 2: Cohort D | Experimental | Participants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years). Receives: Biological: MK-0482; Biological: pembrolizumab |
| Part 2: Cohort E | Experimental | Participants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years). Receives: Biological: MK-0482; Biological: pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only)
DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
Measured: Cycle 1 (Up to 21 days)
Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Measured: Up to approximately 27 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
The number of participants who discontinue study treatment due to an AE will be presented.
Measured: Up to approximately 24 months
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 2 only)
DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
Measured: Up to approximately 28 days from the start of study intervention
Secondary outcomes (8)
Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
Cmin of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmin (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
Cmax of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 Cmax (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
AUC of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Blood samples will be obtained at designated time points for the assessment of MK-0482 AUC (Cycle 1 Day 1: Predose and at end of administration [within 30 minutes after the end of infusion]; Cycle 1 Days 2, 4, 8 and 15: Once daily; Cycles 2, 4, 6, 8 and every 4 cycles thereafter: Predose and at end of administration [within 30 minutes after the end of infusion]; and at end of treatment/discontinuation [Up to approximately 25 months]). Each cycle is 21 days.
Measured: At designated time points (Up to approximately 25 months)
Objective Response Rate (ORR) As Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Part 2 only)
ORR is defined as the percentage of participants who have 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) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.
Measured: Up to approximately 25 months
ORR As Assessed by Investigator per Response Assessment in Neuro-Oncology (RANO) (Part 2 only)
ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: sum of products of diameters decreased by ≥50% from baseline value) per RANO criteria. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RANO will be presented.
Measured: Up to approximately 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2019
- Study start19 Jun 2019
- Primary completion9 Jun 2025
- Study completion9 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 222 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
- NCT03918278
- Sponsor's protocol ID
- 0482-001
- Other IDs
- MK-0482-001, 2022-500821-34-00, U1111-1278-2766, 2020-004089-20
- Status last verified
- Jun 2025
- First submitted
- 15 Apr 2019
- Last updated
- 25 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors.
- ClinicalTrials.gov ID
- NCT03918278
- Acronym / sponsor ID
- 0482-001
- Conditions
- Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Jun 2019 (actual)
- Primary completion
- 9 Jun 2025 (actual)
- Study completion
- 9 Jun 2025 (actual)
- First posted
- 17 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 2 part study. Part 1 is a dose escalation to determine the safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) dose of MK-0482 administered as monotherapy and in combination with pembrolizumab (MK-3475) in participants with advanced solid tumors for which there is no available therapy which may convey clinical benefit. Part 2 is expansion cohort to determine safety and tolerability of MK-0482 in combination with pembrolizumab with and without chemotherapy in participants with advanced tumor specific cohorts.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part 1: MK-0482 Monotherapy | Experimental | Biological: MK-0482Participants receive escalating doses of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years). |
| Part 1: MK-0482 + Pembrolizumab Combination Therapy | Experimental | Biological: MK-0482, Biological: pembrolizumabParticipants receive escalating doses of MK-0482 via IV infusion + pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 administrations (up to approximately 2 years). |
| Part 2: Cohort A | Experimental | Biological: MK-0482, Biological: pembrolizumab, Drug: PaclitaxelParticipants with metastatic triple negative breast cancer (TNBC) first line treatment (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) and paclitaxel 90 mg/m^2 via IV infusion until PD or discontinuation. |
| Part 2: Cohort B | Experimental | Biological: MK-0482, Biological: pembrolizumabParticipants with recurrent non-operable glioblastoma (GBM) current treatment of second line (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years). |
| Part 2: Cohort C | Experimental | Biological: MK-0482, Biological: pembrolizumab, Drug: Nab-paclitaxel, Drug: GemcitabineParticipants with metastatic pancreatic ductal adenocarcinoma (PDAC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years), Nab-Paclitaxel 125 mg/m^2 via IV infusion and gemcitabine 1000 mg/m^2 via IV infusion until PD or unacceptable toxicity that requires discontinuation. |
| Part 2: Cohort D | Experimental | Biological: MK-0482, Biological: pembrolizumabParticipants with metastatic soft tissue sarcoma (STS) (2L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years). |
| Part 2: Cohort E | Experimental | Biological: MK-0482, Biological: pembrolizumab, Drug: Carboplatin, Drug: PemetrexedParticipants with metastatic non-squamous non-small cell lung carcinoma (NSCLC) (1L) receive MK-0482 via IV infusion plus pembrolizumab 200 mg via IV infusion plus Pemetrexed 500 mg/m^2 via IV infusion on Day 1 of each 21-day cycle (Q3W) up to 35 administrations (up to approximately 2 years) plus carboplatin with desired dose of area under the curve (AUC) 5 and pemetrexed 500 mg/m^2, both administered via IV infusion, followed by maintenance therapy with pemetrexed 500 mg/m^2 via IV infusion for up to a total of 35 administrations (up to approximately 2 years). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Part 1 only: Has histologically-or cytologically-confirmed advanced/metastatic solid tumors and have received, been intolerant to, or been ineligible for, all treatments known to confer clinical benefit
- Has measurable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) for Cohort B as assessed by the local site investigator/radiology
- Has provided an evaluable archival or newly obtained tumor tissue sample
- Part 1, Arm 1 only: Has ≥1 discrete malignant lesions that are amenable to biopsy
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
Key exclusion criteria (21 listed)
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- Has a known additional malignancy that is progressing or has required active treatment within the past 2 years; with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
- Has known active central nervous system metastases and/or carcinomatous meningitis
- Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAb) and/or any component of pembrolizumab (MK-3475) or MK-0482
- Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE)
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 |
|---|---|---|
| MK-0482IV infusion | Biological | Part 1: MK-0482 + Pembrolizumab Combination Therapy, Part 1: MK-0482 Monotherapy, Part 2: Cohort A, Part 2: Cohort B, Part 2: Cohort C, Part 2: Cohort D, Part 2: Cohort E |
| pembrolizumabAlso: MK-3475, KEYTRUDA®IV infusion | Biological | Part 1: MK-0482 + Pembrolizumab Combination Therapy, Part 2: Cohort A, Part 2: Cohort B, Part 2: Cohort C, Part 2: Cohort D, Part 2: Cohort E |
| PaclitaxelAlso: Nov-Onxol, Onxol, Paclitaxel Novaplus, TaxolIV infusion | Drug | Part 2: Cohort A |
| Nab-paclitaxelAlso: AbraxaneIV infusion | Drug | Part 2: Cohort C |
| GemcitabineAlso: GemzarIV infusion | Drug | Part 2: Cohort C |
| CarboplatinAlso: Paraplatin ®IV infusion | Drug | Part 2: Cohort E |
| PemetrexedAlso: AlimtaIV infusion | Drug | Part 2: Cohort E |
Primary outcome
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only)
Time frame: Cycle 1 (Up to 21 days)
DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
Number of Participants Who Experience at Least One Adverse Event (AE)
Time frame: Up to approximately 27 months
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Time frame: Up to approximately 24 months
The number of participants who discontinue study treatment due to an AE will be presented.
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 2 only)
Time frame: Up to approximately 28 days from the start of study intervention
DLTs defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr)4 nonhematologic toxicity (T); Gr4 hematologic T lasting ≥7 days, except thrombocytopenia (TCP); Gr4 TCP of any duration; Gr3 TCP associated with clinically-significant bleeding; nonhematologic adverse event (AE) ≥Gr3 in severity, with exceptions; Gr3/4 alanine transaminase (ALT), aspartate transaminase (AST), and/or bilirubin (bili) with exceptions; a protocol-defined elevation of ALT, AST, and bili; Gr3/4 nonhematologic laboratory abnormality if: clinically significant medical intervention is required, leads to hospitalization, persists for >1 week, or results in liver injury with exceptions; Gr3/4 febrile neutropenia; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx-related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 or any combination component during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
8 secondary outcomes
Minimum Serum Concentration (Cmin) of MK-0482 When Administered as Monotherapy (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
Cmin of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
Maximum Serum Concentration (Cmax) of MK-0482 When Administered as Monotherapy (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
Cmax of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
Area Under the Concentration-Time Curve (AUC) of MK-0482 When Administered as Monotherapy (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
AUC of MK-0482 When Administered in Combination with Pembrolizumab (Part 1 only)
Time frame: At designated time points (Up to approximately 25 months)
Objective Response Rate (ORR) As Assessed by Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Part 2 only)
Time frame: Up to approximately 25 months
ORR As Assessed by Investigator per Response Assessment in Neuro-Oncology (RANO) (Part 2 only)
Time frame: Up to approximately 25 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2025.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/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
16 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-0482, pembrolizumab and Paclitaxel in people with Neoplasms, run by Merck Sharp & Dohme LLC at 16 sites in 8 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 16 inclusion and 21 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: finished, as of the sponsor's last update on 25 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States, Australia, Canada, Chile, Israel and 3 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 Who Experience a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Part 1 only) (time frame: Cycle 1 (Up to 21 days)). The study lists 4 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 25 Jun 2025; AzTrials last refreshed its copy on 7 Nov 2026.