Solid TumorsPhase 1NCT03010176
Study of Ulevostinag (MK-1454) Alone or in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Solid Tumors or Lymphomas (MK-1454-001)
A Phase 1 study testing Ulevostinag and Pembrolizumab in people with Solid Tumors and Lymphoma, run by Merck Sharp & Dohme LLC at 19 sites in 5 countries.
Trial summary
The purpose of this study is to identify a maximum tolerated dose (MTD) or maximum administered dose (MAD) of ulevostinag alone and of ulevostinag in combination with pembrolizumab in participants with advanced/metastatic solid tumors or lymphomas in Part 1, and to evaluate the safety and efficacy of ulevostinag via… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Lymphoma
- What is being tested?
- Ulevostinag and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 19 sitesin 5 countries
- Study dates
- 3 Feb 2017to 21 Apr 2022
- 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
- All Arms and Cohorts (Parts 1 and 2):
- Has ≥1 injectable lesion which is measurable and amenable to injection and biopsy.
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Demonstrates adequate organ function within 7 days prior to treatment initiation.
- Female participants of childbearing potential must be using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse (on a long-term and persistent basis) during the intervention period and for at least 130 days after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for personal use for the purpose of reproduction during this period. Male participants must agree to refrain from donating sperm PLUS either be abstinent from heterosexual intercourse (on a long-term and persistent basis) OR agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse contraception, unless confirmed to be azoospermic (vasectomized) during the intervention period and for at least 130 days after the last dose of study intervention.
- Human Immunodeficiency (HIV)-infected participants must meet these additional criteria: a) Has laboratory-test-documented HIV-1 infection; b) Has well-controlled HIV on anti-retroviral therapy (ART), defined as: 1) must have a cluster of differentiation (CD4+) T-cell count >350 cells/mm^3 at time of screening; 2) must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the lower limit of quantification (LLOQ) using the locally available assay at the time of screening and for ≥12 weeks prior to screening; and, 3) must have been on a stable regimen, without changes in drugs or dose modification, for ≥4 weeks prior to study entry (Day 1).
Show all 28Show fewer
- All Part 1 Arms:
- -Has ≥1 distant, discrete non-injected lesion which is amenable to biopsy. This lesion must be measurable as defined by the response criteria used to assess the participant (RECIST 1.1 for solid tumors or revised International Working Group [IWG] criteria for lymphomas).
- Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions) and Part 1 Arm 2: Ulevostinag+Pembro (Cut/Subcut Lesions):
- Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor or lymphoma by pathology report and who has received, or been intolerant to, all treatment known to confer clinical benefit. Solid tumors and lymphomas of any type are eligible for enrollment.
- Has stage III or stage IV disease that is not surgically resectable. Stage IIB (T3N0M0B0-1) cutaneous T cell lymphoma (CTCL) participants are eligible.
- Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions):
- Has stage III or stage IV disease that is not surgically resectable.
- Has metastatic liver involvement that does not exceed one third of the total liver volume in participants to be treated by liver IT injection. Hepatocellular carcinoma participants are excluded from eligibility of IT liver injection.
- All Part 2 Expansion Cohorts:
- Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory:
- Has HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx; anti-PD-1/PD-L1 refractory metastatic or recurrent. Participants may not have a primary tumor site of the nasopharynx (any histology).
- Has histologically confirmed Stage III, IVa, or IVb disease per TNM (Tumor, Nodes, Metastasis) staging, American Joint Committee on Cancer (AJCC, 8th edition), with recurrent or persistent disease after definitive chemoradiation, deemed unresectable and considered refractory to both platinum-based combination chemotherapy and anti-programmed cell death-ligand 1 (anti-PD-1/PD-L1) antibody therapy.
- OR
- Has histologically confirmed Stage IVc disease per TNM staging, AJCC 8th edition, considered refractory to platinum-based combination chemotherapy and anti-PD-1/PD-L1 antibody therapy.
- Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC:
- Has confirmed unresectable locally advanced or metastatic TNBC as locally determined according to the American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines on a newly obtained core or excisional biopsy from a metastatic, not previously irradiated, tumor lesion.
- Has received at least one prior systemic treatment for metastatic breast cancer and has intolerance to, or documented disease progression on or after their most recent therapy.
- Has been previously treated with an anthracycline and/or taxane in the (neo)adjuvant or metastatic setting unless there was a medical contraindication to this treatment regimen.
- Have lactate dehydrogenase (LDH) <2.5 × upper limit of normal (ULN)
- Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver:
- Has histologically or cytologically confirmed Stage IV solid tumor that is not surgically resectable.
- Complete resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or baseline (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.
Who cannot join
- All Arms and Cohorts (Parts 1 and 2):
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 from the adverse events due to cancer therapeutics administered >4 weeks earlier.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and has received study therapy or has used an investigational device within 28 days of administration of ulevostinag. Note: Prior exposure to immunotherapeutics is allowed, including PD-1 and PD-L1 inhibitors
- Is expected to require any other form of antineoplastic therapy while on study.
- Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤ 10 mg/day is acceptable), or on any other form of immunosuppressive medication.
- Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 2 years.
Show all 27Show fewer
- Has clinically active central nervous system metastases and/or carcinomatous meningitis.
- Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- Has a history of vasculitis.
- Has an active infection requiring therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
- Has Hepatitis B or C infection(s).
- 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, and is free of significant detectable infection.
- Has received a live vaccine within 30 days prior to first dose of study drug.
- Has a history of re-irradiation for squamous cell carcinoma of the head \& neck (HNSCC) at the projected injection site.
- Has a tumor(s) in direct contact or encases a major blood vessel, and has ulceration and/or fungation onto the skin surface at the projected injection site.
- HIV-infected participants with history of Kaposi's sarcoma and/or multicentric Castleman's disease
- HIV-infected participants who have had an HIV-related opportunistic infection within 6 months
- Has been treated with a Stimulator of Interferon Genes (STING) agonist (e.g. ulevostinag, ADU-S100).
- All Part 2 Expansion Cohorts:
- Has experienced weight loss >10% over 2 months prior to first dose of study treatment.
- Has clinically relevant ascites at baseline (defined as requiring paracentesis) or with moderate radiographic ascites. A minimal amount of radiographic ascites is allowed.
- Has a history of interstitial lung disease.
- For Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver, participants with MSI-H CRC are excluded.
Trial locations and contacts
19 sites in 5 countries.
19 sites in 5 countries
United States10 sites
University of Alabama ( Site 0009)
Birmingham, Alabama, 35294
Mary Crowley Cancer Research Center ( Site 0001)
Dallas, Texas, 75230
Henry Ford Health System ( Site 0014)
Detroit, Michigan, 48202
Mount Sinai Hospital ( Site 0002)
New York, New York, 10029
Columbia University ( Site 0003)
New York, New York, 10032
UPMC Hillman Cancer Center ( Site 0013)
Pittsburgh, Pennsylvania, 15232
Huntsman Cancer Institute ( Site 0004)
Salt Lake City, Utah, 84112
University of California San Francisco ( Site 0007)
San Francisco, California, 94143
UCSF ( Site 0015)
San Francisco, California, 94158
UCLA Medical Center ( Site 0005)
Santa Monica, California, 90404
France3 sites
Institut Curie ( Site 0050)
Paris, 75005
Institut Claudius Regaud ( Site 0051)
Toulouse, Haute-Garonne, 31059
Institut Gustave Roussy ( Site 0049)
Villejuif, Val-de-Marne, 94805
Israel2 sites
Rambam Medical Center ( Site 0041)
Haifa, 3109601
Sheba Medical Center ( Site 0040)
Ramat Gan, 5265601
South Korea2 sites
Severance Hospital ( Site 0103)
Seoul, 03722
Asan Medical Center ( Site 0104)
Seoul, 05505
United Kingdom2 sites
The Royal Marsden Foundation Trust ( Site 0031)
London, London, City of, SW3 6JJ
The Royal Marsden NHS Foundation Trust. ( Site 0032)
Sutton, Surrey, SM2 5PT
About this study
Official title: Phase 1 Open-label, Multicenter Study of MK-1454 Administered by Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors or Lymphomas
The purpose of this study is to identify a maximum tolerated dose (MTD) or maximum administered dose (MAD) of ulevostinag alone and of ulevostinag in combination with pembrolizumab in participants with advanced/metastatic solid tumors or lymphomas in Part 1, and to evaluate the safety and efficacy of ulevostinag via intratumoral (IT) injection in combination with pembrolizumab in selected solid tumors in Part 2.
Ulevostinag will be administered IT; pembrolizumab (pembro) will be administered via intravenous (IV) infusion. In Part 1, participants will be allocated to one of three treatment arms: ulevostinag monotherapy (cutaneous/subcutaneous [cut/subcut] lesions), ulevostinag +pembro (cut/subcut lesions), or ulevostinag +pembro (visceral lesions).
In Part 2, participants with head and neck squamous cell carcinoma (HNSCC) who are anti-programmed cell death-protein 1 or anti-programmed cell death-ligand 1 (anti-PD-1/PD-L1) refractory or with anti-PD-1/PD-L1 treatment (TrT)-naïve triple-negative breast cancer (TNBC) or with anti-PD-1/PD-L1 TrT-naïve solid tumors with liver metastases/lesions will receive ulevostinag via IT injection at the preliminary Recommended Phase 2 Dose (RP2D) determined in Part 1 PLUS pembrolizumab via IV infusion for up 35 cycles (up approximately 2 years).
Read the detailed description
Participants will receive either ulevostinag monotherapy or ulevostinag in combination with pembrolizumab for up to 35 cycles (approximately 2 years). Participants will undergo at least a 24-hour inpatient observation period following the first dose administration of ulevostinag on Cycle 1 Day 1 in Part 1. For Part 2, the length of the observation period following administration of the first dose of ulevostinag on Cycle 1 Day 1 is at least 8 hours.
- Conditions
- Solid Tumors, Lymphoma
- Being tested
- Ulevostinag, Pembrolizumab
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Intratumoral (IT)
- Medical subject headings
- Lymphoma, 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.
UlevostinagDrug
Also called MK-1454
IT injection
PembrolizumabBiological
Also called MK-3475, Keytruda®
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions) | Experimental | Participants with cutaneous (cut) or subcutaneous (subcut) lesions will receive escalating doses of ulevostinag monotherapy via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond for up to 35 cycles (up to approximately 2 years). Receives: Drug: Ulevostinag |
| Part 1 Arm 2: Ulevostinag +Pembro (Cut/Subcut Lesions) | Experimental | Participants with cut or subcut lesions will receive escalating doses of ulevostinag via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond PLUS pembrolizumab (pembro) via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). Receives: Drug: Ulevostinag; Biological: Pembrolizumab |
| Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions) | Experimental | Participants with visceral lesions will receive escalating dose frequencies of ulevostinag via IT injection at escalating dose frequencies (Day 1 of each 21-day cycle for up to 35 cycles, then Days 1 and 8 of each 21-day cycle for two cycles, then Day 1 of each 21 day cycle up to 35 cycles, then Days 1, 8, and 15 of each 21-day cycle for two cycles followed by Day 1 of each 21-day cycle up to 35 cycles, PLUS pembrolizumab IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years). Receives: Drug: Ulevostinag; Biological: Pembrolizumab |
| Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory | Experimental | Participants with HNSCC who are anti-programmed cell death-1 or anti-programmed cell death-ligand 1 refractory will receive ulevostinag at the preliminary Recommended Phase 2 Dose (RP2D) determined by dose escalation in Part 1 Arm 1 and 2 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). Receives: Drug: Ulevostinag; Biological: Pembrolizumab |
| Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC | Experimental | Participants with TNBC who are anti-PD-1/PD-L1 treatment-naïve or who have refractory unresectable locally advanced or metastatic TNBC will receive ulevostinag at the preliminary RP2D determined by dose escalation in Part 1 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). Receives: Drug: Ulevostinag; Biological: Pembrolizumab |
| Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver | Experimental | Participants with solid tumors with liver metastases/lesions who are anti-PD-1/PD-L1 treatment-naïve will receive ulevostinag at the preliminary RP2D based on Part 1: ulevostinag + pembro (visceral lesions) treatment arm via IT injection in a to-be-determined dose and frequency, based on data from Arm 3, PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). Receives: Drug: Ulevostinag; Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE 4.0)
DLTs were assessed during the first cycle (21 days) \& are defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia, Gr 3 thrombocytopenia (if associated with clinically significant bleeding); nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for >1 week); Gr 3 or 4 febrile neutropenia; drug-related toxicity that causes treatment discontinuation or dose delay >7 days between consecutive doses during Cycle 1; drug-related toxicity that causes a >2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is ≥3× upper limit of normal (ULN) \& an elevated total bilirubin value ≥2× ULN \& an alkaline phosphatase value <2× ULN, in which no alternative reasons can be found; ≥Gr 2 immune-mediated uveitis; or Gr 5 toxicity.
Measured: Cycle 1 (21-day cycle)
Parts 1 and 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
Measured: Up to approximately 2 years
Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an AE
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
Measured: Up to approximately 2 years
Secondary outcomes (5)
Parts 1 and 2: Ulevostinag Area Under the Plasma Drug Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
The AUC0-24 is a measure of the amount of drug in the blood over time for 0 hours to 24 hours. The AUC0-24 of ulevostinag administered via IT injection as monotherapy and the AUC0-24 of ulevostinag administered via IT injection as combination therapy with pembrolizumab IV infusion were evaluated.
Measured: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Ulevostinag Minimum Plasma Concentration (Cmin)
Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. The Cmin of ulevostinag administered via IT injection as monotherapy and the Cmin of ulevostinag administered via IT injection as combination therapy with pembrolizumab IV infusion were evaluated.
Measured: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose; Cycle 2 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, and 6 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Ulevostinag Maximum Plasma Concentration (Cmax)
Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. The Cmax of ulevostinag administered via IT injection as monotherapy and the Cmax of ulevostinag administered via IT injection as combination therapy with pembrolizumab IV infusion were evaluated.
Measured: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose; Cycle 2 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, and 6 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Pembrolizumab Minimum Plasma Concentration (Cmin)
Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. The Cmin of pembrolizumab IV infusion in combination with MK-1454 administered via IT injection was evaluated.
Measured: Predose on Day 1 of Cycles 1, 2, and 4, and every 4 cycles thereafter up to Cycle 35 (up to 2 years). Each cycle was 21 days.
Parts 1 and 2: Objective Response Rate (ORR) As Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
ORR is defined as the percentage of participants in the analysis population 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, taking as reference the baseline sum diameters) per RECIST 1.1. The ORR of ulevostinag at the preliminary RP2D in combination with pembrolizumab will be assessed by RECIST 1.1 modified to follow a maximum of 10 target lesions with a maximum of 5 target lesions per organ.
Measured: Up to approximately 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2017 (estimated)
- Study start3 Feb 2017
- Primary completion21 Apr 2022
- Study completion21 Apr 2022
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies 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
- 156 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
- NCT03010176
- Sponsor's protocol ID
- 1454-001
- Other IDs
- MK-1454-001, 2016-003160-40, 2016
- Status last verified
- Oct 2025
- First submitted
- 3 Jan 2017
- Last updated
- 29 Oct 2025
- 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
Publications
Harrington KJ, Champiat S, Brody JD, Cho BC, Romano E, Golan T, Hyngstrom JR, Strauss J, Oh DY, Popovtzer A, Gomez-Roca C, Perets R, Kim SB, Wong DJ, Powell SF, Khilnani A, Jemielita T, Zhao Q, Zhao R, Ingham M. Phase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas. Clin Cancer Res. 2025 Aug 14;31(16):3400-3411. doi: 10.1158/1078-0432.CCR-24-3630.
PubMed 40499147Gogoi H, Mansouri S, Jin L. The Age of Cyclic Dinucleotide Vaccine Adjuvants. Vaccines (Basel). 2020 Aug 13;8(3):453. doi: 10.3390/vaccines8030453.
PubMed 32823563
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Open-label, Multicenter Study of MK-1454 Administered by Intratumoral Injection as Monotherapy and in Combination With Pembrolizumab for Patients With Advanced/Metastatic Solid Tumors or Lymphomas
- ClinicalTrials.gov ID
- NCT03010176
- Acronym / sponsor ID
- 1454-001
- Conditions
- Solid Tumors, Lymphoma
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Intratumoral (IT)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 156 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 3 Feb 2017 (actual)
- Primary completion
- 21 Apr 2022 (actual)
- Study completion
- 21 Apr 2022 (actual)
- First posted
- 4 Jan 2017 (estimated)
- Results
- Posted 26 Feb 2024
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 identify a maximum tolerated dose (MTD) or maximum administered dose (MAD) of ulevostinag alone and of ulevostinag in combination with pembrolizumab in participants with advanced/metastatic solid tumors or lymphomas in Part 1, and to evaluate the safety and efficacy of ulevostinag via intratumoral (IT) injection in combination with pembrolizumab in selected solid tumors in Part 2.
Ulevostinag will be administered IT; pembrolizumab (pembro) will be administered via intravenous (IV) infusion. In Part 1, participants will be allocated to one of three treatment arms: ulevostinag monotherapy (cutaneous/subcutaneous [cut/subcut] lesions), ulevostinag +pembro (cut/subcut lesions), or ulevostinag +pembro (visceral lesions).
In Part 2, participants with head and neck squamous cell carcinoma (HNSCC) who are anti-programmed cell death-protein 1 or anti-programmed cell death-ligand 1 (anti-PD-1/PD-L1) refractory or with anti-PD-1/PD-L1 treatment (TrT)-naïve triple-negative breast cancer (TNBC) or with anti-PD-1/PD-L1 TrT-naïve solid tumors with liver metastases/lesions will receive ulevostinag via IT injection at the preliminary Recommended Phase 2 Dose (RP2D) determined in Part 1 PLUS pembrolizumab via IV infusion for up 35 cycles (up approximately 2 years).
Detailed description
Participants will receive either ulevostinag monotherapy or ulevostinag in combination with pembrolizumab for up to 35 cycles (approximately 2 years). Participants will undergo at least a 24-hour inpatient observation period following the first dose administration of ulevostinag on Cycle 1 Day 1 in Part 1. For Part 2, the length of the observation period following administration of the first dose of ulevostinag on Cycle 1 Day 1 is at least 8 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions) | Experimental | Drug: UlevostinagParticipants with cutaneous (cut) or subcutaneous (subcut) lesions will receive escalating doses of ulevostinag monotherapy via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond for up to 35 cycles (up to approximately 2 years). |
| Part 1 Arm 2: Ulevostinag +Pembro (Cut/Subcut Lesions) | Experimental | Drug: Ulevostinag, Biological: PembrolizumabParticipants with cut or subcut lesions will receive escalating doses of ulevostinag via IT injection on Days 1, 8, and 15 of each 21-day cycle for Cycles 1, 2, and 3 and then on Day 1 of each 21-day cycle for Cycles 4 and beyond PLUS pembrolizumab (pembro) via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions) | Experimental | Drug: Ulevostinag, Biological: PembrolizumabParticipants with visceral lesions will receive escalating dose frequencies of ulevostinag via IT injection at escalating dose frequencies (Day 1 of each 21-day cycle for up to 35 cycles, then Days 1 and 8 of each 21-day cycle for two cycles, then Day 1 of each 21 day cycle up to 35 cycles, then Days 1, 8, and 15 of each 21-day cycle for two cycles followed by Day 1 of each 21-day cycle up to 35 cycles, PLUS pembrolizumab IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (approximately 2 years). |
| Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory | Experimental | Drug: Ulevostinag, Biological: PembrolizumabParticipants with HNSCC who are anti-programmed cell death-1 or anti-programmed cell death-ligand 1 refractory will receive ulevostinag at the preliminary Recommended Phase 2 Dose (RP2D) determined by dose escalation in Part 1 Arm 1 and 2 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC | Experimental | Drug: Ulevostinag, Biological: PembrolizumabParticipants with TNBC who are anti-PD-1/PD-L1 treatment-naïve or who have refractory unresectable locally advanced or metastatic TNBC will receive ulevostinag at the preliminary RP2D determined by dose escalation in Part 1 via IT injection on Days 1, 8, and 15 of Cycles 1 and 2 and on Day 1 of each 21-day cycle from Cycle 3 onward (up to a total of 35 cycles) PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (up to approximately 2 years). |
| Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver | Experimental | Drug: Ulevostinag, Biological: PembrolizumabParticipants with solid tumors with liver metastases/lesions who are anti-PD-1/PD-L1 treatment-naïve will receive ulevostinag at the preliminary RP2D based on Part 1: ulevostinag + pembro (visceral lesions) treatment arm via IT injection in a to-be-determined dose and frequency, based on data from Arm 3, PLUS pembrolizumab via IV infusion on Day 1 of each 21-day cycle for up to 35 cycles (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 (28 listed)
- Has ≥1 injectable lesion which is measurable and amenable to injection and biopsy.
- Has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Demonstrates adequate organ function within 7 days prior to treatment initiation.
- Female participants of childbearing potential must be using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse (on a long-term and persistent basis) during the intervention period and for at least 130 days after the last dose of study intervention and agrees not to donate eggs to others or freeze/store for personal use for the purpose of reproduction during this period. Male participants must agree to refrain from donating sperm PLUS either be abstinent from heterosexual intercourse (on a long-term and persistent basis) OR agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse contraception, unless confirmed to be azoospermic (vasectomized) during the intervention period and for at least 130 days after the last dose of study intervention.
- Human Immunodeficiency (HIV)-infected participants must meet these additional criteria: a) Has laboratory-test-documented HIV-1 infection; b) Has well-controlled HIV on anti-retroviral therapy (ART), defined as: 1) must have a cluster of differentiation (CD4+) T-cell count >350 cells/mm^3 at time of screening; 2) must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 or the lower limit of quantification (LLOQ) using the locally available assay at the time of screening and for ≥12 weeks prior to screening; and, 3) must have been on a stable regimen, without changes in drugs or dose modification, for ≥4 weeks prior to study entry (Day 1).
Key exclusion criteria (27 listed)
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Baseline or Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 from the adverse events due to cancer therapeutics administered >4 weeks earlier.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and has received study therapy or has used an investigational device within 28 days of administration of ulevostinag. Note: Prior exposure to immunotherapeutics is allowed, including PD-1 and PD-L1 inhibitors
- Is expected to require any other form of antineoplastic therapy while on study.
- Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤ 10 mg/day is acceptable), or on any other form of immunosuppressive medication.
- Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 2 years.
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 |
|---|---|---|
| UlevostinagAlso: MK-1454IT injection | Drug | Part 1 Arm 1: Ulevostinag (Cut/Subcut Lesions), Part 1 Arm 2: Ulevostinag +Pembro (Cut/Subcut Lesions), Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions), Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory, Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC, Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver |
| PembrolizumabAlso: MK-3475, Keytruda®IV infusion | Biological | Part 1 Arm 2: Ulevostinag +Pembro (Cut/Subcut Lesions), Part 1 Arm 3: Ulevostinag+Pembro (Visceral Lesions), Part 2 Cohort A: HNSCC Anti-PD-1/PD-L1 Refractory, Part 2 Cohort B: Anti-PD-1/PD-L1 TrT-Naïve or Refractory TNBC, Part 2 Cohort C: Anti-PD-1/PD-L1 TrT-Naïve Solid Tumors-Liver |
Primary outcome
Part 1: Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE 4.0)
Time frame: Cycle 1 (21-day cycle)
DLTs were assessed during the first cycle (21 days) \& are defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia, Gr 3 thrombocytopenia (if associated with clinically significant bleeding); nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention is required, leads to hospitalization, or persists for >1 week); Gr 3 or 4 febrile neutropenia; drug-related toxicity that causes treatment discontinuation or dose delay >7 days between consecutive doses during Cycle 1; drug-related toxicity that causes a >2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is ≥3× upper limit of normal (ULN) \& an elevated total bilirubin value ≥2× ULN \& an alkaline phosphatase value <2× ULN, in which no alternative reasons can be found; ≥Gr 2 immune-mediated uveitis; or Gr 5 toxicity.
Parts 1 and 2: Number of Participants Who Experienced One or More Adverse Events (AEs)
Time frame: Up to approximately 2 years
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
Parts 1 and 2: Number of Participants Who Discontinued Study Drug Due to an AE
Time frame: Up to approximately 2 years
AEs are defined as any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the study treatment, is also an AE.
5 secondary outcomes
Parts 1 and 2: Ulevostinag Area Under the Plasma Drug Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24)
Time frame: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Ulevostinag Minimum Plasma Concentration (Cmin)
Time frame: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose; Cycle 2 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, and 6 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Ulevostinag Maximum Plasma Concentration (Cmax)
Time frame: Cycle 1 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, 6, 12, and 24 hours postdose; Cycle 2 Day 1: Predose, at end of IT injection (up to 15 minutes) and 0.5, 1, 1.5, 4, and 6 hours postdose. Each cycle was 21 days.
Parts 1 and 2: Pembrolizumab Minimum Plasma Concentration (Cmin)
Time frame: Predose on Day 1 of Cycles 1, 2, and 4, and every 4 cycles thereafter up to Cycle 35 (up to 2 years). Each cycle was 21 days.
Parts 1 and 2: Objective Response Rate (ORR) As Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Up to approximately 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40499147Harrington KJ, Champiat S, Brody JD, Cho BC, Romano E, Golan T, Hyngstrom JR, Strauss J, Oh DY, Popovtzer A, Gomez-Roca C, Perets R, Kim SB, Wong DJ, Powell SF, Khilnani A, Jemielita T, Zhao Q, Zhao R, Ingham M. Phase I and II Clinical Studies of the STING Agonist Ulevostinag with and without Pembrolizumab in Participants with Advanced or Metastatic Solid Tumors or Lymphomas. Clin Cancer Res. 2025 Aug 14;31(16):3400-3411. doi: 10.1158/1078-0432.CCR-24-3630.
- Derived from this study: PubMed 32823563Gogoi H, Mansouri S, Jin L. The Age of Cyclic Dinucleotide Vaccine Adjuvants. Vaccines (Basel). 2020 Aug 13;8(3):453. doi: 10.3390/vaccines8030453.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Related trials for Solid Tumors
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm
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
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ulevostinag and Pembrolizumab in people with Solid Tumors and Lymphoma, run by Merck Sharp & Dohme LLC at 19 sites in 5 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 28 inclusion and 27 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 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in United States, France, Israel, South Korea, United Kingdom. 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 26 Feb 2024). 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?
Part 1: Percentage of Participants Who Experienced a Dose-limiting Toxicity (DLT) Per Common Terminology Criteria for Adverse Events, Version 4.0 (CTCAE 4.0) (time frame: Cycle 1 (21-day cycle)). 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?
On the ClinicalTrials.gov record for NCT03010176, which also lists 2 linked publications.
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 29 Oct 2025.