The purpose of this study is to identify a maximum tolerated dose (MTD) or maximum
administered dose (MAD) of MK-1454 alone and of MK-1454 in combination with pembrolizumab
(MK-3475) in participants with advanced/metastatic solid tumors or lymphomas in Part 1, and
to evaluate the safety and efficacy of MK-1454 via intratumoral (IT) injection in combination
with pembrolizumab in selected solid tumors in Part 2.
MK-1454 will be administered IT; pembrolizumab (pembro) will be administered via intravenous
(IV) infuison. In Part 1, participants will be allocated to one of three treatment arms:
MK-1454 monotherapy (cutaneous/subcutaneous [cut/subcut] lesions), MK-1454+pembro (cut/subcut
lesions), or MK-1454+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-naïve triple-negative breast cancer (TNBC) or
with anti-PD-1/PD-L1 treatment-naïve solid tumors with liver metastases/lesions will receive
MK-1454 via IT injection at the RP2D determined in Part 1 PLUS pembrolizumab via IV infusion
for up 35 cycles (up approximately 2 years).
Participants will receive either MK-1454 monotherapy or MK-1454 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 MK-1454 on
Cycle 1 Day 1 in Part 1. For Part 2, with Protocol Amendment 06 (dated 23 Aug 2019), the
length of the observation period following administration of the first dose of MK-1454 on
Cycle 1 Day 1 is at least 8 hours.
- All Arms and Cohorts (Parts 1 and 2):
- Has ≥1 injectable lesion which is measurable and amenable to injection and biopsy.
- 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
- 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 willing to use a highly
effective method of birth control or be surgically sterile, or abstain from
heterosexual activity for the course of the study through 130 days after last dose of
study treatment. Male participants of reproductive potential must agree to use a
highly effective method of contraception during sexual contact with females of
childbearing potential starting with the first dose of study treatment through 130
days after the last dose of study treatment.
- 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).
- Part 1, MK-1454 (cut/subcut lesions) and Part 1, MK-1454+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, MK-1454+pembro (visceral lesions) Arm:
- 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.
- Part 2: HNSCC Cohort:
- 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.
- 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
- Part 2: TNBC Cohort:
- Has confirmed 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
- Has received either 1 or 2 prior systemic treatments for metastatic breast cancer and
has intolerance to, or documented disease progression on or after their most recent
- Has been previously treated with an anthracycline and/or taxane in the (neo)adjuvant
or metastatic setting.
- Part 2: Solid tumors with liver metastases including pancreatic cancer,
non-microsatellite instability-high (MSI-H) colorectal cancer CRC, and other solid
- Has histologically or cytologically confirmed Stage IV solid tumor that is not
- 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.
- 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 MK-1454. 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.
- Has clinically active central nervous system metastases and/or carcinomatous
- 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
- Has a history of vasculitis.
- Has an active infection requiring therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or current
- Has undergone prior allogeneic hematopoietic stem cell transplantation within the last
- 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
- 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
- HIV-infected participants who have had an HIV-related opportunistic infection within 6
- Has been treated with a Stimulator of Interferon Genes (STING) agonist (e.g. MK-1454,
- Part 2:
- 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
- For Cohort C, participants with MSI-H CRC are excluded.
- Has a history of interstitial lung disease.