Study of MK-1454 Alone or in Combination With Pembrolizumab in Participants With Advanced / Metastatic Solid Tumors or Lymphomas (MK-1454-001)
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).
- 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 lymphomas).
- 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 drug 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) Arms:
- 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, All Cohorts:
- In participants to be treated by liver IT injection, has metastatic liver involvement that does not exceed one third of the total liver volume.
- 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. 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: 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 lesion.
- 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 therapy.
- 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 tumors
- 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.
- 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 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 (SCCHN) 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. MK-1454, ADU-S100).
- 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 allowed.
- Part 2: Solid Tumors with Liver Metastases/Lesions Cohort
- Participants with MSI-H CRC are excluded.
- Part 2: Expansion Cohorts
- Has a history of interstitial lung disease.
Locations & Contacts
Contact: Sa-Heim Davis
Contact: UCSF Clinical Trials
Name Not Available
Name Not Available
Salt Lake City
Name Not Available
Trial Objectives and Outline
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 observation period following the first dose administration of MK-1454 on Cycle 1, Day 1.
Trial Phase & Type
Merck and Company Inc
Secondary IDs NCI-2017-00280, 2016-003160-40, MK-1454-001
Clinicaltrials.gov ID NCT03010176