MC# 17-24 - A Phase I Open-label, Multicenter Study of MK-2118 Administered by Intratumoral Injection as Monotherapy and in Combination with Pembrolizumab for Patients with Advanced/Metastatic Solid Tumors or Lymphomas

  • Agent(s): MK-2118
  • Disease Type(s): Bladder, Breast, Cervical, Colorectal, Endometrial, Esophageal, Gastric, Head and Neck, Hepatocellular, Lung-NSCLC, Lung-SCLC, Lymphoma, Melanoma, Mesothelioma, Neuroendocrine, Ovarian, Pancreatic, Prostate, Renal, Sarcoma, Solid Tumor, Squamous Cell, Thyroid, Cholangiocarcinoma
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Small Molecule
  • Molecular Target(s): STING

Mechanism of Action

MK-2118 is a novel small molecule that is an agonist of the intracellular innate immune adaptor, Stimulator of Interferon Genes (STING), which, when activated, induces Type I interferons and other pro-inflammatory cytokines that potentiate T-cell activation.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much MK-2118 can be given alone or in combination with Pembrolizumab with an acceptable level of side effects
  • The effects of MK-2118 when given alone or in combination with Pembrolizumab
  • How much MK-2118 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  • Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit. Solid tumors and lymphomas of any type are eligible for enrollment. Tumor types of greatest interest include, but are not limited to, malignant melanoma, head and neck squamous cell carcinoma, breast adenocarcinoma, and lymphomas.
  • Have stage III or stage IV disease that is not surgically resectable.
  • Have at least 1 injectable lesion that is amenable to injection and biopsy via visual inspection for a cutaneous lesion, or via ultrasound guidance for a subcutaneous lesion. This injectable lesion must be measurable, as defined below:
    • A cutaneous or subcutaneous lesion ≥ 1 cm in longest diameter for solid tumors, or ≥ 1.5 cm in short axis for a nodal lesion in participants with solid tumor. The longest diameter for an injectable lesion must be ≤ 10 cm for both solid tumors and nodal lesions in participants with solid tumor.
  • Multiple coalescing, superficial lesions that in aggregate have a longest diameter of ≥ 1 cm and ≤ 10 cm.
  • For lymphoma, a nodal lesion ≥ 1.5 cm in short axis, or an extra-nodal lesion ≥ 1 cm in 2 dimensions. Nodal lesions ≥ 1.0 cm and < 1.5 cm in the short axis may be injected, if involvement by lymphoma has been documented by pathology report. The longest diameter for an injectable lesion must be ≤ 10 cm.
  • Have at least 1 discrete, distant noninjected lesion that is amenable to biopsy via visual inspection or amenable to biopsy via image guidance. This lesion must be measurable as defined by the response criteria used to assess the participant (RECIST 1.1 for solid tumors or revised IWG criteria for lymphom as).
    • For RECIST 1.1, ≥ 1 cm in longest diameter for non-nodal lesions, or ≥ 1.5 cm in the short axis for nodal lesions.
  • For revised IWG, a nodal lesion > 1.5 cm in longest diameter or > 1.0 cm in short axis, or an extra-nodal lesion ≥ 1 cm in 2 dimensions.
  • Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Be ≥18 years of age on day of signing informed consent.
  • Male participants:
    • A male participant must agree to use a contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatments (pembrolizumab or MK-2118), after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants:
    • A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies
      • Not a woman of childbearing potential (WOCBP) as defined in Appendix 5
      • A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 120 days after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the trial. The participant may also provide consent/assent for FBR. However, the participant may consent to the main trial without participating in FBR.
  • In order to be eligible for crossover into Arm 2 of this trial, the participant must:
    • Have either clinical or radiographic disease progression on Arm 1 MK-2118 monotherapy.
    • Have completed the DLT evaluation period (21 days of treatment within Cycle 1) in Arm 1 MK-2118 monotherapy.
    • Have at least 1 injectable lesion that is amenable to injection and biopsy via visual inspection for a cutaneous lesion, or via ultrasound guidance for a subcutaneous lesion. This injectable lesion must be measurable, as defined by:
      • A cutaneous or subcutaneous lesion ≥ 1 cm in longest diameter for solid tumors, or ≥ 1.5 cm in short axis for a nodal lesion in solid tumor participants. The longest diameter for an injectable lesion must be ≤ 10 cm for both solid tumors and nodal lesions in solid tumor participants.
    • Multiple coalescing, superficial lesions that in aggregate have a longest diameter of ≥ 1 cm and ≤ 10 cm.
    • For lymphoma, a nodal lesion ≥ 1.5 cm in short axis, or an extra-nodal lesion ≥ 1 cm in 2 dimensions. Nodal lesions ≥ 1.0 cm and < 1.5 cm in the short axis may be injected, if involvement by lymphoma has been documented by pathology report. The longest diameter for an injectable lesion must be ≤ 10 cm.
    • Have at least 1 discrete, distant noninjected lesion that is amenable to biopsy via visual inspection or amenable to biopsy via image guidance. This lesion must be measurable as defined by the response criteria used to assess the participant (RECIST 1.1 for solid tumors or IWG revised criteria for lymphomas).
      • For RECIST 1.1, ≥ 1 cm in longest diameter for non-nodal lesions, or ≥ 1.5 cm in the short axis for nodal lesions.
  • For revised IWG, a nodal lesion > 1.5 cm in longest diameter or > 1.0 cm in short axis, or an extra-nodal lesion ≥ 1 cm in 2 dimensions.
  • Have an ECOG Performance Status of 0 or 1.
  • Demonstrate adequate organ function as defined by Table 3. All screening labs should be performed within the Screening period.
  • A male participant must agree to use a contraceptive method as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
  • A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least 1 of the following conditions applies:
    • Not a WOCBP as defined in Appendix 5
    • A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 120 days after the last dose of study treatment.
  • Demonstrate adequate organ function as defined by the following table (Table 3). All screening labs should be performed within the Screening period.
Exclusion Criteria
  • Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, or in situ cervical cancer.
  • Has clinically active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic (without evidence of progression by magnetic resonance imaging [MRI] scan of the brain separated by at least 4 weeks after treatment), have no evidence of new or enlarging brain metastases, are evaluated within 4 weeks prior to first study drug administration, and are off immunosuppressive doses of systemic steroids at least 2 weeks from enrollment.
  • 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 (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment.
  • Has a history of vasculitis.
  • Has an active infection requiring therapy.
  • Has a known history of active TB (Bacillus tuberculosis).
  • Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
  • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. Note: Participants who have had a stem cell transplant greater than 5 years ago are eligible as long as there are no symptoms of graft-versus-host disease (GVHD).
  • Participants with known human immunodeficiency virus (HIV) and/or Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s compliance for the full duration of the study, would make administration of the study drugs hazardous or make it difficult to monitor adverse effects such that it is not in the best interest of the participant to be enrolled, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere in cooperation with the requirements of the trial.
  • 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. Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study drug administration and participants should be recovered.
  • Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to baseline or CTCAE Grade 1 (Grade 2 alopecia is allowed) from the AEs due to cancer therapeutics administered more than 4 weeks earlier.
  • Has been treated within 2 weeks of Cycle 1 Day1 with any of the following:
    • strong/moderate CYP2C9 inhibitors, such as: amiodarone, felbamate, fluconazole, miconazole, piperine, oxandrolone, fluorouracil and its derivatives (TS-1, UFT, tegafur, carmofur, doxifluridine, capecitabine), sulfaphenazole, cyclosporine, bucurol, tienilic acid.
    • UGT1A3 inhibitors, which include ritonavir, quinidine, probenecid, and valproic acid
    • Strong carbonyl reductase (CBR) inhibitors, which include quercetin, menadione, glycyrrhetinic acid, and flufenamic acid.
  • 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-2118. Note:  Prior exposure to immunotherapeutics is allowed, including PD-1 and PD-L1 inhibitors, provided participant did not experience ≥ Grade 3 drug-related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor.
  • 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. Note: The use of physiologic replacement doses of corticosteroids may be approved after consultation with the Sponsor Medical Monitor or designee.
  • Has received a live vaccine within 28 days prior to first dose.
  • Has been treated with a STING agonist (eg, MK-1454, ADU-S100).
  • Has clinically active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic (without evidence of progression by MRI scan of the brain separated by at least 4 weeks after treatment), have no evidence of new or enlarging brain metastases, are evaluated within 4 weeks prior to first study drug administration, and are off immunosuppressive doses of systemic steroids at least 2 weeks from enrollment.
  • Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody.
  • Has an active infection requiring therapy.
  • Has a known history of active TB (Bacillus tuberculosis).
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s compliance for the full duration of the study, would make administration of the study drugs hazardous or make it difficult to monitor adverse effects such that it is not in the best interest of the participant to be enrolled, in the opinion of the treating investigator.
  • 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 be free of significant detectable infection. Surgeries that required general anesthesia must be completed at least 2 weeks before first study drug administration. Surgery requiring regional/epidural anesthesia must be completed at least 72 hours before first study drug administration and participants should be recovered.
  • Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to baseline or CTCAE grade 1 (Grade 2 alopecia is allowed) from the AEs due to cancer therapeutics administered more than 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-2118. Note: Prior exposure to MK-2118 is allowed, provided the participant has a washout period of at least 14 days and did not experience ≥ Grade 3 drug-related toxicity. Note: Prior exposure to immunotherapeutics is allowed, including PD-1 and PD-L1 inhibitors, provided participant did not experience a ≥ Grade 3 drug- related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor
  • 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.
  • Note: The use of physiologic replacement doses of corticosteroids may be approved after consultation with the Sponsor Medical Monitor.
  • Has been treated within 2 weeks of Cycle 1 Day1 with any of the following:
    • strong/moderate CYP2C9 inhibitors, such as: amiodarone, felbamate, fluconazole, miconazole, piperine, oxandrolone, fluorouracil and its derivatives (TS-1, UFT, tegafur, carmofur, doxifluridine, capecitabine), sulfaphenazole, cyclosporine, bucurol, tienilic acid.
    • UGT1A3 inhibitors, which include ritonavir, quinidine, probenecid, and valproic acid
    • Strong CBR inhibitors, which include quercetin, menadione, glycyrrhetinic acid, and flufenamic acid.
  • Has received a live vaccine within 28 days prior to first dose.
  • Has been treated with a STING agonist (eg, MK-1454, ADU-S100).

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City

Contact Us About This Trial

Reach out to us by sharing your info in the form below or give us a call at 972-566-3000.

Re: MC# 17-24