ENB003 Plus Pembrolizumab Phase 1b/2a in Solid Tumors

Exclusion Criteria

Pregnancy Exclusion

• A WOCBP who has a positive urine pregnancy test (e.g. within 72 hours) prior to treatment. If the urine test is positive or cannot be confirmed as negative, a negative serum pregnancy test will be required.
• Is breastfeeding or expecting to conceive or father children within the projected duration of the study, from the day date of informed consent through to 150 days after the last dose of study treatment for females, and 120 days after the last dose of study treatment for males.

Prior/Concomitant Therapy

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whichever is shorter, prior to treatment.

Note: Subjects must have recovered from all AEs due to previous therapies to ≤Grade 1 severity or baseline. Subjects with ≤Grade 2 neuropathy may be eligible at Investigator's discretion. Subjects with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.

Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the surgery prior to starting study treatment, as determined by the Investigator.

• Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Note: Subjects must have recovered from all radiation-related toxicities, and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

Prior/Concurrent Clinical Study Experience

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Note: Subjects who have entered the follow-up phase of an investigational study may participate provided it has been 4 weeks after the last dose of the previous investigational agent.

Diagnostic Assessments

• Average Fridericia-corrected QT interval (QTcF) >460 msec for males and QTcF >480 msec for females as measured by electrocardiogram (ECG) at Screening.
• A family history of congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Subjects with basal cell carcinoma of the skin, SCC of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.

• Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Has severe hypersensitivity (≥ Grade 3) to ENB-003 and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Subjects with known human immunodeficiency virus (HIV), active HBV or active HCV infections. Subjects who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to starting treatment (Note: Subjects should remain on HBV antiviral therapy throughout the study and follow local guidelines for HBV anti-viral therapy post completion of the study intervention).

Subjects with a history of HCV infection are eligible if HCV viral load is undetectable at screening (Note: must have completed curative anti-viral therapy at least 4 weeks prior to starting treatment).

• Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
• Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.
• History of myocardial infarction ≤ 6 months prior to Screening, or uncontrolled congestive heart failure or uncontrolled atrial fibrillation or uncontrolled ventricular arrythmia.
• Has a history of Pulmonary Arterial Hypertension or Renovascular Hypertension
• Blood pressure ≥ (greater than or equal to)150/90 mm Hg.

Other Exclusions

• Has had an allogenic tissue/solid organ transplant.
• Has previously participated in this protocol [ENB-003-101 (MK3475-951)] i.e. a subject previously enrolled in Part A cannot participate in Part B.