Eligibility Exclusion Criteria
Exclusion Criteria:
Phase 2 - Cohort 1 (only) exclusion criteria:
Subjects have tumors that have actionable genomic alterations with approved targeted therapy in first line setting are not eligible to participate.
Subjects are not eligible if they received any prior therapy (SOC or investigational) for advanced or metastatic disease including chemotherapy, targeted therapy, or immunotherapy of any kind such as the following: pembrolizumab, an anti-PD(L)-1 or anti-programmed death ligand 2 (PD-L2) agent, or an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA4, OX40 (Tumor necrosis factor receptor superfamily, member 4), CD137(Tumor necrosis factor receptor superfamily member 9)).
Undergone prior treatment with a known AXL inhibitor such as bemcentinib (see Section 8.2.2 for full list of AXL inhibitors).
Received prior systemic anticancer therapy within 5 half-lives or 3 weeks, whichever is shorter, prior to starting the first dose of study drug(s). Examples of prior systemic anticancer therapy includes cytotoxic agents, targeted therapy such as small molecules, mAbs and hormonal therapy etc..
Received immunotherapies [including but not limited to PD(L)-1 inhibitors, etc.] within 4 weeks prior to starting the first dose of study drug(s).
Received prior radiotherapy within 2 weeks of the first dose of study drug(s) or 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 following palliative radiation (≤ 2 weeks of radiotherapy) for non-central nervous system (CNS) disease.
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 drug(s).
Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent, follow-up is primarily non-invasive, and the subject can comply with protocol requirements.
Has not recovered to ≤ Grade 1 or to baseline from prior cancer therapy toxicity.
Note: Subject with ≤ Grade 2 neuropathy may be an exception to this criterion and may qualify for the study after discussion with Sponsor. Subjects with endocrine-related AEs ≤ Grade 2 requiring treatment or hormone replacement may be eligible after discussion with Sponsor.
Note: Toxic effects also include laboratory results that have not resolved to ≤ Grade 1. Subjects with ≤ Grade 2 alopecia are an exception to this criterion.
Has not adequately recovered from major surgery and/or complications from the procedure prior to the first dose of study drug(s).
Pulmonary hemorrhage or hemoptysis > 2.5 mL blood within 6 weeks of screening (or within 2 weeks if the source of bleeding is treated).
Received a live or live-attenuated vaccine within 30 days prior to the first dose of study drug(s). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guerin, and typhoid vaccine. Seasonal influenza vaccines are generally killed virus vaccines and are permitted; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live-attenuated vaccines and are not allowed.
Note: The administration of killed vaccines, mRNA vaccines, and DNA vaccines is allowed.
Has an active diagnosis of immunodeficiency or is receiving systemic steroid therapy (exceeding 10 mg daily of prednisone equivalent) or has received any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug(s).
Has active autoimmune disease which required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Note: Hormone therapy (e.g., thyroxine, insulin, or corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
Known additional malignancy that is progressing or has required active treatment within the past 2 years.
Note: Subjects with curatively treated basal or squamous cell carcinoma of the skin (non-melanoma skin cancer), cervical or vaginal intra-epithelial neoplasia, non-invasive breast cancer in situ, or localized prostate cancer with a prostate-specific antigen level of 2-year disease-free interval and whose natural history or treatment does not have the potential to interfere with investigational agents (e.g., hormone maintenance) may be enrolled after approval by the Medical Monitor/Sponsor.
Known active CNS metastases and/or carcinomatous meningitis. Subjects with adequately treated brain metastases may participate provided they meet the following criteria:
Are radiologically stable (no progression) for at least 4 weeks as documented by screening computed tomography (CT) or magnetic resonance imaging (MRI) scan.
Clinically stable.
No evidence of new or enlarging brain metastases. Does not require steroids for at least 14 days before starting first dose of study drug(s) (anticonvulsants at a stable dose are allowed). Low dose steroids equivalent of prednisone ≤ 10 mg orally once a day is allowed.
No history of intracranial or spinal cord hemorrhage.
No evidence of significant vasogenic edema.
Severe hypersensitivity (≥ Grade 3) to pembrolizumab or SLC-391 and/or any excipients.
A history of non-infectious pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
A known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies). No HIV testing is required unless mandated by the local health authority.
Known history of Hepatitis B (Anti-HBc and HBsAg reactive) or known active Hepatitis C virus (RNA, qualitative) infection.
Note: No testing for Hepatitis B or C is required unless mandated by a local health authority.
A history or current evidence of any severe acute or chronic medical or psychiatric condition that requires treatment, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject, in the opinion of the Principal Investigator (PI; also referred to as Investigator). Examples include, but are not limited to, active uncontrolled infection (including tuberculosis [TB]) requiring systemic therapy, transfusion dependent anemia, recent (within 90 days) stroke or myocardial infarction, unstable angina, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, symptomatic congestive heart failure (New York Heart Association class ≥ III/IV), and recent severe COVID-19.
Note: TB testing is required for subjects recently exposed to persons with active TB or who have traveled recently to areas where TB is endemic.
Systolic blood pressure (BP) ≥ 160 mmHg or diastolic BP ≥100 mmHg.
Has a corrected QT interval (QTcF) ≥ 470 msec. Note: Apply the Fridericia QT correction to calculate QTcF using the following formula: QTcF = QT/RR1/3 where QT = the time between the start of the QRS complex and the end of the T wave and RR = the time between the start of one QRS complex and the start of the next QRS complex.
Note: If a subject has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker as deemed by the Investigator (i.e., the subject otherwise has no cardiac abnormalities), the subject may be eligible to participate in the study following discussion with the Sponsor.
History or presence of sustained or symptomatic bradycardia (≤ 55 bpm), left bundle branch block, ventricular arrhythmia excluding premature ventricular contractions, or uncontrolled ventricular arrhythmia. Subjects with a supraventricular arrhythmia requiring medical treatment and a normal ventricular rate are eligible.
Psychological, familial, sociological, or geographical conditions including known psychiatric or substance abuse disorder that could interfere with the subject's ability to provide informed consent, comply with the protocol, or interfere with the interpretation of the study results.
Inability to swallow oral medication and/or the presence of active gastrointestinal (GI) disease and/or other GI conditions, including bowel resection, that is expected to interfere significantly with the absorption, distribution, metabolism, or excretion of oral SLC-391 therapy.
Received radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study drug(s).
Had an allogenic tissue, marrow, or solid organ transplant.
Females who are pregnant or nursing. Note: SLC reserves the right to deny any subject enrollment based upon potential safety concern(s) or factors that could confound the study results.
Note: The Investigator or licensed, medically qualified Sub-Investigator must review and confirm eligibility prior to the first dose of study drug(s).
