JSI-1187-01 Monotherapy and in Combination With Dabrafenib for Advanced Solid Tumors With MAPK Pathway Mutations

Inclusion Criteria: * Males and females ≥ 18 years of age * Have locally advanced or metastatic solid tumor malignancy with measurable disease and be an appropriate candidate for experimental therapy * Part A (JSI-1187 Monotherapy Dose Escalation): Histologically or cytologically confirmed MAPK pathway mutation, including hyperactivating pathway mutations or gene fusions, e.g., BRAF (Class I, II or III), RAS (H/K/N), MEK (MAP2K1), RAS-GAP (NF1 loss, RASA1), RAS-GEF, refractory to or relapsed on prior therapy, and have received all available therapy known to confer clinical benefit * (On hold, effective 05 July 2023) Part B (JSI-1187 Plus Dabrafenib Combination Dose Escalation): Histologically or cytologically confirmed BRAF V600E/K-mutated unresectable or metastatic melanoma, BRAF V600E-mutated metastatic NSCLC, BRAF V600E-mutated locally advanced or metastatic anaplastic thyroid cancer, or other BRAF V600E-mutated unresectable or metastatic solid tumors, refractory to, or relapsed on, prior therapy, and have received all available therapy known to confer clinical benefit * (On hold, effective 05 July 2023) Part C (JSI-1187 Plus Dabrafenib Expansion Cohorts): Histologically or cytologically confirmed: * Cohort 1: BRAF V600E/K-mutated unresectable or metastatic melanoma after 1-3 prior therapies for metastatic disease, including anti-PD1 therapy, with or without ipilimumab, and BRAF/MEK inhibitor treatment * Cohort 2: BRAF V600E/K-mutated unresectable or metastatic melanoma after BRAF/MEK inhibitor adjuvant therapy for Stage 3 disease followed by 1-2 prior therapies for metastatic disease, including anti-PD-1 therapy, with or without ipilimumab, and excluding BRAF/MEK inhibitor treatment * Cohort 3: BRAF V600E-mutated metastatic NSCLC after 1 or 2 prior therapies for metastatic disease * MAPK mutation tumor status will be established prior to entry based on previous MAPK pathway mutation reports from a CLIA qualified laboratory, or, if a report is not available, the mutation analysis will be performed at Screening on archival tissue or newly biopsied tumor tissue. * Have discontinued previous treatments for cancer and have resolution, except where otherwise stated in the inclusion criteria, of all clinically significant toxic effects of prior cancer treatment, surgery, or radiotherapy to Grade ≤ 1. Subjects with prior immune checkpoint inhibitor endocrinopathies must have resolution to ≤ Grade 2 and be stable on hormonal therapy (e.g., levothyroxine, hydrocortisone, insulin, etc.). * Adequate performance status: Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Life expectancy of ≥ 3 months * Subjects with asymptomatic stable, prior or currently treated brain metastases are allowed * Adequate hematologic parameters without ongoing transfusional support: * Hemoglobin (Hb) ≥ 9 g/dL * Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9 cells/L * Platelets ≥ 75 x 10\^9 cells/L * Adequate renal and hepatic function: * Creatinine ≤ 1.5 times the upper limit of normal (ULN), or calculated creatinine clearance ≥ 50 mL/minute x 1.73 m\^2 per the Cockcroft-Gault formula * Total bilirubin ≤ 1.5 times the (ULN) unless due to Gilbert's disease * ALT/AST ≤ 2 times the ULN, or \< 3 times the ULN for subjects with liver metastases * Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after the completion of study treatment. * Ability to provide written informed consent Exclusion Criteria: * Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV * QT interval corrected for rate (QTc) \> 480 msec on the ECG obtained at Screening using Fridericia method for QTc calculation * Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for patient care. * Medications that are strong inhibitors of CYP3A4 are prohibited during study and for 14 days prior to the first dose of study drug(s). * Medications that are strong inducers of CYP3A4 are prohibited during study and for 14 days prior to the first dose of study drug(s). * Medications that are strong inhibitors of BCRP are prohibited during study and for 14 days prior to the first dose of study drugs(s). * Subjects on dabrafenib (Parts B and C) also are advised to avoid concurrent administration of strong inhibitors of CYP2C8 as these medications may increase the concentration of dabrafenib * History of or current evidence/risk of retinal vein occlusion or central serous retinopathy, or has medically relevant abnormalities identified on screening ophthalmologic examination * Symptomatic central nervous system malignancy or metastasis * Gastrointestinal conditions that could impair absorption of study drug(s) * Current hematologic malignancies * Second, active primary solid tumor malignancy that, in the judgement of the investigator or Sponsor medical monitor, may affect the interpretation of results * Prior malignancies, with the exception of carcinoma in situ of any origin, non-muscle invasive bladder cancer, Gleason 3+3 prostate cancer and prior malignancies in remission whose likelihood of recurrence is very low, as judged by the Sponsor medical monitor. * Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment within the last week prior to study treatment * Other active infection requiring IV antibiotic usage within the last week prior to study treatment * Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results * Receipt of an investigational product on a clinical trial within 5 elimination half-lives or within 28 days, whichever is shorter, prior to C1D1 on this study, or currently enrolled in a clinical trial, involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study * Previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor. * If female, pregnant, breast-feeding, or planning to become pregnant