GSK PRMT1: This phase I trial is trying to find the most suitable dose of an oral drug (GSK3368715) in patients who have a solid cancer type or a Diffuse Large B-Cell LymphomaA Phase I, Open-label, Dose-escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3368715 in Participants With Solid Tumors and DLBCL

Inclusion

• Participant must be >=18 to years of age inclusive, at the time of signing the informed consent.
• Diagnosis of one of the following; Part 1 (Dose Escalation and food effect): Histologically- or cytological-confirmed diagnosis of solid tumor malignancy that is metastatic or non-resectable; have received all standard treatment options or are no longer eligible for additional standard treatment options. Evaluable disease that may be measured directly by the size of the tumor or can be evaluated by other methods. Availability of a biopsy of the tumor tissue obtained at any time from the initial diagnosis to study entry. Although a fresh biopsy, which is obtained during screening, is preferred, archival tumor specimen is acceptable if it is not feasible to obtain a fresh biopsy. For participants in the PK/PD cohort, a fresh biopsy and consent for one on treatment biopsy are required for enrollment. Part 2 (Dose Expansion): Cohort 2A & 2B: The availability of archival tumor tissue, or willingness to undergo a fresh biopsy to determine MTAP status (any archival tumor specimen must have been obtained within 6 months prior to starting study drug unless approved by the study Medical Monitor). Local MTAP or Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) results are acceptable for enrollment, but must be confirmed through central laboratory testing. Cohort 2A: Histologically- or cytological-confirmed diagnosis of DLBCL; relapse or refractory disease after at least 1 but not more than 4 lines of prior therapy; at least 1 measurable site of disease according to the Lugano Classification. The site of disease must be greater than 1.5 centimeter (cm) in the long axis regardless of short axis measurement or greater than 1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions. Cohort 2B: Pancreatic Cancer: Histologically or cytologically confirmed adenocarcinoma of the pancreas; unresectable, locally advanced (Stage III), or metastatic (Stage IV) disease; relapsed or refractory disease after at least 1 prior line of approved, systemic therapy; at least 1 measurable tumor lesion per RECIST 1.1. NSCLC: histologically or cytologically confirmed NSCLC; stage IV disease; tested for presence of echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) rearrangement; received at least 2 prior lines of approved, systemic therapy, of which 1 therapy has to be a platinum containing regimen or failed a first-line platinum-containing regimen in combination with an anti- progressive disease (PD1) monocloncal antibody and refused a second-line regimen despite being informed about the different therapeutic options and their specific clinical benefit by the investigator; the content of this informed consent discussion including the therapeutic options reviewed by the investigator need to be documented and the participant needs to sign a specific consent form; at least 1 measurable tumor lesion per RECIST 1.1. Transitional cell carcinoma of the Urothelium: histologically or cytologically confirmed transitional cell carcinoma (TCC) of the urothelium (urinary bladder, urethra, ureter or renal pelvis) including mixed pathology with predominantly (that is [i.e.], > 50 percent of the histopathology sample) TCC with the exception of neuroendocrine or small cell carcinoma; unresectable, locally advanced (T4b) or metastatic (lymph node or visceral) disease; relapsed or refractory disease after at least 1 prior line of approved systemic therapy; at least 1 measurable tumor lesion per RECIST 1.1.
• Adequate organ function as defined by: Absolute neutrophil count (ANC) with a laboratory value of >=1.5 times 10^9 per liter (L); Hemoglobin with a laboratory value of >=9 grams per deciliter (g/dL) for solid malignancy and >=8 g/dL for Non-Hodgkin's lymphoma; Platelets with a laboratory value of >=100 times 10^9/ L; prothrombin time/ International Normalization Ratio (PT/INR) and partial thromboplastin time (PTT) with a laboratory value of <=1.5 times upper limit of normal (ULN), unless participant is receiving systemic anticoagulation (Hematologic); Albumin with a laboratory value of >=2 g/dL, total bilirubin with a laboratory value of <=1.5 times ULN, alanine aminotransferase (ALT) with a laboratory value of <=2.5 times ULN (Part 1 and 2) or <5 times ULN (Part 2 only) is acceptable for participants with documented liver metastases/tumor infiltration (Hepatic); calculated creatinine clearance by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or measured from 24 h urine with a laboratory value of >= 50 milliliters per min (mL/min) (Renal); Ejection fraction with a laboratory value of >=Lower limit of normal (LLN) by echocardiogram (minimum of 50 percent)/ multigated (radionuclide) angiogram (MUGA), Electrocardiogram (ECG): corrected QT (QTc) interval using Fridericia's formula (QTcF) with a laboratory value of <450 milliseconds (msec) (Cardiac).
• Eastern cooperative oncology group (ECOG) performance status of 0 or 1.
• Able to swallow and retain orally-administered medication.
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies; is not a woman of childbearing potential (WOCBP) or is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1 percent, during the intervention period and for at least 120 days, corresponding to the time needed to eliminate any study intervention(s) (example given [e.g.], 5 terminal half-lives) after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine as required by local regulations) within 7 days before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 100 days, corresponding to time needed to eliminate study intervention(s) (e.g., 5 terminal half-lives) plus 90 days after the last dose of study intervention: Refrain from donating sperm plus either: Be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier as detailed below; agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant; agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person.
• Capable of giving signed informed consent.