COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03666988




Registration number
NCT03666988
Ethics application status
Date submitted
10/09/2018
Date registered
12/09/2018
Date last updated
21/08/2020

Titles & IDs
Public title
First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)
Scientific title
A 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
Secondary ID [1] 0 0
2018-001629-20
Secondary ID [2] 0 0
207675
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK3368715
Treatment: Drugs - GSK3368715

Experimental: Part 1: GSK3368715 dose escalation - Eligible participants with solid relapsed/refractory tumors will receive escalating doses of GSK3368715 at a starting dose of 50 mg, administered orally once daily.

Experimental: Part 1: GSK3368715 PK/PD/Metabolite/Biomarker - Additional participants in Part 1, treated at or close to the expected the maximum tolerated dose (MTD)/RP2D, will be evaluated for metabolic and biomarker profiling. Participants may be enrolled into this cohort(s) even after MTD/RP2D has been identified and Part 2 has been initiated.

Experimental: Part 1: GSK3368715 Food effect - Eligible participants will receive single dose of GSK3368715 at starting dose of 50 mg tablet orally in fasted state followed by fed state in Period 1 and Fed followed by fasted state in Period 2.

Experimental: Part 2:GSK3368715 dose expansion - DLBCL participants - Eligible participants with relapsed/refractory DLBCL will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.

Experimental: Part 2:GSK3368715 dose expansion-solid tumor participants - Eligible participants with relapsed/refractory solid tumors (pancreas cancer, NSCLC, and bladder cancer) will receive RP2D of GSK3368715 established during Part 1, administered orally once daily.


Treatment: Drugs: GSK3368715
GSK3368715 will be available with dosing strengths of 25 mg, 100 mg and 250 mg to be administered once daily as an oral capsule.

Treatment: Drugs: GSK3368715
GSK3368715 will be available in Immediate release (IR) white film coated tablet with dosing strengths of 50 mg, 100 mg and 250 mg to be administered orally once daily .

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of participants with dose limiting toxicity (DLT) - An adverse event (AE) is considered to be a DLT if the event is considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to the study intervention during the DLT window (first 21 days of intervention, except for Venous thromboembolism (VTE)) and meets DLT criteria for non-hematologic and hematologic Toxicities.
Timepoint [1] 0 0
Up to 21 days
Primary outcome [2] 0 0
Part 1: Number of participants with AEs and serious AEs (SAEs) - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as serious adverse event (SAE).
Timepoint [2] 0 0
Up to 3.9 years
Primary outcome [3] 0 0
Part 1: Number of participants with AEs by maximum grade - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AEs will be graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (V5.0).
Timepoint [3] 0 0
Up to 3.9 years
Primary outcome [4] 0 0
Part 2: Objective response rate (ORR) - ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR). Participants with solid tumor will be assessed per Response Criteria for Solid Tumors (RECIST) 1.1 and DLBCL participants will be assessed per Lugano Criteria.
Timepoint [4] 0 0
Up to 3.9 years
Secondary outcome [1] 0 0
Part 1: Best overall response - The best overall response is the best response recorded from the start of the intervention until disease progression/initiation of new anti-cancer therapy and will be determined based on the investigators assessment of response at each time point.
Timepoint [1] 0 0
Up to 3.9 years
Secondary outcome [2] 0 0
Part 1: Maximum observed plasma concentration (Cmax) following administration of GSK3368715 - Cmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [2] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose (Day1) of each cycle; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [3] 0 0
Part 1: Time to reach Cmax (Tmax) following administration of GSK3368715 - Tmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [3] 0 0
Pre-dose,15,30 min, 1,1.5,2,3,4,6,8,12,24,48,72 h post-dose (Day1) of each cycle; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [4] 0 0
Part 1: Area under the concentration time curve from time zero to last time of quantifiable concentration (AUC [0-t]) following administration of GSK3368715 - AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [4] 0 0
Pre-dose,15,30 min, 1,1.5,2,3,4,6,8,12,24,48,72 h post-dose (Day1) of each cycle; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [5] 0 0
Part 1: AUC from time zero extrapolated to infinite time (AUC [0-infinity]) following single dose administration of GSK3368715 - AUC(0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [5] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle (Each cycle will be of 21 days)
Secondary outcome [6] 0 0
Part 1: Area under the concentration-time curve over the dosing interval (AUC [0-tau]) following repeat dose administration of GSK3368715 - AUC(0-tau) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [6] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle;Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [7] 0 0
Part 1: Trough concentration (Ctau) following repeat dose administration of GSK3368715 - Ctau of GSK3368715 is to be derived from the PK samples collected.
Timepoint [7] 0 0
Pre-dose on Day 8 and Day 15;Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [8] 0 0
Part 1: Time invariance ratio following administration of GSK3368715 - Time invariance ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Timepoint [8] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Secondary outcome [9] 0 0
Part 1: Accumulation ratio following administration of GSK3368715 - Accumulation ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Timepoint [9] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Secondary outcome [10] 0 0
Part 1: Cmax following administration of GSK3368715 in Fed state - Cmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [10] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [11] 0 0
Part 1: Cmax following administration of GSK3368715 in Fasted state - Cmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [11] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [12] 0 0
Part 1: Tmax following administration of GSK3368715 in Fed state - Tmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [12] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [13] 0 0
Part 1: Tmax following administration of GSK3368715 in Fasted state - Tmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [13] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [14] 0 0
Part 1: AUC (0-t) following administration of GSK3368715 in Fed state - AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [14] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [15] 0 0
Part 1: AUC (0-t) following administration of GSK3368715 in Fasted state - AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [15] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [16] 0 0
Part 1: AUC (0-infinify) following administration of GSK3368715 in Fed state - AUC(0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [16] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [17] 0 0
Part 1: AUC (0-infinity) following administration of GSK3368715 in Fasted state - AUC(0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [17] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [18] 0 0
Part 1: AUC (0-tau) following administration of GSK3368715 in Fed state - AUC(0-tau) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [18] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [19] 0 0
Part 1: AUC (0-tau) following administration of GSK3368715 in Fasted state - AUC(0-tau) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [19] 0 0
Pre-dose,15,30 minutes(min),1,1.5,2,3,4,6,8,12,24,48,72hours(h) post-dose on Day 1,4,5; Pre-dose,30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle2 (Each cycle will be of 21days)
Secondary outcome [20] 0 0
Part 2: Number of participants with AEs and SAEs - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Timepoint [20] 0 0
Up to 3.9 years
Secondary outcome [21] 0 0
Part 2: Number of participants with AEs by maximum grade - An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AEs will be graded using CTCAE V5.0.
Timepoint [21] 0 0
Up to 3.9 years
Secondary outcome [22] 0 0
Part 2: Progression-free survival (PFS) - PFS is defined as the time from the first dose of study intervention to disease progression or death due to any cause, whichever occurs earlier.
Timepoint [22] 0 0
Up to 3.9 years
Secondary outcome [23] 0 0
Part 2: Cmax following administration of GSK3368715 - Cmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [23] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose (Day1) of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [24] 0 0
Part 2: Tmax following administration of GSK3368715 - Tmax of GSK3368715 is to be derived from the PK samples collected.
Timepoint [24] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose (Day1) of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [25] 0 0
Part 2: AUC (0-t) following administration of GSK3368715 - AUC(0-t) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [25] 0 0
Pre-dose,15,30 min,1, 1.5, 2,3,4,6,8,12,24,48,72 h post-dose (Day1) of each cycle; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [26] 0 0
Part 2: AUC (0-infinity) following single dose administration of GSK3368715 - AUC (0-infinity) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [26] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1 of each cycle (Each cycle will be of 21 days)
Secondary outcome [27] 0 0
Part 2: AUC (0-tau) following repeat dose administration of GSK3368715 - AUC (0-tau) of GSK3368715 is to be derived from the PK samples collected.
Timepoint [27] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [28] 0 0
Part 2: Ctau following repeat dose administration of GSK3368715 - Ctau of GSK3368715 is to be derived from the PK samples collected.
Timepoint [28] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min,1,2, 3,4,6,8,12,24 h post-dose on Day 15 of each cycle; Pre-dose on Days 22 and at every 4 weeks from Cycle 2 (Each cycle will be of 21 days)
Secondary outcome [29] 0 0
Part 2: Time invariance ratio following administration of GSK3368715 - Time invariance ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Timepoint [29] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)
Secondary outcome [30] 0 0
Part 2: Accumulation ratio following administration of GSK3368715 - Accumulation ratio of GSK3368715 is to be derived from the PK samples collected wherever data permits.
Timepoint [30] 0 0
Pre-dose, 15, 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose on Day 1; Pre-dose, 30 min, 1, 2, 3, 4, 6, 8, 12, 24 h post-dose on Day 15 of each cycle (Each cycle will be of 21 days)

Eligibility
Key inclusion criteria
- 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of malignancy other than the disease under study. Participants who have been
disease-free for 5 years, or participants with a history of completely resected
non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Participants with second malignancies that are indolent or definitively treated may be
enrolled even if less than 5 years have elapsed since treatment.

- Primary central nervous system (CNS) tumors, Glioblastoma multiforme (GBM),
symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Participants previously treated for these conditions that have had stable
CNS disease (verified with consecutive imaging studies) for >1 months, are
asymptomatic and off corticosteroids, or are on stable dose of corticosteroids for at
least 1 month prior to study Day 1 are permitted. Stability of brain metastases must
be confirmed with imaging. Participants treated with gamma knife therapy can be
enrolled 2 weeks post-procedure as long as there are no post-procedure
complications/they are stable.

- Any severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding
episodes, or active infection).

- Any serious and/or unstable pre-existing medical, psychiatric disorder, or other
conditions that could interfere with participant's safety, obtaining informed consent
or compliance to the study procedures, in the opinion of the Investigator.

- Any clinically significant gastrointestinal (GI) abnormalities that may alter
absorption such as malabsorption syndrome or major resection of the stomach and/or
bowels.

- History of known human immunodeficiency virus (HIV) infection or positive HIV test
result at screening.

- Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
result at screening to first dose of study intervention.

- Any of the following cardiac abnormalities: Uncontrolled high blood pressure; any
history of coronary artery disease, including acute coronary syndromes, myocardial
infarction, unstable angina, and history of coronary angioplasty, or stenting;
presence of a cardiac pacemaker or implanted defibrillator; atrioventricular
(AV)-block (asymptomatic 2nd degree Type II or 3rd degree and any degree AV block if
related to heart disease or if symptomatic), right bundle branch block (RBBB), left
bundle branch block (LBBB), and any fasicular hemiblocks; A QRS interval at Screening
or Baseline >110 msec; participants with any symptomatic or sustained arrhythmias
(past or present), including but not limited to: Atrial fibrillation, Atrial flutter,
Ventricular tachycardia, Ventricular fibrillation, Supraventricular tachycardia;
Current or past congestive heart failure; Evidence of a left ventricular ejection
fraction below the institutional lower limit of normal on Screening echocardiogram;
Evidence of significant structural heart disease on echocardiography at Screening
(including any valvular disease greater than "mild" in severity); Cardiac troponin >
upper limit of the reference range at Screening.

- Treatment with any local or systemic anti-neoplastic therapy or investigational
anticancer agent within 14 days or 4 half-lives, whichever is longer, up to a maximum
wash-out period of 28 days prior to initiation of study drug administration.
Anti-androgen therapies for prostate cancer, such as bicalutamide, must be stopped 28
days prior to first dose of GSK3368715. Second-line hormone therapies such as
enzalutamide or abiraterone should be stopped 14 days prior to enrolment. Participants
with prostate cancer may remain on luteinizing hormone-releasing hormone (LHRH)
agonists or antagonists and/or low-dose prednisone or prednisolone (up to 10
milligrams per day [mg/day]). Nitrosureas and mitomycin C must be stopped within 42
days prior to first dose of GSK3368715.

- Allogeneic hematopoietic stem-cell transplantation.

- Toxicities from previous anti-cancer therapies have not resolved to Baseline or
National Cancer Institute (NCI) CTCAE V5.0. <=Grade 1 (except fatigue and alopecia
[permissible at any grade] and peripheral neuropathy [which must be <= Grade 2]) at
the time of starting study intervention.

- Major surgery (i.e. requiring general anesthesia) within 3 weeks before screening, or
not fully recovered from major surgery, or major surgery planned during study
participation. Planned surgical procedures to be conducted under local anesthesia are
allowed.

- Prior organ transplantation.

- Concurrent anti-coagulation therapy. Treatment with low-molecular heparin is allowed.

- Current use of a prohibited medication or planned use of any forbidden medications
during intervention with GSK3368715.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or Medical
Monitor, contraindicates their participation.

- Participant is considered high-risk for VTE as defined by either Khorana Score of
greater than or equal to 3 or prior medical history of VTE.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Spain
State/province [8] 0 0
Barcelona
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Arginine methylation mediated by protein arginine methyl-transferases (PRMTs) is an important
post-translational modification of proteins involved in a diverse range of cellular
processes. Misregulation and overexpression of PRMT1 (a type I PRMT) has been associated with
a number of solid and hematopoietic cancers. GSK3368715 leads to inhibition of tumor cell
growth across tumor types with cytotoxic response observed in lymphoma, acute myeloid
leukemia (AML) and a subset of solid tumor cell lines. This study will assess the safety,
pharmacokinetics (PK), pharmacodynamics (PD), food effect and preliminary clinical activity
of GSK33368715 in participants with relapsed/refractory DLBCL and selected solid tumors with
frequent methyl-thioadenosine phosphorylase (MTAP)-deficiency. The study will consist of two
parts. In Part 1 (Dose Escalation) escalating doses of GSK3368715 will be evaluated and
recommended phase 2 dose (RP2D) will be established in participants with selected solid
relapsed/refractory tumors. Once a RP2D is identified, a food effect sub-study will be
initiated to determine the effect of a high-fat, high calorie meal on the bioavailability of
GSK3368715. In Part 2 (Dose Expansion), this RP2D will be further investigated in two
expansion cohorts; participants with DLBCL (Expansion Cohort 2A) and relapsed/refractory
solid tumors including pancreatic, bladder, and non-small cell lung cancer (NSCLC)(Expansion
Cohort 2B). The study includes a screening period, an intervention period and follow up.
Trial website
https://clinicaltrials.gov/show/NCT03666988
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03666988