Last updated: 03/11/2021 09:10:09

First-time-in-human (FTIH) study of GSK3145095 alone and in combination with other anticancer agents in adults with advanced solid tumors

GSK study ID
205013
See study documents
Clinicaltrials.gov ID
NCT03681951
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I/II, Open-Label Study to Investigate the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of GSK3145095 Administered Alone and in Combination with Anticancer Agents Including Pembrolizumab in Adult Participants with Selected Advanced Solid Tumors
Trial description: In an unbiased CRISPR screen, RIPK1 was identified as a top gene contributing to immunotherapy resistance. In addition, RIPK1 has been reported to drive pancreatic oncogenesis. In murine models, inhibition of RIPK1 kinase activity in the pancreatic tumor microenvironment leads to the replacement of tumor-permissive myeloid infiltrates with innate cells that promote an effective antitumor response by adaptive cells. The investigators hypothesize that inhibition of RIPK1 in human pancreatic cancer subjects will modulate the immune infiltrate to sensitize tumors to checkpoint blockade.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Number of subjects with adverse events (AEs) and serious adverse events (SAEs)-Part 1

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs-Part 2

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs defined by severity-Part 1

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs defined by severity-Part 2

Timeframe: Up to 2 years

Number of subjects with dose-limiting toxicities (DLTs)-Part 1

Timeframe: Up to 2 years

Number of subjects with DLTs-Part 2

Timeframe: Up to 2 years

Percentage of subjects achieving complete response or partial response based on response evaluation criteria in solid tumors (RECIST) 1.1 criteria Part 3

Timeframe: Up to 2 years

Percentage of subjects achieving complete response or partial response based on RECIST 1.1 criteria Part 4

Timeframe: Up to 2 years

Secondary outcomes:

Overall response rate (ORR) based on RECIST 1.1 criteria-Part 1

Timeframe: Up to 2 years

ORR based on RECIST 1.1 criteria-Part 2

Timeframe: Up to 2 years

Number of subjects with progression-free survival (PFS)-Part 3

Timeframe: Up to 2 years

Number of subjects with PFS-Part 4

Timeframe: Up to 2 years

Number of subjects with overall survival -Part 3

Timeframe: Up to 2 years

Number of subjects with overall survival -Part 4

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs-Part 3

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs-Part 4

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs defined by severity-Part 3

Timeframe: Up to 2 years

Number of subjects with AEs and SAEs defined by severity-Part 4

Timeframe: Up to 2 years

Area under the plasma drug concentration versus time curve (AUC [0-t]) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

(AUC 0-t) following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Area under the concentration-time curve over the dosing interval (AUC [0-tau]) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

AUC (0-tau) following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Maximum observed plasma drug concentration (Cmax) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Cmax following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Minimum observed plasma drug concentration (Cmin) following single dose of GSK3145095-Part 1

Timeframe: Day 1:24 hours post-dose

Cmin following single dose of GSK3145095-Part 2

Timeframe: Day 1:24 hours post-dose

Time to maximum observed plasma drug concentration (tmax) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

tmax following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Clearance (CL/F) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

CL/F following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Volume of distribution (V/F) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

V/F following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Terminal half-life (t1/2) following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

t1/2 following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

AUC (0-t) following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

AUC (0-t) following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

AUC (0-tau) following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

AUC (0-tau) following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Cmax following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Cmax following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Cmin following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Cmin following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

tmax following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

tmax following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

CL/F following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

CL/F following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

V/F following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

V/F following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

t1/2 following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

t1/2 following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using AUC following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using Cmax following single dose of GSK3145095-Part 1

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using AUC following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using Cmax following repeat dose of GSK3145095-Part 1

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using AUC (0-tau) following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using Cmax following single dose of GSK3145095-Part 2

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using AUC (0-tau) following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using Cmax following repeat dose of GSK3145095-Part 2

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Accumulation ratio following repeat dose of GSK3145095-Part 1

Timeframe: Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Accumulation ratio following repeat dose of GSK3145095-Part 2

Timeframe: Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Time invariance following repeat dose of GSK3145095-Part 1

Timeframe: Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Time invariance following repeat dose of GSK3145095 of GSK3145095-Part 2

Timeframe: Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Plasma concentration of pembrolizumab -Part 2

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

Cmax of pembrolizumab-Part 2

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

AUC (0-tau) of pembrolizumab-Part 2

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22 (pre-dose)

Cmin of pembrolizumab-Part 2

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

AUC (0-t) following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Cmax following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

tmax following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

t1/2 following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

AUC (0-t) following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Cmax following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

tmax following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

t1/2 following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

AUC (0-t) following single dose of pembrolizumab-Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

AUC (0-tau) following single dose of pembrolizumab -Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

Cmax following single dose of pembrolizumab -Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

tmax following single dose of pembrolizumab -Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

t1/2 following single dose of pembrolizumab -Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

AUC (0-t) following repeat dose of pembrolizumab -Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

AUC (0-tau) following repeat dose of pembrolizumab -Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

Cmax following repeat dose of pembrolizumab -Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

tmax following repeat dose of pembrolizumab -Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

t1/2 following repeat dose of pembrolizumab -Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

Dose proportionality using AUC following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using Cmax following single dose of GSK3145095-Part 3

Timeframe: Day 1:Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 hours

Dose proportionality using AUC (0-tau) following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using Cmax following repeat dose of GSK3145095-Part 3

Timeframe: Days 15,16: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Accumulation ratio following repeat dose of GSK3145095-Part 3

Timeframe: Days 1: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre-dose,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose; Day 15: 0.5,1,2,3,6,8 hour post evening dose

Time invariance following repeat dose of GSK3145095-Part 3

Timeframe: Days 1: Pre - dose ,0.5,1,1.5,2,3,4,6,8,10,24 hour; Days 15: Pre - dose ,0.5,1,1.5,2,3,4,6,8,10,24 hour post morning dose ; Day 15:0.5,1,2,3,6,8 hour post evening dose

Dose proportionality using AUC following single dose of pembrolizumab-Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

Dose proportionality using Cmax following single dose of pembrolizumab-Part 3

Timeframe: Study Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hour after end of infusion

Dose proportionality using AUC (0-tau) following repeat dose of pembrolizumab-Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years.

Dose proportionality using Cmax following repeat dose of pembrolizumab-Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years.

Accumulation ratio following repeat dose of pembrolizumab-Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

Time invariance following repeat dose of pembrolizumab-Part 3

Timeframe: Day 1: pre-dose, 0.5 hour (within 30 minutes after end of infusion), 24 hours after end of infusion; Days 8,15 (anytime during visit); Days 22,43,64 and every 21 days thereafter (pre-dose), for up to 2 years

Interventions:
  • Drug: GSK3145095
  • Drug: Pembrolizumab
    • Enrollment:
    8
    Primary completion date:
    2019-13-08
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Neoplasms, Pancreatic
    Product
    GSK3145095, GSK3371846
    Collaborators
    Parexel
    Study date(s)
    November 2018 to August 2019
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Subjects must provide signed, written informed consent.
    • Male and female subjects, age >=18 years (at the time consent is obtained). a) Male subjects are eligible to participate if they agree to the following during the study treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment: Refrain from donating sperm, 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: male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year. b) female subjects are eligible to participate if they are not either pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP), is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent per year), with low user dependency during the study treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of the contraceptive method. Therefore, a barrier method is also required for subjects using a hormonal option (including hormonal intrauterine device [IUD], oral contraceptive pills/ patch/ vaginal inserts, and hormonal implants) and both highly effective methods of contraception should be utilized during the treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment.If a highly effective non-hormonal method is used, then only one method of contraception is required (by a female participant or partner of a male participant; in either situation the male partner must still use a male condom in addition) during the treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations) within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive. If the subject hasn’t been on an acceptable method of contraception for at least 2 weeks prior to start of therapy, pregnancy testing must be done weekly for the first month of treatment. Additional requirements for pregnancy testing during and after study treatment. 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.
    • Prior treatment with the following agents: Agents affecting tumor associated macrophage function or number, including but not limited to inhibitors of Receptor-interacting protein 1 (RIP1), Receptor-interacting protein 3 (RIP3), Colony stimulating factor 1 receptor (CSFR-1), C-C chemokine receptor type 2 (CCR2), and Cluster of differentiation 40 (CD40). Other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy, within 14 days or 5 half-lives (from last dose of prior treatment to first dose of GSK3145095), whichever is shorter. Prior radiation therapy is permissible if at least one non-irradiated measurable lesion is available for assessment via RECIST version 1.1. No washout after palliative radiation is required. Investigational therapy within 14 days or 5 half-lives (from last dose of prior treatment to first dose of GSK3145095), whichever is shorter.
    • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Subjects must provide signed, written informed consent.
    • Male and female subjects, age >=18 years (at the time consent is obtained). a) Male subjects are eligible to participate if they agree to the following during the study treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment: Refrain from donating sperm, 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: male condom and female partner to use an additional highly effective contraceptive method with a failure rate of <1 percent per year. b) female subjects are eligible to participate if they are not either pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP), is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1 percent per year), with low user dependency during the study treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. Hormonal contraception may be susceptible to interaction with the study drug, which may reduce the efficacy of the contraceptive method. Therefore, a barrier method is also required for subjects using a hormonal option (including hormonal intrauterine device [IUD], oral contraceptive pills/ patch/ vaginal inserts, and hormonal implants) and both highly effective methods of contraception should be utilized during the treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment.If a highly effective non-hormonal method is used, then only one method of contraception is required (by a female participant or partner of a male participant; in either situation the male partner must still use a male condom in addition) during the treatment period and for at least 15 days (Part 1) and 120 days (Parts 2-4) after the last dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations) within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the subject must be excluded from participation if the serum pregnancy result is positive. If the subject hasn’t been on an acceptable method of contraception for at least 2 weeks prior to start of therapy, pregnancy testing must be done weekly for the first month of treatment. Additional requirements for pregnancy testing during and after study treatment. 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.
    • Histological documentation of locally advanced, recurrent or PDAC (Part 1), non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), or melanoma (Part 2) that has progressed after standard therapy appropriate for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate. Subjects should have received at least one, but not more than 2 prior lines of therapy for advanced disease including both standards of care and investigational therapies. Subjects whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority-approved appropriate targeted therapy for their tumor types before enrollment.
    • All subjects in Parts 1 and 2 must consent to provide a fresh biopsy during screening of a primary tumor lesion or from other metastases (e.g. liver, lung, etc.), and a second biopsy after approximately 5 weeks of treatment.
    • Measurable disease per RECIST version 1.1. Palpable lesions that are not measurable by radiologic or photographic evaluations may not be utilized as the only measurable lesion. Subjects are encouraged to provide a pre-Baseline scan (within 24 weeks before the Baseline scan) to support exploratory investigation of tumor growth kinetics.
    • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1.
    • Life expectancy of at least 12 weeks.
    • Adequate organ function.
    • QT duration corrected for heart rate by Fridericia’s formula (QTcF) <450 milliseconds (or QTcF <480 milliseconds for subjects with bundle branch block).
    Exclusion criteria:
    • Prior treatment with the following agents: Agents affecting tumor associated macrophage function or number, including but not limited to inhibitors of Receptor-interacting protein 1 (RIP1), Receptor-interacting protein 3 (RIP3), Colony stimulating factor 1 receptor (CSFR-1), C-C chemokine receptor type 2 (CCR2), and Cluster of differentiation 40 (CD40). Other anticancer therapy, including chemotherapy, targeted therapy, and biological therapy, within 14 days or 5 half-lives (from last dose of prior treatment to first dose of GSK3145095), whichever is shorter. Prior radiation therapy is permissible if at least one non-irradiated measurable lesion is available for assessment via RECIST version 1.1. No washout after palliative radiation is required. Investigational therapy within 14 days or 5 half-lives (from last dose of prior treatment to first dose of GSK3145095), whichever is shorter.
    • Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
    • Toxicity from previous treatment: Subjects whose toxicity related to prior treatment has not resolved to <=Grade 1 (except alopecia, hearing loss, Grade <=2 neuropathy or endocrinopathy managed with replacement therapy) are not eligible.
    • Malignancy other than disease under study, except as noted: Subject with any other malignancy from which the subject has been disease-free for more than 2 years and, in the opinion of the principal investigators and GlaxoSmithKline (GSK) Medical Monitor, will not affect the evaluation of the effects of this clinical trial treatment on currently targeted malignancy, can be included in this clinical trial.
    • Major surgery <=4 weeks before the first dose of study treatment. Subjects must have also fully recovered from any surgery (major or minor) and/or its complications before initiating study treatment.
    • Active autoimmune disease that has required systemic treatment within the last 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    • Concurrent medical condition requiring the use of systemic immunosuppressive medications within 28 days before the first dose of study treatment. Physiologic doses of corticosteroids for treatment of endocrinopathies or steroids with minimal systemic absorption, including topical, inhaled, or intranasal corticosteroids, may be continued if the subject is on a stable dose.
    • Active infection (including active herpes zoster infection), known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C.
    • Current active liver or biliary disease (except for Gilbert’s syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
    • Known current drug or alcohol abuse.
    • Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
    • Receipt of any live vaccine within 4 weeks before starting study treatment.
    • Recent history of allergen desensitization therapy within 4 weeks before starting study treatment (applies to subjects enrolled in Parts 2 and 3 only).
    • History or evidence of cardiovascular risk including any of the following: recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant electrocardiogram (ECG) abnormalities including second degree (Type II) or third degree atrioventricular block. Documented cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before beginning screening. Documented congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system. Recent (within the past 6 months) history of symptomatic pericarditis.
    • Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia.
    • History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
    • Recent history (within 14 days) of ascites or pleural effusions requiring drainage.
    • Any serious and/or unstable pre-existing medical, psychiatric disorder, or other condition that could interfere with the subjects safety, obtaining informed consent, or compliance to the study procedures.
    • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective Institutional Review Board (IRB) approval (by chair or designee) is given allowing exception to this criterion for a specific subject.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Houston, Texas, United States, 77030
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Indianapolis, Indiana, United States, 46202
    Status
    Study Complete
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    Location
    GSK Investigational Site
    New York, New York, United States, 10016
    Status
    Study Complete
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    Location
    GSK Investigational Site
    New York, New York, United States, 10032
    Status
    Study Complete
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    Location
    GSK Investigational Site
    New York, New York, United States, 10065
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Philadelphia, Pennsylvania, United States, 19111
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
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    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2019-13-08
    Actual study completion date
    2019-13-08

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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