This is a Phase I/II, open-label, first-in human study of GRWD5769 alone, and in combination with another anti-cancer agent in advanced solid cancers.
GRWD5769 is as a potential new treatment for advanced or metastatic solid malignancies. GRWD5769 works by stopping an enzyme in the body, called endoplasmic reticulum aminopeptidase 1 (ERAP1), from working. ERAP1 is part of how the body recognizes the presence of a cancer tumour and helps trigger the immune system to fight the cancer. However, in patients with cancer, the immune system cells can become exhausted and no longer work effectively. By blocking ERAP1 it makes the tumour look different to the immune system and so the immune system starts fighting the cancer again. GRWD5769 has the potential of producing clinically meaningful improvements in monotherapy and in combination with therapy like cemiplimab (Libtayo®) by enhancing the antitumour immune response. Who can participate? Patients with advanced or metastatic solid malignancy aged 18 years or older. What does the study involve? This study consists of Module 1 (Parts A to D), which will look at the effects of GRWD5769 when given alone and Module 2 (Parts A to D) which will look at the effects of GRWD5769 when given in combination with another anticancer drug called Libtayo® (cemiplimab).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
Module 1 will initially be conducted in 4 study parts: Part A: Monotherapy dose escalation (where the safety of increasing doses of GRWD5769 will initially be assessed in a small group of patients, overseen by a safety review committee) Part B: (Optional) Monotherapy dose expansion part (to look at the effect of GRWD5769 on the body, and of the body on GRWD5769, at particular dose levels to include evaluation of biopsies of tumour tissue) Part C: (Optional) Intra-patient dose escalation (where a patient may receive three different GRWD5769 doses so that blood levels at each dose can be measured in an individual) Part D: Monotherapy dose expansion group(s) (where a dose of GRWD5769 may be chosen to be evaluated in specific types of cancer)
Module 2 will initially be conducted as 3 study parts, similar to those above, but looking at GRWD5769 when given in combination with cemiplimab: Part A: Combination therapy dose escalation (like Module 1 Part A) Part B: (Optional) Combination therapy dose expansion part (like Module 1 Part B) Part C: Combination therapy dose expansion group(s) (where a dose of GRWD5769 given with cemiplimab will be evaluated in specific types of cancer) Part D: Randomised dose optimisation, combination therapy (where 3 doses of GRWD5769 given with cemiplimab will be evaluated in specific types of cancer)
Number of treatment emergent and treatment related AEs
Incidence of treatment emergent and treatment related AEs assessed from start of study drug to 30 days post last dose of GRWD5769 (Module 1) or to 90 days post last dose of cemiplimab (Module 2 Parts A-C).
Time frame: From first dose to 30 days after last dose of GRWD5769 for Module 1 and 90 days after last dose of cemiplimab for Module 2 Parts A-C.
Incidence of Dose limiting toxicities (DLT)
Incidence of Dose limiting toxicities (DLT) during the DLT period which commences Cycle 0 Day 1 and continues to 21 days after Cycle 1 Day 1
Time frame: End of cycle 1 (each cycle is 21 days)
Comparative efficacy (for Module 2D only)
Comparative efficacy will be evaluated or assessed using the change in dimension over time of RECIST Target Lesions from baseline and on-study scans recorded at weeks 8 and 16
Time frame: From baseline to week 16
GRWD5769 Plasma PK Trough concentration
Time frame: Up to approximately 1 year
Objective response rate (ORR)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (ORR) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Disease specific tumour markers
Changes in any applicable disease-specific tumour markers assessed pre-treatment, Day 1 of each cycle from Cycle 2 onwards, at each 6-weekly safety extension visit, at the end of study visit and at follow up visit 30 days post last dose of GRWD5769.
Time frame: Up to approximately 1 year
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GenesisCare Research
Adelaide, Australia
WITHDRAWNSouthern Oncology Clinical Research Unit (SOCRU)
Bedford Park, Australia
RECRUITINGBlacktown Hospital
Blacktown, Australia
RECRUITINGKinghorn Cancer Centre (KCC)
Darlinghurst, Australia
RECRUITINGAustin Health
Heidelberg, Australia
RECRUITINGAlfred Health
Melbourne, Australia
RECRUITINGMater Research
South Brisbane, Australia
RECRUITINGCancer Care Wollongong
Wollongong, Australia
RECRUITINGCentre Léon Bérard
Lyon, France
RECRUITINGInstitut Paoli-Calmettes
Marseille, France
RECRUITING...and 19 more locations
GRWD5769 Plasma PK Cmax
Cmax = Maximum observed concentration
Time frame: Up to approximately 1 year
GRWD5769 Plasma PK Tmax
Tmax = Time to maximum observed concentration
Time frame: Up to approximately 1 year
GRWD5769 Plasma PK AUC0-t
AUC0-t = Area under the concentration-time curve
Time frame: Up to approximately 1 year
GRWD5769 Plasma PK Half-life
Time frame: Up to approximately 1 year
GRWD5769 Plasma PK Oral Clearance
Time frame: Up to approximately 1 year
GRWD5769 Plasma PK Vss/F
Vss/F = Absorption-dependent apparent volume of distribution in steady state
Time frame: Up to approximately 1 year
Disease Control Rate (DCR)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (DCR) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Stable Disease Rate (SDR)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (SDR) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Time To Response (TTR)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (TTR) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Duration Of Response (DOR)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (DOR) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Progression - Free Survival (PFS)
Preliminary efficacy of GRWD5769 will be assessed by: Tumour response (PFS) by RECIST 1.1 or iRECIST as determined by CT/MRI scans performed every 8 weeks until participant disease progression or withdrawal.
Time frame: Up to approximately 1 year
Number of treatment emergent and treatment related AEs (for Module 2D only)
Incidence of treatment emergent and treatment related AEs assessed from start of study drug to 90 days post last dose of cemiplimab (for Module 2D only).
Time frame: 90 days after last dose of cemiplimab
Incidence of Dose limiting toxicities (DLT) (for Module 2D only)
Incidence of Dose limiting toxicities (DLT) during the DLT period which commences Cycle 0 Day 1 and continues to 21 days after Cycle 1 Day 1
Time frame: End of cycle 1 (each cycle is 21 days)
Overall Survival
Preliminary efficacy of GRWD5769 will be assessed by: Overall survival assessed from start of study drug until participant withdrawal or death (for Module 2C and 2D only).
Time frame: Up to approximately 1 year