This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
167
60 mg/mL concentration; administered intravenously (IV)
25 mg/mL concentration; administered IV
Oxaliplatin \[5 mg/mL concentration; administered IV\], leucovorin \[10 mg/mL concentration; administered IV\] (or levoleucovorin \[10 mg/mL concentration; administered IV\]), and 5-fluorouracil \[50 mg/mL concentration; administered IV\]
Irinotecan \[20 mg/mL concentration; administered IV\], leucovorin \[10 mg/mL concentration; administered IV\] (or levoleucovorin \[10 mg/mL concentration; administered IV\]), and 5-fluorouracil \[50 mg/mL concentration; administered IV\]
10 mg/mL concentration; administered IV
6 mg/mL concentration; administered IV
60 mg tablet; administered orally
University of California LA
Los Angeles, California, United States
WA Uni School Of Med
St Louis, Missouri, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Novartis Investigative Site
Melbourne, Victoria, Australia
Novartis Investigative Site
Brussels, Belgium
Part 1a/b (Cohorts A and B): Change in high-sensitivity C-reactive protein (hs-CRP) after first dose of gevokizumab monotherapy
Log scale change of hs-CRP at Day 15 from baseline
Time frame: Baseline, Day 15
Part 1b (Safety run-in): Number of dose limiting toxicities (DLTs) [Cohort C and Cohort D]
DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Time frame: First 4 weeks of combination treatment
Part 1b (Safety run-in): Number of DLTs [Cohort A and Cohort B]
DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the beginning of treatment with gevokizumab in combination with the SOC anti-cancer therapies and meets any of the protocol specified criteria.
Time frame: First 6 weeks of combination treatment
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort A subjects at RDE level]
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Time frame: At 15 months
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort B subjects at RDE level]
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Time frame: At 9 months
Part 2 (Expansion) and Part 1b (Safety run-in): Progression free survival (PFS) rate [Cohort C subjects at RDE level]
PFS rate is defined as the percentage of participants who have not progressed or died due to any cause within a specified timeframe after study treatment initiation. Progression will be assessed per investigator assessment using RECIST v1.1.
Time frame: At 6 months
Overall response rate (ORR) per investigator assessment using RECIST v1.1
ORR is defined as the proportion of subjects with best overall response (BOR) of complete response (CR) or partial response (PR), according to RECIST 1.1
Time frame: Up to 5 years
Duration of response (DOR) per investigator assessment using RECIST v1.1
Duration of response is defined as the time from first documented response of CR or PR to date of first documented progression or death due to any cause, according to RECIST 1.1 criteria
Time frame: Up to 5 years
Disease Control Rate (DCR) per investigator assessment using RECIST v1.1
DCR is defined as the proportion of subjects with a BOR of CR, PR, or stable disease (SD), according to RECIST 1.1.
Time frame: Up to 5 years
Overall survival (OS)
OS is defined as the time from date of first dose of study treatment to date of death due to any cause.
Time frame: Up to 5 years
PFS by baseline hs-CRP category using RECIST 1.1 [Cohort A and B at RDE level]
PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
Time frame: Up to 5 years
PFS for subjects from Part 1b at doses other than RDE level (Cohort A and Cohort B)
PFS is defined as the time from the date of first dosing of study drug to the date of the first documented progression or death due to any cause.
Time frame: Up to 5 years
Number of patients with anti-drug antibodies for gevokizumab in the combination regimens
Incidence of immunogenicity for gevokizumab
Time frame: Up to 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Novartis Investigative Site
Edegem, Belgium
Novartis Investigative Site
Leuven, Belgium
Novartis Investigative Site
Calgary, Alberta, Canada
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Santiago, Chile
...and 24 more locations