Advanced Microsatellite Stable Colorectal Cancer
Conditions
Brief summary
The goal of this clinical study is to learn more about the study drug, Denikitug (DEN, GS-1811), to evaluate the efficacy and safety of Denikitug Monotherapy and Denikitug-based Combinations in participants with advanced microsatellite stable (MSS) colorectal cancer (CRC). The primary objective of this study is to assess the effect of DEN as monotherapy and in combination with nivolumab (NIVO) or trifluridine-tipiracil (FTD-TPI) and bevacizumab (BVZ) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1).
Interventions
DRUGDenikitug
Administered Intravenously
DRUGNivolumab
Administered Intravenously
DRUGBevacizumab
Administered Intravenously
Administered orally
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Medical History/Physical Characteristics * Histologically or cytologically confirmed unresectable, recurrent, or locally advanced or metastatic microsatellite stable colorectal cancer (MSS CRC) (adenocarcinoma, excluding appendix cancer). * Documented MSS or proficient mismatch repair (pMMR) disease by local assessment using a validated polymerase chain reaction (PCR) (microsatellite status) and/or immunohistochemistry (IHC) mismatch repair (MMR) assay is required. * Has received up to 2 prior lines of systemic therapy for advanced or metastatic CRC, which must have included at least fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies if indicated; and if applicable: anti-vascular endothelial growth factor (VEGF) therapy, anti epidermal growth factor receptor (EGFR) therapy, encorafenib or adagrasib/sotorasib. * Documented progressive disease (PD) by computed tomography (CT) or magnetic resonance imaging (MRI) during or after the most recent therapy per RECIST Version 1.1 criteria by investigator assessment. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. Laboratory Assessments * Have adequate organ function. Key
Exclusion criteria
with: Medical Conditions/History: * Significant cardiovascular disease. * History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years. * History of (noninfectious) pneumonitis/interstitial lung disease or current pneumonitis/ interstitial lung disease. * History of gastrointestinal (GI) perforation, permanent ileostomy, abdominal abscess or fistula within 6 months, active or uncontrolled GI bleeding within 4 weeks, or any condition associated with significant risk of bleeding or perforation (eg, untreated varices, tumor erosion, recent GI surgery). Prior/Concurrent Therapy or Clinical Study Experience Prior treatment with: * Trifluridine-tipiracil, regorafenib, or fruquitinib. * Any immuno-oncology therapy. * Anticancer biologic agent within 4 weeks prior to randomization or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to randomization and have not recovered (ie, Grade 2 or less) from AEs from prior anticancer therapy at the time of randomization. Individuals in observational studies are eligible. * Allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to 60 months | ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST Version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) | Up to 60 months | DOR is defined as the time from first response (CR or PR) as assessed by investigator, per RECIST Version 1.1 until the date of first documented progressive disease (PD) or death, whichever comes first. |
| Progression-Free Survival (PFS) | Up to 60 months | PFS is defined as the time from date of randomization until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1. |
| Overall Survival (OS) | Up to 60 months | OS is defined as the length of time from randomization until the date of death from any cause. |
| Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | First dose date up to 120 days post last dose, up to 60 months | — |
| Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 | First dose date up to 120 days post last dose, up to 60 months | — |
| Pharmacokinetic (PK) Parameter: Serum concentration of Denikitug | Up to 36 months | — |
| PK Parameter: Cmax for Denikitug | Up to 36 months | Cmax is defined as the maximum observed concentration. |
| PK Parameter: AUCall for Denikitug | Up to 36 months | AUCall is defined as the cumulative areas under the curve for all time points. |
| Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug | Up to 36 months | — |
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed