Study of Denikitug (GS-1811) Given Alone or With Nivolumab or With Chemotherapy in Adults with Advanced Colorectal Cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Gilead Sciences Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Pharmacogenomic, Efficacy, Therapy, Others

To assess the effect of denikitug (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).

Secondary objectives 4

1. To assess the effect of DEN as monotherapy and in combination with XXXX or FTD-TPI and BVZ on duration of response (DOR) and progression-free survival (PFS) as assessed by the investigator according to RECIST Version 1.1.
2. To assess the effect of DEN as a monotherapy and in combination with XXXX or FTD-TPI and BVZ on overall survival (OS).
3. To evaluate the safety and tolerability of DEN as monotherapy and in combination with NIVO or FTD-TPI and BVZ.
4. To evaluate pharmacokinetics (PK) and immunogenicity (antidrug antibody [ADA]) of DEN as monotherapy and in combination with XXXXX

Conditions and MedDRA coding

Advanced Microsatellite Stable (MSS) Colorectal Cancer (CRC)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Medical History/Physical Characteristics MH1. Histologically or cytologically confirmed unresectable, recurrent, or locally advanced or metastatic 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.
2. MH2. Has received up to 2 prior lines of systemic therapy for advanced or metastatic CRC, which must have included at least the following therapies if indicated and approved/available in the country where the participant is enrolled/randomized. Fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapies; if applicable in combination with: - An anti-VEGF agent (if eligible) or - An anti-EGFR agent (for participants with left sided, B-Raf proto-oncogene (BRAF)/rat sarcoma [RAS] wild-type tumors). Encorafenib in combination with an anti-EGFR agent or encorafenib in combination with an anti-EGFR agent and modified 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) (if BRAF V600E mutated). Adagrasib or sotorasib in combination with an anti-EGFR agent (if Kirsten rat sarcoma [KRAS] G12C mutated). Note: Perioperative, neoadjuvant, or adjuvant chemotherapy regimens will not count as a prior regimen unless PD has occurred during or within 6 months of completing neoadjuvant/adjuvant therapy. Note: Patients with known human epidermal growth receptor 2 (HER2)-positive tumors are not eligible.
3. MH3. 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.
4. MH5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
5. LA2. Have adequate organ function as indicated by the following screening laboratory values: Organ/ Tissue Function: Adequate Hematologic function - Status: Without requiring a transfusion or growth factor within 2 weeks before screening laboratory assessments - Parameters*: ANC: ≥ 1.5 x 109/L ; Platelets: ≥ 100 x 109/L; Hemoglobin: ≥ 9g/dL Adequate hepatic function - Parameters*: Total bilirubin: ≤ 1.5 x ULN or ≤ 3 x ULN in participants with liver metastases or Gilbert’s syndrome or a genetic equivalent; AST and ALT: ≤ 2.5 x ULN or ≤ 5 x ULN if known liver metastases Adequate renal function - Parameters*: Creatinine clearance: ≥ 50 mL/min by the Cockcroft Gault method; The participant`s urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then a 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation the study Adequate coagulation - Status: For participants receiving anticoagulant therapy (except platelet anti aggregates) the adequate therapeutic levels of INR should be confirmed - Parameters*:y. INR or PT: ≤ 1.5 x ULN, unless the participant is receiving anticoagulant therapy; aPTT: ≤ 1.5 x ULN, unless the participant is receiving anticoagulant therapy
6. *Note: All screening laboratory tests must be reviewed by the investigator and be acceptable prior to enrollment. ALT = alanine aminotransferase; ANC = absolute neutrophil count; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; INR = international ratio; PT = prothrombin time; ULN = upper limit of normal

Exclusion criteria 5

1. Medical Conditions/History MC5. Meet any of the following criteria for cardiovascular disease: Symptomatic cardiac or cerebrovascular disease; cerebral vascular accident/stroke/myocardial infarction or unstable angina pectoris or any other deep arterial thromboembolic events within 6 months of randomization. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). New York Heart Association (NYHA) Class II or greater congestive heart failure or known left ventricular ejection fraction less than 40%.
2. MC7. History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment (eg, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs), any history of noninfectious enteritis or colitis requiring treatment with corticosteroids, or any history of inflammatory bowel disease (including Crohn’s disease or ulcerative colitis) or Celiac disease. Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment as listed above.
3. MC8. History of (noninfectious) pneumonitis/interstitial lung disease or current pneumonitis/ interstitial lung disease, including: Radiation pneumonitis requiring steroids. Active or recurrent pneumonitis/interstitial lung disease of any etiology.
4. MC9. 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
5. PT3. Prior treatment with: Trifluridine-tipiracil, regorafenib, or fruquitinib. Any immuno-oncology therapy (including anti– programmed cell death ligand 1 [PD (L)1], anti- cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], regulatory T cell (Treg) cell modifying agents, anti-programmed cell death ligand 2, anti- clusters of differentiation 137 (CD137), anti OX 40, anti- clusters of differentiation 40 (CD40), or any other immune checkpoint inhibitor). 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. Participants 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 6

1. DOR is measured from the time of 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.
2. PFS is 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.
3. OS is length of time from randomization until the date of death from any cause.
4. The incidence, severity, seriousness, and relatedness of treatment-emergent adverse events (TEAEs) and incidence and severity of clinical laboratory abnormalities graded according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
5. Serum concentration of DEN and estimated PK parameters (eg, Cmax and AUCall)
6. Percentage of treatment-emergent DEN ADA positive and ADA negative participants

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 9

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 7

Locations

3 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 50 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications