Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
- Registration Number
- NCT05007782
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This is a first-in-human (FIH) study to evaluate the safety and tolerability and to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of denikitug (also known as GS-1811) as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.
This study will be conducted in 6 parts (Parts A, B, and E: monotherapy, Parts C and D: combination therapy, and Part F for both monotherapy and combination therapy) in participants with advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or in participants with select solid tumors.
- Detailed Description
Part D allocation for 1 cohort will be randomized.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 376
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Disease:
- Part A: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
- Part B: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
- Part C: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatments known to confer clinical benefit or whose disease is indicated for anti- programmed cell death protein 1 or programmed cell death ligand 1 (PD-[L]1) monoclonal antibody monotherapy.
- Part D: Individuals with pathologically confirmed select advanced solid tumors.
- Part E: Individuals with pathologically confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatment known to confer clinical benefit.
- Part F: Individuals with pathologically-confirmed select advanced solid tumors. Participants must have received, have been intolerant to, or have been ineligible for all treatments known to confer clinical benefit; or, for participants who will undergo combination therapy, have disease which is indicated for anti-PD-(L)1 mAb monotherapy.
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Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 for individuals in Parts A, B, and C, and 0 or 1 for individuals in Parts D, E, and F.
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Adequate organ function.
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Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
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Tissue requirement:
- Parts A, C, D, E and F: Must provide pre-treatment adequate tumor tissue sample prior to enrollment.
- Part B and select participants in Parts C and F: Must have fresh pre-treatment and on-treatment biopsies for biomarker analysis.
Key
- Concurrent anticancer treatment.
- Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days).
- Any prior CCR8 directed therapy.
- Prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Exception: prior corneal transplant without requirement for systemic immunosuppressive agents is allowed.
- Concurrent active malignancy other than nonmelanoma skin cancer, curatively resected carcinoma in situ, localized prostate cancer, or superficial bladder cancer after undergoing potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease-free for > 2 years.
- History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
- History of autoimmune disease or active autoimmune disease requiring systemic treatment within 2 years.
- History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
- Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires IV antibiotics.
- Active hepatitis B virus (HBV) and/or hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
- Positive serum pregnancy test or breastfeeding female.
- Live vaccines within 30 days prior to first dose.
- Significant cardiovascular disease.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part C: Denikitug + Zimberelimab Dose Escalation Zimberelimab - Part D: Denikitug + Zimberelimab Dose Expansion Denikitug - Part D: Denikitug + Zimberelimab Dose Expansion Zimberelimab - Part E: Denikitug Monotherapy Dose Expansion Denikitug - Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule Denikitug - Part F: Denikitug Monotherapy and In Combination With Zimberelimab In Select Dose and Schedule Zimberelimab - Part A - Denikitug Dose Escalation Denikitug - Part C: Denikitug + Zimberelimab Dose Escalation Denikitug - Part B - Mandatory Paired Tumor Biopsy Denikitug -
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0 First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days 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 to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C Day 1 Through Day 21
- Secondary Outcome Measures
Name Time Method Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days Objective response rate (ORR) in Part D Day 1 Up to End of Treatment (24 months) Objective response rate is defined as the proportion of participants who achieve complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Disease control rate (DCR) Day 1 Up to End of Treatment (24 months) Disease control rate is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1
Time to response (TTR) Day 1 Up to End of Treatment (24 months) Time to response is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the first documentation of CR or PR that is subsequently confirmed
Duration of response (DOR) Day 1 Up to End of Treatment (24 months) Duration of response is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of definitive progressive disease (PD) or death from any cause, if applicable.
Progression-free survival (PFS) Day 1 Up to End of Treatment (24 months) Progression-free survival is defined as the time from the first dose of Denikitug in combination with Zimberelimab to the earlier of the first documentation of definitive PD or death from any cause
Trial Locations
- Locations (25)
University of California San Diego
🇺🇸La Jolla, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Smilow Cancer Center
🇺🇸New Haven, Connecticut, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center
🇪🇸Madrid, Spain
NEXT Oncology
🇺🇸San Antonio, Texas, United States
University of Wisconsin Clinical Sciences Center
🇺🇸Madison, Wisconsin, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
University Health Network, Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
Hospital Universitari Vall d´Hebrón
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Chi Mei Hospital, Liouying
🇨🇳Tainan City, Taiwan
National Taiwan University Cancer Center (NTUCC)
🇨🇳Taipei City, Taiwan
Taipei Tzu Chi General Hospital
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan City, Taiwan