Clinical trial NCT06532565: Study of GS-2121 Given Alone or in Combination in Adults With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of GS-2121 as Monotherapy and in Combination in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2024-08-01
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The main goal of this first-in-human (FIH) study is to learn about the safety and dosing of GS-2121 when given alone or in combination with zimberelimab (ZIM) in participants with advanced solid tumors.

The primary objectives of this study are:

* To assess the safety and tolerability of GS-2121 as monotherapy and GS-2121 in combination with zimberelimab in participants with advanced solid tumors.
* To identify the maximum tolerated dose (MTD) / maximum administered dose (MAD) and/or the recommended phase 2 dose (RP2D) of GS-2121 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.


Eligibility criteria: Key Inclusion Criteria:

* Participants diagnosed with histologically or cytologically confirmed advanced solid tumors who have progressed despite standard therapy, are intolerant to standard therapy, or are ineligible for standard therapy.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
* Tissue requirements:

  1. Parts A-D: Pretreatment tumor tissue is required.
  2. Parts A and C backfill cohorts: Participants must agree to fresh pre- and on-treatment biopsies.
* Adequate organ function.

Key Exclusion Criteria:

* Positive serum pregnancy test or participant who is breastfeeding.
* Requirement for ongoing therapy with any prohibited medications.
* Any anti-cancer therapy, whether investigational or approved within protocol specified time prior to initiation of study including: major surgery (\<4 weeks), experimental therapy (\<21 days or \<5 half-lives whichever is longer), approved immunotherapy or biologic therapy (\<28 days), approved chemotherapy (\<21 days or \<42 days for mitomycin or nitrosoureas), approved targeted small molecule therapy (\<14 days or \<5 half-lives whichever is longer), hormonal therapy or other adjunctive therapy for cancers other than cancer under evaluation in this study (\<14 days) or radiation therapy (\<21 days).
* Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
* Have not recovered (ie, returned to Grade 1 or baseline) from AEs due to a previously administered agent.
* Have known active central nervous system (CNS) metastases and/or leptomeningeal disease (LMD).
* Diagnosis of immunodeficiency, either primary or acquired.
* History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment.
* Have an active second malignancy.
* Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires systemic antibiotics, antifungals, or antivirals, respectively.
* History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
* Ascites or pleural effusion that is symptomatic and/or requiring medical intervention.
* Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV.
* Meet any of the following criteria for cardiac disease: Myocardial infarction or unstable angina pectoris within 6 months of enrollment. 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). Mean QT interval corrected for heart rate using the Fridericia's formula (QTcF) ≥ 470 msec. New York Heart Association Class \> III congestive heart failure or known left ventricular ejection fraction \< 40%.
* Live vaccines within 28 days of initiation of study drug(s).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Parts A and B: Percentage of Participants with Adverse Events and Serious Adverse Events
timeFrame: First dose up to 90 days post last dose (up to approximately 118 weeks)
measure: Parts A and B: Percentage of Participants with Laboratory Abnormalities
timeFrame: First dose up to 90 days post last dose (up to approximately 118 weeks)
measure: Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs) During Dose Escalation
timeFrame: Day 1 up to Day 21
measure: Parts C and D: Percentage of Participants with Adverse Events and Serious Adverse Events
timeFrame: First dose up to 90 days post last dose (up to approximately 118 weeks)
measure: Parts C and D: Percentage of Participants with Laboratory Abnormalities
timeFrame: First dose up to 90 days post last dose (up to approximately 118 weeks)
measure: Part C: Percentage of Participants with DLTs During Dose Escalation
timeFrame: Day 1 up to Day 21
Secondary outcomes:
measure: Parts A and B: Plasma Concentration of GS-2121 and Active Metabolite
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts A and B: PK Parameter: AUC0-24 of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts A and B: PK Parameter: Cmax of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts A and B: PK Parameter: Tmax of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts C and D: Plasma Concentration of GS-2121 and Active Metabolite
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts C and D: PK Parameter: AUC0-24 of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts C and D: PK Parameter: Cmax of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
measure: Parts C and D: PK Parameter: Tmax of GS-2121
timeFrame: Predose and postdose up to end of treatment (up to 105 weeks)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: