Clinical trial NCT05007782: Study of GS-1811 Given Alone or With Zimberelimab in Adults With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of GS-1811, an Afucosylated Anti-CCR8 Monoclonal Antibody, as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2021-08-16
Enrollment: 376
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: 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.

Eligibility criteria: Key Inclusion Criteria:

* 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.
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* 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.
* Adequate organ function.
* Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.
* 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 Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) in Part A and C
timeFrame: Day 1 Through Day 21
measure: Percentage of Participants Experiencing Adverse Events (AEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
timeFrame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: Percentage of Participants Experiencing Laboratory Abnormalities According to the NCI CTCAE v5.0
timeFrame: First dose to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax) for Denikitug
timeFrame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: PK Parameter: Minimum Observed Concentration (Cmin) for Denikitug
timeFrame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: PK Parameter: Time of Maximum Observed Concentration (Tmax) for Denikitug
timeFrame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: PK Parameter: Area Under the Concentration-time Curve (AUC) for Denikitug
timeFrame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: Percentage of Participants who Developed Antidrug Antibody (ADA) Against Denikitug
timeFrame: Day 1 Up to End of Treatment (up to 12 months for monotherapy and 24 months for combination therapy) plus 90 days
measure: Objective response rate (ORR) in Part D
timeFrame: Day 1 Up to End of Treatment (24 months)
measure: Disease control rate (DCR)
timeFrame: Day 1 Up to End of Treatment (24 months)
measure: Time to response (TTR)
timeFrame: Day 1 Up to End of Treatment (24 months)
measure: Duration of response (DOR)
timeFrame: Day 1 Up to End of Treatment (24 months)
measure: Progression-free survival (PFS)
timeFrame: Day 1 Up to End of Treatment (24 months)
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: New Haven
country: United States
facility: Smilow Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Clinical Sciences Center
state: Wisconsin
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: University Health Network, Princess Margaret Cancer Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebrón
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Tainan City
country: Taiwan
facility: Chi Mei Hospital, Liouying
city: Taipei City
country: Taiwan
facility: National Taiwan University Cancer Center (NTUCC)
city: Taipei City
country: Taiwan
facility: Taipei Tzu Chi General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Medical Foundation Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: