Clinical trial NCT02718911: A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors
Official title: A Phase 1a/1b Trial Investigating the CSF-1R Inhibitor LY3022855 in Combination With Durvalumab (MEDI4736) or Tremelimumab in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2016-03-24
Enrollment: 72
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 purpose of this study is to evaluate the safety of the colony-stimulating factor 1 receptor (CSF-1R) inhibitor LY3022855 in combination with durvalumab or tremelimumab in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Must have histological or cytological evidence of a diagnosis of cancer that is not amenable to curative therapy.
* Part B: Must have a type of malignancy that is being studied.
* Part A and Part B (ovarian cancer cohort only): Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies.
* Part A (all cohorts): Have the presence of measureable and /or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
* Part B (all cohorts): Have the presence of measurable disease as defined by the RECIST 1.1.
* Have adequate normal organ and marrow function, including the following:

  * Absolute neutrophil count ≥ 1.5 x 10⁹/Liters (L) (1500/cubic millimeters)
  * Platelet count ≥ 100 x 10⁹/L (≥100,000/cubic millimeters)
  * Hemoglobin ≥9 grams per deciliter or ≥5.6 millimoles per liter
  * Serum Creatinine ≤1.5 × institutional upper limit of normal (ULN)
  * Total bilirubin ≤1.5 × institutional ULN
  * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × institutional ULN OR ≤5 × institutional ULN for participants with liver metastases
  * International normalized ratio (INR) or prothrombin time (PT) INR ≤1.5 × institutional ULN or PT ≤5 seconds above institutional ULN
  * PTT or activated partial thromboplastin time (aPTT) ≤5 seconds above institutional ULN
  * Thyroid stimulating hormone (TSH) OR free thyroxine (T4) within the normal limits
* Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.

Exclusion Criteria:

* Are currently receiving or have had prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 milligrams/day of prednisone, or an equivalent corticosteroid.
* Have symptomatic central nervous system (CNS) malignancy or metastasis.
* Have had any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, have any unresolved irAE Grade \>1, or any irAE that led to the permanent discontinuation of prior immunotherapy.
* Have experienced a Grade ≥3 AE or a neurologic or ocular AE of any grade while receiving prior immunotherapy.

Primary outcomes:
measure: Recommended Phase 2 Dose of LY3022855 Combined With Durvalumab (Maximum Tolerated Dose [MTD])
timeFrame: Cycle 1 (4 weeks)
Secondary outcomes:
measure: Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
timeFrame: Baseline through Measured Progressive Disease or Death (Up To 24 months)
measure: Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]
timeFrame: Baseline through Measured Progressive Disease (Up To 24 months)
measure: Number of Participants With Anti-LY3022855, Anti-Durvalumab or Anti-Tremelimumab Antibodies
timeFrame: Baseline through Follow-up (Up To 24 Months)
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3022855 in Combination With Either Durvalumab or Tremelimumab, and the Single-Dose
timeFrame: Cycle 1 Day 1: 2 hours post End of Infusion (EOI), Day 2: 24-hour post EOI, Day 3: 48 hour post EOI; Cycle 2 Day 8: 2 h post-EOI, Day 9: 24 h post-EOI, Day 10: 48 h post-EOI
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthOne
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Center Emory University
state: Georgia
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: New York
country: United States
facility: Columbia University College of Phys & Surgeons
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Wilrijk
country: Belgium
facility: GZA St Augustinus
city: Brno
country: Czechia
facility: Masarykuv Onkology Institute
state: Czech Republic
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Falchook GS, Peeters M, Rottey S, Dirix LY, Obermannova R, Cohen JE, Perets R, Frommer RS, Bauer TM, Wang JS, Carvajal RD, Sabari J, Chapman S, Zhang W, Calderon B, Peterson DA. A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Invest New Drugs. 2021 Oct;39(5):1284-1297. doi: 10.1007/s10637-021-01088-4. Epub 2021 Apr 14.