A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors

A Phase 1a/1b Trial Investigating the CSF-1R Inhibitor LY3022855 in Combination With Durvalumab (MEDI4736) or Tremelimumab in Patients With Advanced Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: LY3022855; Drug: Durvalumab; Drug: Tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
  • Wilrijk, Belgium, 2610
    • GZA St Augustinus
• Czechia
  • Czech Republic
    • Brno, Czech Republic, Czechia, 656 53
      • Masarykuv Onkology Institute
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Hadassah Medical Center
  • Ramat Gan, Israel, 5262000
    • Sheba Medical Center
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center Emory University
  • New York
    • New York, New York, United States, 10016
      • New York University Medical Center
    • New York, New York, United States, 10032
      • Columbia University College of Phys & Surgeons
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3022855 + Durvalumab (Dose Escalation); Cohort D1A: LY3022855 (25 mg,QW)+Durvalumab (750mg,Q2W): 25 mg LY3022855 administered once weekly (QW) intravenously (IV) in combination with 750 mg durvalumab administered every 2 weeks (Q2W) IV. Treatment may continue until disease progression or discontinuation. Cohort D2A: LY3022855 (50 mg,QW)+Durvalumab (750mg,Q2W) 50 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg durvalumab administered Q2W IV. Treatment may continue until disease progression or discontinuation. Cohort D3A: LY3022855 (75 mg,QW)+Durvalumab (750mg,Q2W) 75 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg durvalumab administered Q2W IV. Treatment may continue until disease progression or discontinuation. Cohort D4A: LY3022855 (100 mg,QW)+Durvalumab (750mg,Q2W) 100 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg durvalumab administered Q2W IV. Treatment may continue until disease progression or discontinuation.	Drug: LY3022855; Administered IV; Drug: Durvalumab; Administered IV; Other Names: MEDI4736
Experimental: LY3022855 + Tremelimumab (Dose Escalation); Cohort T1A: LY3022855 (50 mg,QW) +Tremelimumab (75mg,Q4W): 50 mg LY3022855 administered QW intravenously (IV) in combination with 75 mg tremelimumab administered every 4 weeks (Q4W) IV. Treatment may continue until disease progression or discontinuation. Cohort T2A: LY3022855 (100 mg,QW) +Tremelimumab (75mg,Q4W) 100 mg LY3022855 administered QW intravenously (IV) in combination with 75 mg tremelimumab administered Q4W IV. Treatment may continue until disease progression or discontinuation. Cohort T3A: LY3022855 (100 mg,QW) +Tremelimumab (225 mg,Q4W) 100 mg LY3022855 administered QW intravenously (IV) in combination with 225 mg tremelimumab administered Q4W IV. Treatment may continue until disease progression or discontinuation. Cohort T4A: LY3022855 (100 mg,QW) +Tremelimumab (750 mg,Q4W) 100 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg tremelimumab administered Q4W IV. Treatment may continue until disease progression or discontinuation.	Drug: LY3022855; Administered IV; Drug: Tremelimumab; Administered IV
Experimental: LY3022855 + Durvalumab (Expansion); Cohort B-1: NSCLC LY3022855+ Durvalumab: 100 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg durvalumab administered Q2W IV. Treatment may continue until disease progression or discontinuation. Cohort B-1: OVARIAN LY3022855+ Durvalumab: 100 mg LY3022855 administered QW intravenously (IV) in combination with 750 mg durvalumab administered Q2W IV. Treatment may continue until disease progression or discontinuation.	Drug: LY3022855; Administered IV; Drug: Durvalumab; Administered IV; Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose of LY3022855 Combined With Durvalumab (Maximum Tolerated Dose [MTD])	Recommended Phase 2 dose of LY3022855 that could be safely administered in combination with Durvalumab was based on defined dose limiting toxicities (DLT) assessment and MTD definition. MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT.	Cycle 1 (4 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]	ORR was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of participants. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	Baseline through Measured Progressive Disease or Death (Up To 24 months)
Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]	DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.	Baseline through Measured Progressive Disease (Up To 24 months)
Number of Participants With Anti-LY3022855, Anti-Durvalumab or Anti-Tremelimumab Antibodies	Number of participants with positive Anti-LY3022855, Anti-Durvalumab or Anti-Tremelimumab Antibodies was summarized by cohorts.	Baseline through Follow-up (Up To 24 Months)
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3022855 in Combination With Either Durvalumab or Tremelimumab, and the Single-Dose	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3022855 in Combination with either Durvalumab or Tremelimumab, and the Single-Dose	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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: AstraZeneca
• Investigators: Study Director: 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), Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Helpful Links

• Click here for more information about this study: A Study of LY3022855 in Combination With Durvalumab or Tremelimumab in Participants With Advanced Solid Tumors

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2016
• Primary Completion (Actual): December 14, 2018
• Study Completion (Actual): December 14, 2018

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 21, 2016
• First Posted (Estimated): March 24, 2016

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab
• Other Study ID Numbers: 16348; I5F-MC-JSCC (Other Identifier: Eli Lilly and Company); 2016-000427-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO