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

NCT02718911 | Completed Phase 1 Results

• 3 other identifiers: 16348I5F-MC-JSCC2016-000427-11
• Study Type: interventional
• Target: 72
• Locations: 4 countries
• Sites: 14

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

  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)]

  Baseline through Measured Progressive Disease (Up To 24 months)

• Number of Participants With Anti-LY3022855, Anti-Durvalumab or Anti-Tremelimumab Antibodies

  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

  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

Study Arms (3)

LY3022855 + Durvalumab (Dose Escalation)

EXPERIMENTAL

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; Drug: Durvalumab

LY3022855 + Tremelimumab (Dose Escalation)

EXPERIMENTAL

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; Drug: Tremelimumab

LY3022855 + Durvalumab (Expansion)

EXPERIMENTAL

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; Drug: Durvalumab

Interventions

LY3022855 DRUG

Administered IV

LY3022855 + Durvalumab (Dose Escalation); LY3022855 + Durvalumab (Expansion); LY3022855 + Tremelimumab (Dose Escalation)

Durvalumab DRUG

Administered IV

Also known as: MEDI4736

LY3022855 + Durvalumab (Dose Escalation); LY3022855 + Durvalumab (Expansion)

Tremelimumab DRUG

Administered IV

LY3022855 + Tremelimumab (Dose Escalation)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead
• AstraZeneca: collaborator

Study Sites (14)

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Winship Cancer Center Emory University

Atlanta, Georgia, 30322, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Columbia University College of Phys & Surgeons

New York, New York, 10032, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

GZA St Augustinus

Wilrijk, 2610, Belgium

Location

Masarykuv Onkology Institute

Brno, Czech Republic, 656 53, Czechia

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Related Publications (1)

• 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.

  PMID: 33852104 DERIVED

Related 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

MeSH Terms

Interventions

LY3022855; durvalumab; tremelimumab

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 24, 2016
• Study Start: June 16, 2016
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: October 16, 2023
• Results First Posted: October 16, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); CZ (1); IL (3); US (7)