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

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02718911
• Other study ID #: 16348
• Secondary ID: I5F-MC-JSCC2016-
• Status: Completed
• Phase: Phase 1
• Start date: June 16, 2016
• Est. completion date: December 14, 2018

Study information

• Verified date: October 2023
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 14, 2018
• Est. primary completion date: December 14, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 10?/Liters (L) (1500/cubic millimeters)

• Platelet count = 100 x 10?/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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• LY3022855
Administered IV
• Durvalumab
Administered IV
• Tremelimumab
Administered IV

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	GZA St Augustinus	Wilrijk
Czechia	Masarykuv Onkology Institute	Brno	Czech Republic
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Sheba Medical Center	Ramat Gan
United States	Winship Cancer Center Emory University	Atlanta	Georgia
United States	Sarah Cannon Research Institute at HealthOne	Denver	Colorado
United States	Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Columbia University College of Phys & Surgeons	New York	New York
United States	New York University Medical Center	New York	New York
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	AstraZeneca

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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

External Links

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