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

Lilly

Status and phase: Completed; Phase 1

Conditions: Solid Tumor

Treatments: Drug: Durvalumab; Drug: Tremelimumab; Drug: LY3022855

Study type: Interventional

Funder types: Industry

Identifiers

NCT02718911

I5F-MC-JSCC (Other Identifier)

2016-000427-11 (EudraCT Number)

16348

Details and patient eligibility

About

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.

Enrollment: 72 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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72 participants in 3 patient groups

LY3022855 + Durvalumab (Dose Escalation)

Experimental group

Description:

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.

Treatment:

Drug: LY3022855

Drug: Durvalumab

LY3022855 + Tremelimumab (Dose Escalation)

Experimental group

Description:

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.

Treatment:

Drug: LY3022855

Drug: Tremelimumab

LY3022855 + Durvalumab (Expansion)

Experimental group

Description:

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.

Treatment:

Drug: LY3022855

Drug: Durvalumab