Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as LY3022855
IMC-CS4 · 4 trials · 4 indications
DLT is based on CTCAE v4.03. DLT refers to toxicities experienced during the first cycle of treatment that are possibly, probably, or definitely related to the study medication regimen, and grade or category outlined in protocol section 5.4.
See previous primary outcome measure for the DLT defination. A conventional algorithm (3+3 design) will be used to identify the MTD, escalating on 0/3 or 1/6 DLTs, and de-escalating if two DLTs are encountered. The MTD will be the highest dose level at which ≤ 1/6 subjects experience a DLT. If dose level 1 is discovered to be intolerable (with 2/3 or ≥ 2/6 subjects experiencing a DLT), the trial will be discontinued.
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.
The immunomodulatory activity of the drug was documented by examining markers that include, but are not limited to: Live-Dead, Cluster of Differentiation 3 (CD3), CD4, CD8, CD14, CD16, Foxhead Box p3 (FoxP3), PD-1, Ki-67, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), Human Leukocyte Antigen-D-relate (HLA-DR), T-cell immunoglobulin and mucin-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and Inducible T-cell COStimulator (ICOS). The expression of these markers was quantified by flow cytometric analysis with an antibody panel.
The immunomodulatory activity of the drug was measured in participants with advanced, refractory breast or prostate cancers using serum cytokines. Serum cytokine levels was determined by MSD multiplex cytokine immunoassay technology or ELISA, and that may include but not be limited to Interleukin 6 (IL-6), IL-8, IL-10 and Tumor necrosis factor (TNF-α).
The immunomodulatory activity of the drug was measured in participants with advanced, refractory breast or prostate cancers using serum cytokines. Serum cytokines will be determined by MSD multiplex cytokine immunoassay or ELISA. The markers to be measured using these technologies include, but are not limited to: CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-34, and TNF-α.
Pharmacokinetics (PK) - Maximum concentration (Cmax) of IMC-CS4.
Pharmacokinetics - Minimum concentration (Cmin) of IMC-CS4.
Pharmacokinetics - Area Under the Curve (AUC) of IMC-CS4.
Pharmacokinetics - Volume of distribution at steady state (Vss) of IMC-CS4.
Pharmacokinetics -Clearance (Cl) of IMC-CS4.
| Arm | Type | Description |
|---|---|---|
| Phase I: Dose Level 1: LY3022855 (50mg) + Vemurafenib + Cobimetinib | EXPERIMENTAL | * Starting dose level of LY3022855 50mg IV administered intravenously every week * Vemurafenib 960 mg BID administered by mouth twice daily * Cobimetinib 60 mg administered by mouth once daily on days 1-21of each cycle |
| Phase I: Dose Level 2: LY3022855 (75mg) + Vemurafenib + Cobimetinib | EXPERIMENTAL | * LY3022855 50mg IV administered intravenously every week * Vemurafenib 960 mg BID administered by mouth twice daily * Cobimetinib 60 mg administered by mouth once daily on days 1-21of each cycle |
| Phase I: Dose Level 3: LY3022855 (100mg) + Vemurafenib + Cobimetinib | EXPERIMENTAL | * LY3022855 100mg IV administered intravenously every week * Vemurafenib 960 mg BID administered by mouth twice daily * Cobimetinib 60 mg administered by mouth once daily on days 1-21of each cycle |
| Phase II: LY3022855 (MTD) + Vemurafenib + Cobimetinib | EXPERIMENTAL | * MTD of LY3022855 was not established * Vemurafenib planned 960 mg BID administered by mouth twice daily * Cobimetinib planned 60 mg administered by mouth once daily on days 1-21of each cycle |
| 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. |
| 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. |
| 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. |
| LY3022855 1.25 mg/kg Q2W | EXPERIMENTAL | 1.25 milligram per kilogram (mg/kg) LY3022855 administered intravenously (IV), once every two weeks (Q2W). Treatment is 6 week cycle. Participants may receive multiple cycles if they are deriving clinical benefit. |
| LY3022855 1.0 mg/kg WK1_2_4_5 | EXPERIMENTAL | 1.0 mg/kg LY3022855 administered IV on Weeks 1, 2, 4, and 5 of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit. |
| LY3022855 100 mg Q2W | EXPERIMENTAL | 100 mg of LY3022855 administered IV once every two weeks of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit. |
| LY3022855 100 mg QW | EXPERIMENTAL | 100 mg of LY3022855 administered IV. once a week (QW) of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit. |
| IMC-CS4 Weight Based Dosing | EXPERIMENTAL | Participants received 2.5 mg/kg once weekly (QW), 0.3 mg/kg QW, 0.6 mg/kg QW, 1.25 mg/kg every two weeks (Q2W) and1.25 mg/kg QW of IMC CS4 by intravenous infusion in Part A. |
| IMC-CS4 Non-Weight Based Dosing | EXPERIMENTAL | Participants received 100 mg QW, 100 mg QW on weeks 1, 2, 4 and 5 and 150 mg QW of IMC CS4 by intravenous infusion in Part B. |
| Name | Type | Description |
|---|---|---|
| LY3022855 | DRUG | LY3022855 is a colony-stimulating factor-1 receptor (CSF-1R) inhibitor |
| Vemurafenib | DRUG | Vemurafenib is a BRAF inhibitor that works by blocking altered BRAF proteins from stimulating the growth of melanoma cancer cells |
| Cobimetinib | DRUG | Cobimetinib works by blocking a protein called MEK that has been known to promote melanoma growth |
| Durvalumab | DRUG | Administered IV |
| Tremelimumab | DRUG | Administered IV |
| IMC-CS4 | BIOLOGICAL | - |
Inclusion Criteria: * For enrollment to the phase I portion: participants must have a histologically confirmed melanoma with a BRAF V600E or BRAF V600K mutation (identified via NextGen sequencing using the DFCI/BWH OncoPanel or any CLIA-certified method) that is metastatic or unresectable and for w...
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IMC-CS4 is an investigational monoclonal antibody being developed by Eli Lilly and Company for the treatment of neoplasms, specifically advanced solid tumors. It is in Phase 1 clinical development and has been studied in a single completed trial. It is not an approved therapy.
IMC-CS4 targets CSF1R, the colony stimulating factor 1 receptor. It is classified as an inhibitor of this receptor. Targeting CSF1R is intended to affect signaling pathways associated with tumor-associated macrophages in the tumor microenvironment, which is the rationale for its study in advanced solid tumors.
IMC-CS4 is developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. Lilly is the sponsor of the clinical program evaluating the antibody in patients with advanced solid tumors.
IMC-CS4 is in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA. The Phase 1 program consists of one completed trial, with no active trials currently listed.
IMC-CS4 has been evaluated in the Phase 1 trial NCT01346358, titled A Study of IMC-CS4 in Subjects With Advanced Solid Tumors. That trial enrolled 52 participants with neoplasms across sites in the United States, included adults 18 years and older of all sexes, and is now completed.