Delving into the Latest Updates on LY-3022855 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-CSF-1R-monoclonal-antibody-ImClone

+ [1]

Target

CSF-1R

Action

antagonists

Mechanism

CSF-1R antagonists(Colony stimulating factor 1 receptor antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication

Pancreatic Ductal Adenocarcinoma

Inactive Indication

Advanced Malignant Solid NeoplasmLocally Advanced MelanomaNon-Small Cell Lung Cancer

Originator Organization

Eli Lilly & Co.

Active Organization

Eli Lilly & Co.

Merck Sharp & Dohme Corp.

Inactive Organization-

Drug Highest PhaseEarly Phase 1

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 177912VH

Sequence Code 66219CDR3-L

Sequence Code 177917VL

Sequence Code 2266CDR2-L

Sequence Code 177898CDR1-L

Sequence Code 2173CDR2-H

Sequence Code 2657CDR1-H

Sequence Code 177893CDR3-H

BRAF/MEK targeted therapies and immune checkpoint inhibition have dramatically improved disease control and survival of patients with advanced melanoma. However, most patients do not have durable benefit from either of these therapies. BRAF targeted therapy often has a limited duration of efficacy due to the development of resistance. Pre-clinical data suggest that one possible way to overcome resistance to BRAF/MEK targeted therapy may be the addition of CSF1R inhibition. In this phase I/II study we evaluated the safety and efficacy of LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody in combination with the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib in patients with BRAF V600^E/K mutant metastatic melanoma. The trial was terminated early due to discontinuation of the development program for LY3022855 by the sponsor. Between August 2017 and May 2018 five pts were enrolled. Three patients experienced grade 3 events that were deemed possibly related to LY3022855. There were no grade 4 or grade 5 events related to LY3022855. One of the 5 patients had a complete response (CR), whereas the other 4 had progressive disease (PD). Median progression free survival was 3.9 months (90% CI: 1.9-37.2 mos). CSF1R inhibition with LY3022855 in combination with BRAF/MEK inhibition with vemurafenib and cobimetinib was difficult to tolerate in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration.

01 Oct 2021·Investigational New DrugsQ3 · MEDICINE

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Q3 · MEDICINE

Article

Author: Cohen, Jonathan E ; Bauer, Todd M ; Falchook, Gerald S ; Wang, Judy S ; Obermannova, Radka ; Chapman, Sonya ; Sabari, Joshua ; Peeters, Marc ; Zhang, Wei ; Peterson, Daniel A ; Rottey, Sylvie ; Dirix, Luc Y ; Calderon, Boris ; Perets, Ruth ; Frommer, Ronnie Shapira ; Carvajal, Richard D

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

01 Aug 2021·Investigational New DrugsQ3 · MEDICINE

LY3022855, an anti–colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial

Q3 · MEDICINE

Article

Author: Szpurka, Anna M ; Kauh, John Sae Wook ; Carlsen, Michelle ; Wesolowski, Robert ; Dowlati, Afshin ; Quinlan, Tonya ; Chapman, Sonya C ; Harvey, R Donald ; Yu, Danni ; Klempner, Samuel J ; Peterson, Daniel A ; Hamid, Omid ; Carvajal, Richard D

Background Tumor-associated macrophages (TAMs) promote tumor growth, metastasis, and therapeutic resistance via colony-stimulating factor-1 (CSF-1), acting through CSF-1 receptor (CSF-1R) signaling. This phase 1 study determined the safety, tolerability, pharmacokinetics-pharmacodynamics, immunogenicity, and efficacy of the anti-CSF-1R antibody LY3022855 in solid tumors. Methods Patients with advanced solid tumors refractory to standard therapy were enrolled and treated in 2 dosing cohorts: weight-based (part A) and non-weight-based (part B). Part A patients were assigned to intravenous (IV) dose-escalation cohorts: 2.5 mg/kg once per week (QW), 0.3 mg/kg QW, 0.6 mg/kg QW, 1.25 mg/kg once every 2 weeks (Q2W) and 1.25 mg/kg QW doses of LY3022855. Non-weight-based doses in part B were 100 mg and 150 mg IV QW. Results Fifty-two patients (mean age 58.6 ± 10.4 years) were treated with ≥1 dose of LY3022855 (range: 4-6). Five dose-limiting toxicities (left ventricular dysfunction, anemia, pancreatitis, rhabdomyolysis, and acute kidney injury) occurred in 4 patients. The non-weight-based 100 mg QW dose was established as the RP2D. The most common treatment-emergent adverse events were increase in liver function variables, fatigue, nausea, vomiting, diarrhea, anorexia, pyrexia, increased lipase, amylase, and lactate dehydrogenase. Clearance decreased with increasing dose and weight-based dosing had minimal effect on pharmacokinetics. Serum CSF-1, and IL-34 levels increased at higher doses and more frequent dosing, whereas TAMs and CD14dimCD16bright levels decreased. Three patients achieved stable disease. No responses were seen. Conclusions LY3022855 was well tolerated and showed dose-dependent pharmacokinetics-pharmacodynamics and limited clinical activity in a heterogenous solid tumor population. ClinicalTrials.gov ID NCT01346358 (Registration Date: May 3, 2011).

100 Deals associated with LY-3022855

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Ductal Adenocarcinoma	Phase 1	United States	Merck Sharp & Dohme Corp.	27 Sep 2018
Pancreatic Ductal Adenocarcinoma	Phase 1	United States	Eli Lilly & Co.	27 Sep 2018
Locally Advanced Melanoma	Phase 1	United States	Eli Lilly & Co.	06 Jun 2017
Non-Small Cell Lung Cancer	Phase 1	Czechia	Eli Lilly & Co.	16 Jun 2016
Non-Small Cell Lung Cancer	Phase 1	Israel	Eli Lilly & Co.	16 Jun 2016
Non-Small Cell Lung Cancer	Phase 1	United States	Eli Lilly & Co.	16 Jun 2016
Non-Small Cell Lung Cancer	Phase 1	Belgium	Eli Lilly & Co.	16 Jun 2016
Advanced Malignant Solid Neoplasm	Phase 1	United States	Eli Lilly & Co.	15 Jun 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02265536 (CTgov)	Phase 1	Neoplasms	34	LY3022855 (LY3022855 - 1.25 mg/kg Q2W Breast Cancer)	vmuoqgnqvi(brwzxllsxe) = xnclcvzdgt tmcgzibjnj (yhnuuxvqnl, vdzillvpvf - trijieqfar) View more	-	28 Oct 2024
NCT02265536 (CTgov)	Phase 1	Neoplasms	34	LY3022855 (LY3022855 - 1.0 mg/kg WK1_2_4_5 Breast Cancer)	vmuoqgnqvi(brwzxllsxe) = mtocukwwvp tmcgzibjnj (yhnuuxvqnl, lbwmtcocvd - tkvknzhven) View more	-	28 Oct 2024
NCT03153410 (CTgov)	Early Phase 1	Pancreatic adenocarcinoma \| Pancreatic Ductal Adenocarcinoma	11	IMC-CS4+cyclophosphamide+GVAX Pancreas Vaccine (GVAX)+pembrolizumab+GVAX	tnrdlisuxa(lujzdjjojz) = vzqlttbxzj peqmhyokhh (qiagwmidkr, umuptrvypu - ovdkoepvzp) View more	-	15 Oct 2024
NCT03101254 (CTgov)	Phase 1/2	Melanoma \| Locally Advanced Melanoma	5	LY3022855+Cobimetinib+Vemurafenib	njcrkwmqih(sxbuqzaaci) = iccnpbqwyv zkxjtqxmlo (ybranbuqxt, jzvamonuna - ydggpzbore) View more	-	17 Jul 2024
NCT02718911 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	72	durvalumab+tremelimumab+LY3022855	(neluoxxtqi) = maximum tolerated dose was not reached jhifovshyx (pwbxozcpqs ) View more	Positive	01 Oct 2021
NCT02718911 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	72	durvalumab+LY-3022855		Positive	01 Oct 2021
NCT01346358 (Pubmed \| Invest New Drugs) Manual	Phase 1	Solid tumor	52	LY3022855	(nmmxypjwkx) = The non-weight-based 100 mg QW dose was established as the RP2D. tckjywjxui (iionkxvjhk ) View more	Negative	01 Aug 2021
NCT01346358 (ASCO2017)	Phase 1	HR-positive/HER2-low Solid Tumors	35	LY3022855	(mroeeridvb) = vquorqjrii pxjkqofpll (sclsviqgse ) View more	-	30 May 2017

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Biosimilar

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