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LCL161

Phase 2

Breast Cancer | Small molecule | Oncology |Novartis AG|Last Updated: Dec 19, 2020

Success Probability

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Market & Valuation

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Trial Design

RandomizedACTIVE_CONTROLLED
Total Trials1
Total Enrollment209

FDA Designations

No designations recorded

Clinical trial landscape

LCL161 · 4 trials · 4 indications

Phase 2 1Phase 1 3
NCT01617668A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast CancerBreast Cancer
COMPLETED209 Analytics
PHASE2COMPLETED
A Randomized, Phase 2, Neoadjuvant Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer
Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy
12 weeks

pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on Bayesian design using a binomial distribution for the data with a beta prior. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). Median values are posterior medians of pCR rate for each group.

Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy
12 weeks

To assess the number of patients who experienced a pathological response in breast.

Difference in pCR Rates Between Treatment Arms
12 weeks

pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on the posterior distribution of the difference in pCR rates between the experimental and control arms of the study, within each gene expression signature group.The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval.

Frequency of dose limiting toxicities as a function of LCL161 during first cycle
First cycle (21 days)
Adverse events of oral LCL161
From informed consent until 28 days after end of treatment (end of treatment visit occurs within 7 days after the determination of study discontinuation)

Type and frequency of adverse events of oral LCL161 when administered in combination with weekly paclitaxel

Maximum tolerated dose (MTD)/RP2D of LCL161 when administered in combination with once weekly paclitaxel
24 months
Occurrence of dose-limiting toxicities
Cycle 1

Secondary Endpoints

Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors
12 weeks
Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors
12 weeks
pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status
12 weeks
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Paclitaxel with LCL161EXPERIMENTALPatients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LECL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm.
Paclitaxel without LCL161ACTIVE_COMPARATORPatients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm.
LCL161EXPERIMENTALDose escalation part: Eligible patients will start to receive oral LCL161 once a week and will receive weekly paclitaxel, at 80 mg/m2 intravenous infusion over 1 hour, in combination with LCL161 from cycle 2. Dose expansion part: Eligible patients will receive oral LCL161 at the maximum tolerated dose and/or recommended dose in combination with weekly paclitaxel, at 80 mg/m2 intravenous infusion over 1 hour from cycle 1.
LCL161 + PaclitaxelEXPERIMENTAL -
Weekly dosing of LCL161EXPERIMENTALby mouth (oral)
Comparison of LCL161EXPERIMENTALtablet versus liquid
Twice daily dosing of LCL161EXPERIMENTALby mouth for 4 days followed by a 3-day rest period every week

Interventions

NameTypeDescription
LCL161DRUGLCL161 was available as 300 mg, tablets, which was supplied in child-resistant bottles.
paclitaxelDRUGCommercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment. iv 80mg/m2
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Eligibility Criteria

Age Range18 Years to N/A
SexFEMALE
Healthy VolunteersNo
Study Sites50

Inclusion Criteria: * Histologically confirmed diagnosis of invasive triple negative breast cancer * Known status for the LCL161 predictive gene expression signature as determined during molecular pre-screening * Candidates for mastectomy or breast-conserving surgery * Primary tumor of greater than...

Countries:United StatesAustraliaBrazilCzechiaGermanyIrelandItalyRussiaSouth KoreaSpainTaiwanUnited KingdomJapanCanada
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Competitive Landscape -Breast Cancer 402 trials

Top 20 of 92 competitors

CompanyTickerTrialsLead PhaseDrugs
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant
BeOne Medicines Ltd. Sponsored ADRONC5PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib
Relay Therapeutics, Inc.RLAY2PHASE3Zovegalisib, Capivasertib, Fulvestrant
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam
Atossa Therapeutics, Inc.ATOS1PHASE2endoxifen, goserelin
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Frequently asked questions about LCL161

What is LCL161 used for?

LCL161 is an investigational small molecule being studied for the treatment of neoplasms, advanced solid tumors, breast cancer, and solid tumors. It is being developed by Novartis AG (NVS) and has been evaluated in clinical trials for these oncology indications.

How does LCL161 work?

LCL161 is a small molecule that targets inhibitors of apoptosis proteins (IAPs), which are proteins that help cancer cells survive. By inhibiting these proteins, LCL161 is designed to promote apoptosis, or programmed cell death, in tumor cells.

Who makes LCL161?

LCL161 is being developed by Novartis AG, a multinational pharmaceutical company headquartered in Basel, Switzerland. Novartis is publicly traded on the New York Stock Exchange under the ticker symbol NVS.

What phase is LCL161 in?

LCL161 has completed Phase 1 and Phase 2 clinical trials. The most advanced trial was a randomized Phase 2 neoadjuvant study in patients with triple negative breast cancer, which has been completed. LCL161 is not FDA approved and remains an investigational drug.

What clinical trials is LCL161 in?

LCL161 has been studied in four completed clinical trials. These include NCT01098838, a Phase 1 study in patients with advanced solid tumors; NCT01240655, a Phase 1 study combining LCL161 with weekly paclitaxel; NCT01617668, a Phase 2 neoadjuvant study in triple negative breast cancer; and NCT01968915, a Phase 1 study in Japanese patients with advanced solid tumors.

Is LCL161 the same as any other drug?

LCL161 is not known by any alternative names. It is a distinct investigational compound developed by Novartis AG for the treatment of various solid tumors and breast cancer.