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LEE011

Phase 1

Locally Advanced or Metastatic NRAS Mutant Melanoma | Small molecule | Oncology |Pfizer, Inc.|Last Updated: Dec 7, 2020

Target and mechanism

Molecular targetCDK6, CDK4
Target classInhibitor
ModalitySmall molecule

Also known as Ribociclib, ribociclib

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment102

FDA Designations

No designations recorded

Clinical trial landscape

LEE011 · 1 trial · 1 indication

Phase 1 1
NCT01781572A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant MelanomaLocally Advanced or Metastatic NRAS Mutant Melanoma
COMPLETED102 Analytics
PHASE1COMPLETED
A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma
Locally Advanced or Metastatic NRAS Mutant MelanomaUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Dose Limiting Toxicities (Phase Ib)
first 28 days of treatment

To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.

Objective Response Rate (ORR) (Phase II)
Approximately 12 months after the FPFV

ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.

Secondary Endpoints

Plasma Concentration-time Profile (AUCtau) of LEE011 (Phase Ib)
Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau) of MEK162 (Phase Ib)
Cycle 1 Day 1
Plasma Concentration-time Profile (AUCtau,ss) of LEE011 (Phase Ib)
For the 28-day schedule the steady-state parameter time frame was Cycle 1 Day 21, and for the 21-day schedule the steady-state parameter time frame was Cycle 1 Day 14
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Phase IbEXPERIMENTALThe phase Ib is the dose escalation part where successive cohorts of 3-6 newly enrolled patients receiving various dose pairs considering the recommendation from an adaptive BLRM incorporating the EWOC principle until MTD(s)/RP2D is defined. If multiple alternate dosing schedules are explored in parallel, the allocation of patients will proceed in an alternating fashion. Approximately 40 patients are expected to be treated during the phase Ib part of the study. Dosing Schedule 1: MEK162 administered orally twice daily on a continuous dosing schedule. LEE011 administered orally once daily for 21 days followed by a 1 week break (28-day cycle). Dosing Schedule 2: MEK162 administered orally twice daily and LEE011 administered orally once daily for 3 weeks followed by a 1 week break (28-day cycle). Dosing Schedule 3: MEK162 administered orally twice daily and LEE011 administered once daily for 2 weeks followed by a 1 week break (21-day cycle).
Phase IIEXPERIMENTALThe Phase II part will begin once the MTD(s)/RP2D have been determined in the Phase Ib in order to assess antitumor activity of the LEE011and MEK162 combination. Patients enrolled in the Phase II part of the study are required to have measurable disease. Approximately 40 patients will be treated in this part. Phase II part will begin at the RP2D on the chosen schedule in order to assess antitumor activity of the LEE011 and MEK162 combination.

Interventions

NameTypeDescription
LEE011DRUGLEE011 will be administered orally once daily
MEK162DRUGMEK162 will be administered orally twice daily
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites17

Inclusion Criteria: * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. * Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients enrolled into the phase II expansion must have at least one measurable lesion as defined by RECI...

Countries:United StatesAustraliaGermanyItalyNetherlands
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Frequently asked questions about LEE011

What is LEE011 used for?

LEE011 is an investigational small molecule being studied for the treatment of locally advanced or metastatic NRAS mutant melanoma. It is a cyclin-dependent kinase (CDK) inhibitor, belonging to the -ciclib class of drugs. As of the available data, it is in Phase 1 clinical development.

What does LEE011 target?

LEE011 targets cyclin-dependent kinases (CDKs), as it belongs to the -ciclib class of CDK inhibitors. By inhibiting these kinases, it aims to interfere with cell cycle progression in cancer cells. This mechanism is being explored in the context of NRAS mutant melanoma.

Who makes LEE011?

LEE011 is being developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol PFE. The drug is also known as ribociclib.

What phase is LEE011 in?

LEE011 is in Phase 1 clinical development. It has completed one Phase 1 trial, which was a Phase Ib/II study. The drug is investigational and has not been approved by regulatory authorities for any indication.

What clinical trials is LEE011 in?

LEE011 has been studied in one clinical trial, identified as NCT01781572. This was a Phase Ib/II study of LEE011 in combination with MEK162 in patients with NRAS mutant melanoma. The trial has been completed and enrolled 102 participants across the United States, Australia, Germany, Italy, and the Netherlands.

Is LEE011 the same as ribociclib?

Yes, LEE011 is also known as ribociclib. Both names refer to the same investigational drug being developed by Pfizer for the treatment of locally advanced or metastatic NRAS mutant melanoma.