LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Novartis Pharmaceuticals106 enrolled

Overview

The purpose of this signal seeking study was to determine whether treatment with LEE011 demonstrates sufficient efficacy in CDK4/6 pathway activated solid tumors and/or hematologic malignancies to warrant further study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

106

Conditions

Tumors With CDK4/6 Pathway Activation

Interventions

LEE011DRUG

Study drug was provided in 200 mg and 50 mg hard gelatin capsules to be taken orally

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient had a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative was included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma). * Patient must have been pre-identified as having a tumor with CDK4 amplification or mutation, CDK6 amplification or mutation, Cyclin D1 (CCND1) amplification, Cyclin D3 (CCND3) amplification, or p16 (CDKN2A) mutation * Patient had received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission. * Patient had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines. * Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Exclusion Criteria: * Patients had received prior treatment with LEE011. * Patient had clinically significant resting bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \> 109 msec, or QTcF \> 450 msec. * Patients had primary CNS tumor or CNS tumor involvement * Patient had received chemotherapy or anticancer therapy ≤ 4 weeks prior to starting study drug

Locations (61)

Outcomes

Primary Outcomes

Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments

Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS

Time frame: Baseline up ≥16 weeks up to approximately 36 months

Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS

CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS

Time frame: Baseline and ≥ 16 weeks up to approximately 36 months

Overall Response Rate (ORR) ≥ 16 Weeks. FAS

ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS

Data from ClinicalTrials.gov

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Birmingham, Alabama, United States

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Anchorage, Alaska, United States

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Little Rock, Arkansas, United States

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University of California Davis Cancer Center UC Davis Cancer (3)

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Danbury Hospital

Danbury, Connecticut, United States

Yale University School of Medicine Smilow Cancer Hospital

New Haven, Connecticut, United States

Whittingham Cancer Center Norwalk Hospital

Norwalk, Connecticut, United States

...and 51 more locations

Secondary Outcomes

Progression Free Survival (PFS)

Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progressive disease is defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression)

Time frame: Every 8 weeks until death, assessed up to 24 months

Overall Survival (OS)

Number of participants Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.

Time frame: Baseline up to approximately 36 months

Number of Days for Duration of Response for Responders

Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause. For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR.

Time frame: Baseline up to approximately 36 months