NCT02159066|CompletedPhase 2Results

LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma

LOGIC-2

The LOGIC 2 Trial A Phase II, Multi-center, Open-label Study of Sequential LGX818/MEK162 Combination Followed by a Rational Combination With Targeted Agents After Progression, to Overcome Resistance in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma.

Pfizer ClinicalTrials.gov

Compare

3 other identifiers

CLGX818X2109C42210132013-004552-38

Study Type

interventional

Target

158

Locations

9 countries

Sites

Timeline

RegisteredJun 2014

StartedJul 2014

CompletionJan 2023

Brief Summary

The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

158

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Jul 2014

Longer than P75 for phase_2

Geographic Reach

9 countries

32 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

8.5 years study duration

First Submitted

Initial submission to the registry

April 28, 2014

Completed

1 month until next milestone

First Posted

Study publicly available on registry

June 9, 2014

Completed

1 month until next milestone

Study Start

First participant enrolled

July 23, 2014

Completed

8.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 10, 2023

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 10, 2023

Completed

1.2 years until next milestone

Results Posted

Study results publicly available

March 5, 2024

Completed

Last Updated

March 5, 2024

Status Verified

February 1, 2024

Enrollment Period

8.5 years

First QC Date

April 28, 2014

Results QC Date

December 27, 2023

Last Update Submit

February 6, 2024

Conditions

Melanoma

Keywords

Melanoma

Outcome Measures

Primary Outcomes (1)

Overall Response Rate (ORR): Part II
ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (\<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (\<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment.
From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)

Secondary Outcomes (43)

Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II
Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib)
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I
Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With AEs and SAEs: Part II
Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)
+38 more secondary outcomes

Study Arms (5)

LGX818 + MEK162

EXPERIMENTAL

Drug: LGX818Drug: MEK162

LGX818 + MEK162 + LEE011

EXPERIMENTAL

Drug: LEE011

LGX818 + MEK162 + BGJ398

EXPERIMENTAL

Drug: BGJ398

LGX818 + MEK162 + BKM120

EXPERIMENTAL

Drug: BKM120

LGX818 + MEK162 + INC280

EXPERIMENTAL

Drug: INC280

Interventions

LGX818DRUG

Combination of LGX818 and MEK162 (Part I)

LGX818 + MEK162

MEK162DRUG

Combination of LGX818 and MEK162 (Part I)

LGX818 + MEK162

LEE011DRUG

Combination of LGX818 + MEK162 + LEE011 (Part II)

LGX818 + MEK162 + LEE011

BGJ398DRUG

Combination of LGX818 + MEK162 + BGJ398 (Part II)

LGX818 + MEK162 + BGJ398

BKM120DRUG

Combination of LGX818 + MEK162 + BKM120 (Part II)

LGX818 + MEK162 + BKM120

INC280DRUG

Combination of LGX818 + MEK162 + INC280 (Part II)

LGX818 + MEK162 + INC280

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Age ≥ 18 years
Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer \[AJCC\])
Documented evidence of BRAF V600 mutation.
Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated.
Evidence of measurable disease, as determined by RECIST v1.1.

You may not qualify if:

Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs.
Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Novartis Medical Monitor. The brain metastasis must be either asymptomatic or treated and stable for at least 4 weeks and on a stable or tapering dose of steroids for at least 2 weeks. Patients with brain metastasis are not eligible for the combination with LEE011.
Known acute or chronic pancreatitis.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
Clinically significant cardiac disease including any of the following:
CHF requiring treatment (NYH grade ≥ 2),
LVEF \< 50% as determined by MUGA scan or ECHO
History or presence of clinically significant ventricular arrhythmias or atrial fibrillation
Clinically significant resting bradycardia
Unstable angina pectoris ≤ 3 months prior to starting study drug
Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug,
QTcF \> 480 msec. Patients with any of the following laboratory values at
Screening/baseline:
Absolute neutrophil count (ANC) \<1,500/mm3 \[1.5 x 109/L\]
Platelets \< 100,000/mm3 \[100 x 109/L\]
+18 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (32)

University of California Los Angeles

Los Angeles, California, 90024, United States

Location

Cancer Care Center