Trial Outcomes & Findings for A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression (NCT NCT02300987)

Last Updated: 2020-10-26

Results Overview

Date of randomization to the date of the first documented progression or death due to any causeas per RECIST v1.1 (by local investigator assessment). Only includes data prior to cross over. Disease progression follow-up: Subjects who discontinued study drug for any reasons other than disease progression were followed for efficacy every 8 weeks during the first 12 months. After 12 months, they were followed for every 12 weeks until disease progression, death, discontinuation from the study for any other reason (i.e. loss to follow-up or withdrawal of consent), the initiation of a new antineoplastic treatment, or until all subjects had been followed for at least 18 months after their first dose of study drug, or early study termination, whichever occurred first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

At 24 months

Results posted on

2020-10-26

Participant Flow

Subjects were randomly assigned to Ribociclib or Placebo in a 2:1 ratio. The 2 subjects from the placebo group (primary phase) entered the secondary treatment phase (cross over) after they experienced disease progression, and were then treated with LEE01. One patient from the LEE arm entered the secondary treatment phase.

42 subjects were planned to be included (28 for the LEE011 arm and 14 for the Placebo arm). The study was stopped prematurely with 10 patients randomized and treated in this study (8 in the ribociclib arm, 2 in the placebo arm).

Participant milestones

Participant milestones
Measure	LEE011 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm 600 mg daily dosing days 1-21 of a 28 day cycle
Primary Phase : Prior to Cross-over STARTED	8	2
Primary Phase : Prior to Cross-over COMPLETED	2	0
Primary Phase : Prior to Cross-over NOT COMPLETED	6	2
Secondary Phase : Cross-over to LEE011 STARTED	1	2
Secondary Phase : Cross-over to LEE011 COMPLETED	0	1
Secondary Phase : Cross-over to LEE011 NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	LEE011 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm 600 mg daily dosing days 1-21 of a 28 day cycle
Primary Phase : Prior to Cross-over Withdrawal by Subject	1	0
Primary Phase : Prior to Cross-over Physician Decision	2	0
Primary Phase : Prior to Cross-over progressive disease	3	2
Secondary Phase : Cross-over to LEE011 Lack of Efficacy	1	0
Secondary Phase : Cross-over to LEE011 Adverse Event	0	1

Baseline Characteristics

full analysis set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Total n=10 Participants Total of all reporting groups
Age, Continuous	32.3 years STANDARD_DEVIATION 6.76 • n=5 Participants • full analysis set	40.5 years STANDARD_DEVIATION 17.68 • n=7 Participants • full analysis set	33.9 years STANDARD_DEVIATION 9.07 • n=5 Participants • full analysis set
Sex: Female, Male Female	0 Participants n=5 Participants • Ful analysis set	0 Participants n=7 Participants • Ful analysis set	0 Participants n=5 Participants • Ful analysis set
Sex: Female, Male Male	8 Participants n=5 Participants • Ful analysis set	2 Participants n=7 Participants • Ful analysis set	10 Participants n=5 Participants • Ful analysis set
Race/Ethnicity, Customized Caucasian	4 Participants n=5 Participants • Full analysis set	1 Participants n=7 Participants • Full analysis set	5 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized Native American	1 Participants n=5 Participants • Full analysis set	0 Participants n=7 Participants • Full analysis set	1 Participants n=5 Participants • Full analysis set
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants • Full analysis set	1 Participants n=7 Participants • Full analysis set	4 Participants n=5 Participants • Full analysis set

PRIMARY outcome

Timeframe: At 24 months

Population: Full analysis set. After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Progression Free Survival (PFS)	71.4 Days Interval 33.9 to 90.1	0.0 Days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: At 24 months

as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the subject who experienced SD as best overall response entered the secondary phase and was treated with LEE011 after he experienced progressive disease, following his best Stable Disease response. In this outcome measure 2, only the best overall response is indicated.

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Best Overall Response (BOR) Stable Disease (SD)	8 Participants	1 Participants
Best Overall Response (BOR) Progressive Disease (PD)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: At 27 months

Overall response rate (ORR) = complete response (CR) or partial response (PR). ORR was zero, as there were no CRs or PRs in either of the groups

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Overall Response Rate	0 percentage of participants Interval 0.0 to 36.9	0 percentage of participants Interval 0.0 to 84.2

SECONDARY outcome

Timeframe: At 24 months

as per RECIST v1.1. Only includes data prior to cross over. Placebo arm : the disease control rate is based on the best overall response described in the outcome measure 2.

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Disease Control Rate (DCR)	100 percentage of participants Interval 63.1 to 100.0	50 percentage of participants Interval 1.3 to 98.7

SECONDARY outcome

Timeframe: At 27 months

Only includes data prior to cross over. OS defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut off, OS was censored at the date of last known date patient alive

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Overall Survival (OS)	6 Participants Interval 27.6 to 92.5	1 Participants Interval 0.6 to 91.0

SECONDARY outcome

Timeframe: 1, 2, 3, 6, 9, 12, 15, 18, 21, 24 and 27 months

Population: Full analysis set.After 10 subjects were enrolled and treated, the recruitment was halted due to business reasons.There were no safety concerns which contributed to the decision to halt enrollment. Limited efficacy analyses were performed.

as per RECIST v1.1. Only includes data prior to cross over. Kaplan-Meier estimates (%) OS rate \[95% CI\] at different timepoints. The overall survival rate at 27 month is 72.9% by Kaplan-Meyer (K-M) estimator; the reason that it is not 75% (1-25%) (Overall survival) is because of censoring. When the other 6 patients were censored would impact the survival rate with K-M method as the number of patients at risk after each censor was changed. NA for the 95% CI is indicated when no patient died at the time of assessment, as the CI could not be calculated as per definition. Results are presented as a % calculated on the total number of participants.

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
Overall Survival Rate 2 months	100 Percentage of Participants NA represents not estimable.	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 3 months	100 Percentage of Participants NA represents not estimable.	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 6 months	100 Percentage of Participants NA represents not estimable.	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 12 months	87.5 Percentage of Participants Interval 38.7 to 98.1	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 15 months	87.5 Percentage of Participants Interval 38.7 to 98.1	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 21 months	87.5 Percentage of Participants Interval 38.7 to 98.1	50.0 Percentage of Participants Interval 0.6 to 91.0
Overall Survival Rate 24 months	87.5 Percentage of Participants Interval 38.7 to 98.1	50.0 Percentage of Participants Interval 0.6 to 91.0
Overall Survival Rate 27 months	72.9 Percentage of Participants Interval 27.6 to 92.5	50.0 Percentage of Participants Interval 0.6 to 91.0
Overall Survival Rate 1 month	100 Percentage of Participants NA represents not estimable.	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 9 months	100 Percentage of Participants NA represents not estimable.	100 Percentage of Participants NA represents not estimable.
Overall Survival Rate 18 months	87.5 Percentage of Participants Interval 38.7 to 98.1	100 Percentage of Participants NA represents not estimable.

POST_HOC outcome

Timeframe: 12 months, 27 months

Population: Full analysis set

On treatment deaths are collected from first patient first visit up to 30 days after study treatment discontinuation (approximately 12 months, median duration of exposure). Patients with cancer are also followed up for overall survival until the end of the trial. During overall survival (up to 27 months after the first patient first visit), additional deaths were recorded, including deaths due to the cancer disease (having occurred more than 30 days after study drug discontinuation)

Outcome measures

Outcome measures
Measure	LEE011 n=8 Participants 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo Arm n=2 Participants 600 mg daily dosing days 1-21 of a 28 day cycle
All Collected Deaths Total deaths	2 Participants	1 Participants
All Collected Deaths Deaths on treatment	0 Participants	0 Participants
All Collected Deaths Deaths post treatment survival follow up	2 Participants	1 Participants

Adverse Events

LEE011

Serious events: 3 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

All Patients

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LEE011 n=8 participants at risk 600 mg daily dosing days 1-21 of a 28 day cycle	Placebo n=2 participants at risk Placebo	All Patients n=10 participants at risk All patients
Gastrointestinal disorders Vomiting	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
General disorders Fatigue	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
General disorders Pyrexia	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Infections and infestations Meningitis bacterial	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Infections and infestations Pneumonia	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Investigations Blood creatinine increased	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Metabolism and nutrition disorders Decreased appetite	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Nervous system disorders Headache	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Renal and urinary disorders Acute kidney injury	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.
Vascular disorders Hypotension	12.5% 1/8 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	0.00% 0/2 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.	10.0% 1/10 • Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, as defined in the study protocol, for a median duration of exposure of 385 days. Any sign or symptom that occurs during the study treatment and 30 days post treatment follow up.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1-888-669-6682

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis'agreements with its investigators may vary. However Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER