A Randomized, Blinded, Placebo-controlled, Phase II Trial of LEE011 in Patients With Relapsed, Refractory, Incurable Teratoma With Recent Progression

This was a multi-center, randomized, double blind (investigator and subject), placebo controlled Phase II study to determine the efficacy and safety of treatment with ribociclib versus placebo in subjects with progressive relapsed, refractory incurable teratoma. Eligible subjects were randomized in a 2:1 ratio to ribociclib or placebo.

After discontinuation of study treatment, patients were followed up for safety, disease progression and overall survival.

Safety follow-up: After discontinuation of study treatment, all subjects were followed for safety for 30 days except in the case of death, loss to follow up, withdrawal of consent, or discontinuation of study treatment to enroll in the ribociclib rollover clinical trial (CLEE011X2X01B).

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.

Survival follow-up: All subjects were followed for survival via a phone call (or during a clinic visit) every 12 weeks and up to one additional time per quarter if a survival update was required to meet safety or regulatory needs. The safety follow-up was carried out until any of the following occurred (whichever occurred first): death, withdrawal of consent, loss to follow-up, at least 18 months had elapsed from when the last subject had started treatment, or when 80% of subjects had died or were lost to follow-up, or early study termination.

Eligibility Criteria:
Key Inclusion Criteria:

* Diagnosis of teratoma for which no additional standard surgical or medical therapy exists
* Patients must have completed at least 1 prior line of chemotherapy for germ cell tumor (except patients who present with primary pure teratoma who need not have received any previous chemotherapy)
* Radiographic progression, defined by RECIST v.1.1, after the last cancer treatment and within 12 weeks prior to enrollment, compared with scans within 1 year of enrollment.
* Availability of an archival or newly obtained tumor sample (collected at diagnosis or progression) with accompanying pathology report
* Meaurable or evaluable extra-cranial disease as defined by RECIST v 1.1

Key Exclusion Criteria:

* Malignant germ cell tumors with mixed histology such as embryonal carcinoma, choriocarcinoma, yolk sac tumor or seminoma. Note - this refers to the histology at the time of enrollment, not the histolgy at the time of initial presentation.
* Pathologic evidence of malignant transformation
* CNS disease unless radiation therapy and/or surgery has been completed and serial evaluation demonstrates stable disease
* Prior treatment with any CDK4/6 inhibitor therapy
* Systemic antineoplastic therapy or any experimental therapy within 3 weeks before the first dose of study drug (6 weeks for prior nitrosoureas, bevacizumab, or mitomycin C)
* Major surgery ≤ 2 weeks or radiotherapy ≤ 4 weeks prior to planned start of study drug or patient has not recovered from major side effects.
* Requirement for treatment with any of the prohibited medications including strong CYP3A inhibitors, strong CYP3A inducers, CYP3A substrates with a narrow therapeutic index, and medications with strong risk of QT prolongation