In the First-in-Human, JWAA trial, the LY2780301 displayed a favourable safety profile, a high pharmacokinetic exposure and the ability to decrease pS6. LY2780301 has shown synergistic activity in combination with targeted agents or chemotherapy including gemcitabine. We propose herein to combine LY2780301 with gemcitabine and to treat different tumor types with molecular alterations. This may validate the anti-tumor activity of the LY2780301 and it will increase our knowledge regarding molecular predictors of its efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
LY2780301 will be given orally Q.D. at different dose levels. Because of a favourable safety profile, the different dose levels will be as follow : * Dose level -1: 300 mg Q.D. * Dose level -0.5: 400 mg Q.D. * Dose level 1: 400 mg Q.D. * Dose level 1.5: 500 mg Q.D. * Dose level 2 : 500 mg Q.D.
The dose level of Gemcitabine will be fixed (1000 mg/m2). Gemcitabine will be administered over a 30 minutes infusion.
Gustave Roussy
Villejuif, Val de Marne, France
Safety
Patients fulfilling the inclusion criteria will be enrolled in successive cohorts of 3 to 6 patients. If no DLT is observed during the first 4 weeks of study treatment in 3 patients, the dose of LY2780301 will be escalated to the dose level (DL) immediately above. If One DLT is observed among 3 patients, the cohort will be expanded to 6 evaluable patients. If two patients out of 3 or 2 /6 patients experience a DLT, the dose will be considered intolerable and the DL immediately below will be further explored. The recommended phase II dose (RP2D) will be the highest DL in which no more than 1/6 patients experiences a DLT. If no DLT is observed at the highest planned DL, this DL will be deemed the RP2D. Intermediate DLs could be added, if clinically relevant.
Time frame: Up to 4 weeks
Efficacy
* Solid Tumors: Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 * Non-Measurable Ovarian Cancer: Response Criteria for Patients with Ovarian Cancer Who Have Evaluable but Non-Measurable Disease * Non-Hodgkin Lymphoma: the Revised Response Criteria for Malignant Lymphoma
Time frame: Assessed every 8 weeks from inclusion until progression up to 5 months
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