Table-2:

Summary of Early Clinical Studies:

Tx	Trial	Population	Results	Ref
Everolimus	Dose escalation Phase I	Patients with refractory advanced solid tumors including PDAC.	0% ORR; increased pAkt and mTOR activation.	31
Everolimus	Phase II	GR metastatic PDAC	0% ORR and 7% SD.	32
Everolimus	Phase II	PIK3CA amplified/mutated and/or PTEN loss in advanced refractory solid tumors.	0% ORR/SD.	33
Everolimus + erlotinib	Phase II	Advanced PDAC	0% ORR/SD.	34
Capecitabine + cetuximab + everolimus	Phase I/II	Advanced PDAC	Everolimus limited to 5 mg daily; 6.5% PR, 16% SD; mOS 5 months.	35
Capecitabine + everolimus	Followup phase II	Advanced PDAC	6% ORR; 32% SD; mOS 8.9 months; 45% hyperglycemia.	37
Everolimus + gemcitabine + cisplatin	Phase I, (3+3)	Advanced solid tumors	Cohort I: 1 PDAC pt had CR, Cohort II: 0%ORR, Cohort III: 0% ORR. Overall 18.5% ORR and 66.6% DCR.	38
Everolimus + gemcitabine	Phase I	Advanced PDAC	MTD: gemcitabine 400 mg/m2/week and everolimus 5mg daily. 78% clinical benefit rate, 65% SD, and 13% PR.	39
Everolimus + trametinib	Phase Ib	Advanced refractory solid tumors	33% serious adverse event; PDAC pt 5%PR, 29%SD. Phase II dose not identified.	41
Everolimus + ribociclib	Phase I (3+3)	Advanced PDAC refractory to 5-fluorouracil (5-FU) and gemcitabine-based chemotherapy	Ongoing – endpoints: PFS, OS, adverse events, best response.	42

CR: complete response; DCR: disease control rate; GR: gemcitabine resistant; MTD: maximum tolerated dose; OS: overall survival; ORR: overall response rate; PDAC: pancreatic ductal adenocarcinoma; PFS: progression free survival; PR: partial response; SD: stable disease.