Greater antitumor activity was seen with LEN/PEM vs either agent alone in colorectal and lung cancer models. We report initial results of an ongoing, open-label, multicenter, phase 1b trial of LEN/PEM in patients (pts) with selected solid tumors (non-small cell lung cancer [NSCLC], renal cell carcinoma [RCC], endometrial cancer, urothelial cancer, head and neck squamous cell carcinoma, and melanoma).
The study enrolled pts aged ≥18 y with histologically and/or cytologically confirmed metastatic selected solid tumors that progressed after approved therapies or for which no standard effective therapies were available. Pts received 200 mg PEM IV once every 3 wks, and 1 of 2 LEN dose levels (DL) PO (DL1: 24 mg/d; DL2: 20 mg/d). Primary endpoint was maximum tolerated dose (MTD); key secondary endpoints were safety, tolerability, and objective response rate (ORR) per irRECIST. Tumor assessments were performed every 6 wks until wk 24, then every 9 wks.
As of 10 Apr 2016, enrollment was completed with 13 pts (NSCLC: n = 2; RCC: n = 8, endometrial cancer: n = 2; melanoma: n = 1) (DL1: n = 3; DL2: n = 10). At DL1, there were 2 dose-limiting toxicities (DLTs): 1 grade 3 arthralgia and 1 grade 3 fatigue; no DLTs have been reported in DL2. DL2 was determined to be the MTD. All pts had at least 1 treatment-emergent adverse event (TEAE). TEAEs requiring dose modifications included increased liver function tests, fatigue, hypertension, arthralgia, decreased appetite, dehydration, diarrhea, hyponatremia, noncardiac chest pain, palmar-plantar erythrodysesthesia, proteinuria, maculopapular rash, and rhabdomyolysis. No pts have discontinued treatment due to TEAEs. At data cutoff, all pts had postbaseline tumor assessments (Table).
LEN had an MTD of 20mg/d in the LEN/PEM regimen, which showed promising activity with all partial responses (PR). Toxicities were manageable with dose modification of LEN, and no new safety signals were identified.
|n (%)||LEN 24 mg/d (n = 3)||LEN 20 mg/d (n = 10)||Total (n = 13)|
|ORR||3 (100)||4 (40)||7 (54)|
|Best Overall Response|
|PR||3 (100)||4 (40 )||7 (54)a|
|Stable disease||0||6 (60)||6 (46)b|
a4 RCC, 1 NSCLC, 1 endometrial, 1 melanoma b4 RCC, 1 NSCLC, I endometrial All pts received at least 2 post-treatment tumor assessments
Clinical trial identification
Legal entity responsible for the study
Eisai Inc., and Merck & Co., Inc
Eisai Inc and Merck & Co., Inc
M. Taylor: Honoraria: Eisai Advisory Board: Eisai, ONYX. C.E. Dutcus, T. Bagulho: Employee of Eisai Inc.,. C.E. Dutcus, D. Li, R. Shumaker: Employee of Eisai Inc.,. E. Schmidt: Employee of Merck Research Labs (with stock). D. Rasco: Research Funding: Aeglea, Asana, Bayer, Celgene, FivePrime, Pharmacyclics, Eisai, Takeda, Rexahn, Santa Maria Travel Expenses- Takeda.