1600P - Phase II trial of pembrolizumab and lenvatinib in advanced neuroendocrine prostate cancer (NEPC)

Background

Lenvatinib and pembrolizumab has demonstrated preclinical synergy in small cell/neuroendocrine cancer cell lines and clinical tolerability is noted A multicenter phase II trial of the combination in NEPC was conducted.

Methods

Eligible patients had histologically proven prostate cancer with radiologic evidence of metastases and either: A) Small-cell or NEPC B) positive staining for chromogranin and synaptophysin C) visceral metastases and a PSA< 5 ng/dL.D) Serum chromogranin A level = 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) = 2× ULN. E) RB1 deletions or mutations F) Trans-differentiated or poorly-differentiated carcinoma. 2 prior chemotherapy regimens were allowed. Performance status of 0-1 and normal marrow, renal and liver function were required. Primary endpoint was 6- month radiologic progression-free survival (rPFS). Stud therapy was Lenvatinib 20 mg orally daily and intravenous pembrolizumab 200 mg every 21 days. Sample size was 27 for first stage and if 3 patients were progression free at 6 months then total accrual was 40 evaluable patients.

Results

33 patients enrolled; median age was 71 years (range- 37-83 years), 3 (10%) black patients and 3 (10%) of Hispanic ethnicity. 13/22 (59%) had Gleason ≥ 8, 31 (94%) patients had small cell/NEPC, 1 patient qualified based on serum NE markers, 1 had transdifferentiated histology. RB loss was noted in 3 of 11 patients. 12/31 (39%) patients had liver metastases and 30 (91%) had measurable disease. 31 (94%) patients received prior chemotherapy and 23 (70%) received prior platinum. No treatment related deaths were noted. Grade 4 toxicities of lipase elevation and urinary obstruction were noted in 1 patient each. Grade 3 toxicities of hypertension, diarrhea, fatigue and proteinuria occurred in 6, 2, 5 and 3 patients respectively. 21 pts are response evaluable to date. 3 (14%) had partial response. 7 (33%) had stable disease. Five patients remain progression free at 6 months. The primary endpoint of first stage was met. Accrual to second stage is ongoing. PFS and OS will be reported.

Conclusions

The combination of lenvatinib and pembrolizumab demonstrated tolerability and promising efficacy in a pretreated patient population with NEPC.

Clinical trial identification

NCT04848337.

Editorial acknowledgement

Legal entity responsible for the study

Hoosier Cancer Research Network.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA provided drug and financial support.

Disclosure

U.N. Vaishampayan: Financial Interests, Personal, Advisory Board, consultant: BMS; Financial Interests, Personal, Advisory Board: Bayer, Gilead, Pfizer, Merck, Exelixis, Novartis; Financial Interests, Institutional, Research Grant, Investigator initiated trial supported by Merck: Merck; Non-Financial Interests, Member of Board of Directors: Michigan Society of Hematology/Oncology. D. Kilari: Financial Interests, Personal, Invited Speaker: Janssen, Pfizer, Aveo oncology, Seagen, MJH - life sciences, Binayatra foundation; Financial Interests, Personal, Advisory Board: Exelixis, Eisai; Financial Interests, Institutional, Coordinating PI: Exelixis, Genentech. T.B. Dorff: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Sanofi, Bayer. A.O. Sokolova: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lantheus; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. Z. Reichert: Financial Interests, Personal, Advisory Board: Huff Powell Bailey, AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Celgene. J. Alumkal: Financial Interests, Personal, Advisory Board: Fibrogen; Financial Interests, Institutional, Funding: Pfizer, Beactica, Zenith; Financial Interests, Personal and Institutional, Advisory Role, Research award: Astellas; Financial Interests, Personal, Advisory Role: Bristol-Myers-Squibb. All other authors have declared no conflicts of interest.