Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Discussion 2 – Immunotherapy of cancer

4181 - Phase 2 study of lenvatinib plus pembrolizumab for disease progression after PD-1/PD-L1 immune checkpoint inhibitor in metastatic clear cell renal cell carcinoma (mccRCC): results of an interim analysis

Date

30 Sep 2019

Session

Poster Discussion 2 – Immunotherapy of cancer

Presenters

Chung-Han Lee

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

C. Lee1, A.Y. Shah2, V. Makker3, M.H. Taylor4, D. Shaffer5, J.J. Hsieh6, A.L. Cohn7, C. DiSimone8, A. Pinto Marin9, D.W. Rasco10, S.G. Ribe11, D.A. Richards12, D.E. Stepan13, C.E. Dutcus14, J. Wu15, E.V. Schmidt16, R.F. Perini17, R.J. Motzer18

Author affiliations

  • 1 Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2 Genitourinary Medical Oncology, MD Anderson Cancer Center, University of Texas, 77030 - Houston/US
  • 3 Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York City/US
  • 4 Division Of Hematology & Medical Oncology, Oregon Health and Science University, 97210 - Portland/US
  • 5 Medical Oncology, New York Oncology Hematology, 12208 - Albany/US
  • 6 Department Of Medicine, Oncology Division, Washington University School of Medicine in St. Louis, 63110 - St. Louis/US
  • 7 Medical Oncology, Rocky Mountain Cancer Center, 80208 - Denver/US
  • 8 Medical Oncology/hematolgy, Arizona Oncology Associates, 85711 - Tucson/US
  • 9 Medical Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 10 Clinical Research, South Texas Accelerated Research Therapeutics, TX 78229 - San Antonio/US
  • 11 Medical Oncology, Sorlandet Hospital, 4615 - Kristiansand/NO
  • 12 Medical Oncology, Texas Oncology, US Oncology Research, 75702 - Tyler/US
  • 13 Clinical Research, Formerly of Eisai Inc, 07677 - Woodcliff Lake/US
  • 14 Clinical Research, Eisai Inc., NJ 07677 - Woodcliff Lake/US
  • 15 Biostatistics, Oncology Business Group, Eisai Inc., 07677 - Woodcliff Lake/US
  • 16 Early Oncology, Clinical Development, Merck & Co. Inc., 07033 - Kenilworth/US
  • 17 Clinical Research, Merck & Co. Inc., 07033 - Kenilworth/US
  • 18 Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US

Resources

Login to access the resources on OncologyPRO.

If you do not have an ESMO account, please create one for free.

Abstract 4181

Background

Lenvatinib (LEN) is a multikinase VEGFR inhibitor approved for use in combination with everolimus to treat advanced RCC after prior VEGF-targeted therapy. Pembrolizumab (PEMBRO) is an anti-PD-1 antibody. Here, we report results of an interim analysis of the RCC cohort of a phase II trial of LEN + PEMBRO, specifically in patients (pts) who progressed with prior immune checkpoint inhibitor (ICI) therapy.

Methods

This is a per-protocol interim analysis of a multicenter, open-label study for pts with mccRCC, ≥1 prior therapy, RECIST disease progression on or following an ICI regimen (confirmed ≥ 4 weeks later), measurable disease, and Eastern Cooperative Oncology Group performance status ≤ 1. Pts received LEN 20 mg/d PO plus PEMBRO 200 mg intravenously Q3W until disease progression or toxicity occurred. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks.

Results

At data cutoff (March 29, 2019), the first 33 pts enrolled were followed for ≥12 weeks for response evaluation, and 24 (73%) pts were still on study treatment. The objective response rate was 52%, the disease control rate was 94%, and most pts had tumor shrinkage. Median follow-up time for progression-free survival was 4.2 months. Pt characteristics and efficacy outcomes are summarized in the table. The most common treatment-related adverse events were fatigue (49%), dysphonia (36%), diarrhea (33%), stomatitis (30%), hypertension (24%), dry mouth, nausea, proteinuria, and hand-foot syndrome (21% each). Three (9%) pts discontinued treatment due to adverse events.Table:

1187PD Summary of patient characteristics and efficacy outcomes

Patient Characteristics, n (%)LEN + PEMBRO (n = 33)
ECOG performance status
018 (54.5)
115 (45.5)
Prior anticancer regimens
1 prior regimen14 (42%)
>1 prior regimen19 (58%)
Prior VEGF-targeted therapy26 (78.8%)
Prior ICI therapy33 (100%)
PD-1/PD-L1 monotherapy14 (42.4%)
with VEGF agents9 (27.7%)
nivolumab + ipilimumab7 (21.2%)
with other agents2 (6.1%)
PD-L1 positive12 (36.4)*
Investigator assessment of efficacy outcomes by irRECISTLEN + PEMBRO (n = 33)
ORR, n (%) 95% CI17 (51.5) 33.5–69.2
Median PFS (95% CI), months PFS rate, % (95% CI) at: 3 months 6 months 9 monthsNR (5.6–NR) 93.4 (76.1–98.3) 73.8 (45.7–88.9) 64.6 (34.5–83.5)
Median DOR, (95% CI) monthsNR (4.2–NR)
Median follow-up time for DOR, months6.0 (1.4–7.0)
Response duration > = 6 months, n (%)**80.8 (42.3–94.9)
*

30.3% were negative and 33.3% were not available

**

Response duration is based on Kaplan-Meier estimation with 95% CI based on the Greenwood formula using log-log transformation DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; irRECIST, immune-related Response Evaluation Criteria In Solid Tumors; NR, not reached; ORR, objective response rate; PD-L1, programmed death-ligand-1; PFS, progression-free survival; VEGF, vascular endothelial growth factor.

Conclusions

For the subset of mccRCC pts with disease progression during or following ICI therapy, LEN + PEMBRO demonstrated promising antitumor activity. No new safety signals were detected. The study will continue to full cohort expansion.

Clinical trial identification

NCT02501096; Release date: July 17, 2015.

Editorial acknowledgement

Tarah M. Connolly, PhD of Oxford PharmaGenesis, Newtown, PA, funded by Eisai Inc.

Legal entity responsible for the study

Eisai Inc.

Funding

Eisai Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

C. Lee: Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Calithera; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Amgen. A.Y. Shah: Honoraria (self), Non-remunerated activity/ies, research: Eisai Inc.; Honoraria (self): Oncology Information Group; Non-remunerated activity/ies, research: EMD Serono; Non-remunerated activity/ies, research: Bristol-Myers Squibb. V. Makker: Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Eisai; Honoraria (self), Non-remunerated activity/ies: Merck; Non-remunerated activity/ies: Lilly; Honoraria (self), Non-remunerated activity/ies: Karyopharm; Non-remunerated activity/ies: Takeda; Non-remunerated activity/ies: Genentech. M.H. Taylor: Research grant / Funding (institution): BioAlta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Array Biopharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: LOXO; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Blueprint; Honoraria (self), Advisory / Consultancy: Arquele; Honoraria (self), Advisory / Consultancy: Novartis. J.J. Hsieh: Honoraria (self): Eisai Inc. A. Pinto Marin: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony: EUSA Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis; Honoraria (self): Aveo. D.W. Rasco: Research grant / Funding (self): Eisai Inc.; Research grant / Funding (self): Merck. D.E. Stepan: Full / Part-time employment: Formerly of Eisai Inc. C.E. Dutcus: Leadership role, Full / Part-time employment: Eisai Inc. J. Wu: Full / Part-time employment: Eisai Inc. E.V. Schmidt: Full / Part-time employment: Merck & Co Inc. R.F. Perini: Full / Part-time employment: Merck & Co Inc. R.J. Motzer: Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Eisai; Advisory / Consultancy, Research grant / Funding (self): Exelixis; Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Novartis; Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy: Merck; Advisory / Consultancy: Incyte. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.