Abstract 710P
Background
LEN + everolimus is approved for advanced RCC after prior VEGF-targeted therapy. PEMBRO + axitinib is approved as first-line therapy for advanced RCC. We report phase 2 results of the RCC cohort of a phase 1b/2 trial (Study 111/KEYNOTE-146) of LEN + PEMBRO in patients (pts) whose disease progressed after ICI therapy.
Methods
This multicenter, open-label study enrolled pts with mccRCC who previously had disease progression per RECIST v1.1 (confirmed ≥ 4 weeks later) during or following ICI therapy, and measurable disease per irRECIST. Pts received LEN 20 mg orally once daily + PEMBRO 200 mg IV every 3 weeks until disease progression or toxicity. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at week 24 by irRECIST.
Results
For the 104 pts enrolled, median duration of follow-up for OS was 12.3 months, 65% of pts had prior anti-PD-1/PD-L1 and anti-VEGF therapy in combination or sequentially, and 37% of pts had prior nivolumab + ipilimumab. At week 24, 53/104 pts achieved a confirmed partial response for an ORR of 51% by investigator assessment (Table). Median duration of response (DOR) was 12.2 months and median progression-free survival (PFS) was 11.7 months by irRECIST. The most common treatment-related adverse events (TRAEs) were fatigue (53%), diarrhea (46%), proteinuria (39%), dysphonia (35%), hypertension (34%), nausea (32%), and stomatitis (32%). There were 2 grade 5 TRAEs (upper gastrointestinal hemorrhage; sudden death). TRAEs led to discontinuation of study drug in 15% of pts. Data by independent imaging review and additional subgroup analyses will be available upon presentation. Table: 710P
| Efficacy by investigator assessment | irRECIST N=104 | RECIST v1.1 N=104 |
| ORR, n/N (%) [95% CI] | 57/104 (54.8) [44.7–64.6] | 54/104 (51.9) [41.9–61.8] |
| Prior anti-PD-1/PD-L1 and anti-VEGF | 40/68 (58.8) [46.2–70.6] | – |
| Prior nivolumab + ipilimumab | 18/38 (47.4) [31–64.2] | – |
| MSKCC risk group | ||
| Favorable | 23/37 (62.2) [44.8–77.5] | – |
| Intermediate | 25/44 (56.8) [41–71.7] | – |
| Poor | 9/23 (39.1) [19.7–61.5] | – |
| PD-L1 status | ||
| Positive | 22/44 (50) [34.6–65.4] | – |
| Negative | 27/43 (62.8) [46.7–77] | – |
| ORR (week 24), n (%) [95% CI] | 53 (51) [41–60.9] | – |
| DOR a (95% CI) | 12.2 (8.5–18.2) | 12.2 (8.9–18.2) |
| Time to response a (range) | 1.6 (1.2–13.7) | 1.6 (1.2–13.7) |
| PFS a (95% CI) | 11.7 (9.4–17.7) | 11.3 (7.6–17.7) |
| OS a | Not reached |
aMedian, months
Conclusions
LEN + PEMBRO demonstrated promising antitumor activity in mccRCC after ICI therapy. No new safety signals were detected.
Clinical trial identification
NCT02501096.
Editorial acknowledgement
Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Eisai Inc., Woodcliff Lake, NJ, USA, and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
C-H. Lee: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution), Travel/Accommodation/Expenses: Calithera; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eisai; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Amgen; Advisory/Consultancy: Merck; Research grant/Funding (institution): Lilly. A.Y. Shah: Honoraria (self): Eisai Inc.; Honoraria (self): Oncology Information Group; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Eisai Inc.; Research grant/Funding (institution): Bristol-Myers Squibb. J.J. Hsieh: Advisory/Consultancy, Research grant/Funding (institution): Eisai Inc.; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Calithera; Research grant/Funding (institution): SillaJen; Research grant/Funding (institution): BostonGene; Research grant/Funding (institution): TScan. A. Rao: Advisory/Consultancy: QED Therapeutics; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Pfizer; Honoraria (self): Eli Lilly; Honoraria (self): Clovis Oncology; Honoraria (self): Sanofi-Genzyme. M.A. Bilen: Advisory/Consultancy, Research grant/Funding (institution): Xencor; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Genentech/Roche; Advisory/Consultancy, Research grant/Funding (institution): Nektar; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Tricon Pharmaceuticals; Research grant/Funding (institution): Peleton Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Eisai; Advisory/Consultancy: Janssen; Advisory/Consultancy: Genomic Heath; Advisory/Consultancy: Sanofi. R. Girones Sarrio: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Pfizer; Advisory/Consultancy: EUSA; Advisory/Consultancy: Roche. J. Wu: Full/Part-time employment: Eisai Inc. E. Schmidt: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck & Co., Inc.. P. Kubiak: Full/Part-time employment: Eisai Inc.; Shareholder/Stockholder/Stock options: Mallinckrodt; Shareholder/Stockholder/Stock options: Ziopharm; Shareholder/Stockholder/Stock options: Immunogen; Shareholder/Stockholder/Stock options: Apyx; Shareholder/Stockholder/Stock options: Seres; Shareholder/Stockholder/Stock options: Sesen. C.E. Okpara: Full/Part-time employment: Eisai Ltd. A.D. Smith: Full/Part-time employment: Eisai Ltd. 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; Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy: Novartis. All other authors have declared no conflicts of interest.