LBA41 - LEAP-005: Phase II study of lenvatinib (len) plus pembrolizumab (pembro) in patients (pts) with previously treated advanced solid tumours

Background

Len (antiangiogenic multiple receptor tyrosine kinase inhibitor) + pembro (anti‒PD-1 agent) showed promising clinical outcomes across several cancers in early-phase trials and is FDA-approved for pts with previously treated advanced endometrial cancer that is not MSI-H or mismatch repair-deficient who are ineligible for curative surgery/radiation. We report the first results from the phase 2 LEAP-005 study (NCT03797326), which evaluates the efficacy and safety of len + pembro in pts with select previously treated advanced solid tumors.

Methods

This open-label, multicohort study enrolled pts aged ≥18 y with one of the following previously treated, histologically/cytologically confirmed advanced tumors: triple negative breast (TNBC), ovarian, gastric, colorectal (non-MSI-H/mismatch repair proficient), glioblastoma multiforme (GBM), or biliary tract (BTC; ampulla of Vater excluded). Pts received len 20 mg/d + pembro 200 mg Q3W for 35 cycles or until confirmed PD or unacceptable toxicity. Primary endpoints are ORR by blinded independent central review per RECIST v1.1 or RANO (GBM only), and safety.

Results

187 pts have been enrolled in LEAP-005. Median study follow-up at Apr 10, 2020 data cutoff was 8.6 (range, 1.9‒13.1) mo. Encouraging efficacy was observed across cohorts, and toxicity was manageable (Table). Table: LBA41

+, no PD as of last disease assessment; DCR, disease control rate (best confirmed response: complete/partial response; stable disease); DOR, duration of response; NR, not reached.

Conclusions

Len + pembro showed promising antitumor activity and manageable toxicity across the previously treated tumor cohorts evaluated in LEAP-005. The study is ongoing; all cohorts will expand to enroll ≤100 pts/cohort.

Clinical trial identification

NCT03797326.

Editorial acknowledgement

Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, CMPP, and Michael S. McNamara, MS, of ICON plc (North Wales, PA, USA). This assistance was cofunded by the study sponsors, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.

Legal entity responsible for the study

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

Funding

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

Disclosure

Z. Lwin: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; AstraZeneca; BMS; Roche; Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. C. Gomez-Roca: Honoraria (self): Genentech/Roche, Pierre Fabre, AstraZeneca, and BMS; Advisory/Consultancy: Erytech, BMS, Roche/Genentech, Novartis, and Eisai; Research grant/Funding (institution): BMS and Roche/Genentech; Travel/Accommodation/Expenses: Pierre Fabre, BMS, Roche/Genentech, and MSD. E. Saada-Bouzid: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS and MSD; Travel/Accommodation/Expenses: AstraZeneca. E. Yanez: Research grant: Amgen, Pfizer, Astellas, BMS, Roche, AbbVie, MSD F. Longo Muñoz: Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD, BMS, Roche, Merck, Amgen, Lilly, Sanofi, Servier, Bayer, and Ferrer Pharma. S-A. Im: Research grant/Funding (self): AstraZeneca, Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AstraZeneca, Amgen, Eisai, Novartis, Roche, Hanmi Corp, and Pfizer. E. Castanon: Travel/Accommodation/Expenses: AstraZeneca, MSD, BMS, and Roche; Advisory/Consultancy: BMS, Roche, and BeiGene. D. Graham: Research grant/Funding (institution): Pfizer; Honoraria (self): Clinigen Group and McCann Health. M. Doherty: Research grant/Funding (self): Merck and AstraZeneca; Advisory/Consultancy, Consulting fees: AstraZeneca, Merck, Eisai, Boehringer Ingelheim, Takeda, Pfizer, and Roche. J. Lopez: Advisory/Consultancy: Eisai, Novartis, and Genmab; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche, Basilea Pharmaceutica, Genmab. R. Ghori, F. Jin, K. Norwood: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P. Kubiak: Full/Part-time employment: Eisai Inc., Woodcliff Lake, NJ, USA. H.C. Chung: Research grant/Funding (self): Lilly, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, BeiGene, Incyte; Honoraria (self): Lilly/Foundation Medicine; Consultation: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, BeiGene, Amgen, Zymeworks. All other authors have declared no conflicts of interest.