Abstract 4440
Background
Pembro, a PD-1 inhibitor, has shown effective antitumor activity, durable responses, and survival benefit in pts with advanced melanoma. Len—a potent inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT—plus a PD-1 inhibitor showed superior antitumor efficacy to either agent alone in a murine tumor model. Len + pembro showed antitumor activity and was well tolerated in pts with advanced melanoma in the phase Ib/II KEYNOTE-146 trial. LEAP-003 will compare the efficacy and safety of pembro ± len in advanced melanoma (NCT03820986).
Trial design
Eligibility criteria include ≥18 y, histologically/cytologically confirmed unresectable untreated stage III-IV melanoma, documented BRAFV600 status, ECOG performance status 0/1, toxicity resolution from most recent therapy, and provision of baseline tumor sample. Prior first-line standard of care targeted therapy allowed only if pt has BRAFV600-mutant disease. Prior targeted therapy or immunotherapy (as adjuvant/neoadjuvant) allowed if relapse did not occur during treatment or ≤ 6 mo after discontinuation. Pts will be randomized 1:1 to pembro 200 mg every 3 weeks (Q3W) IV plus len 20 mg or placebo QD PO. Randomization will be stratified by BRAF status (mutant/WT), prior adjuvant therapy (PD-1 inhibitor, yes/no), geographic region (China, yes/no). Pembro will continue for up to ∼2 y; len or placebo may continue beyond 2 y in cases of clinical benefit, until progression, unacceptable toxicity, or investigator/pt decision. Response will be assessed per RECIST v1.1 Q9W until wk 54, Q12W until wk 102, and Q24W thereafter. Pts with a CR can discontinue treatment after ≥24 wk of pembro and ≥2 pembro doses after initial CR. Eligible pts can continue treatment beyond initial RECIST-defined PD. AEs will be assessed for ≤90 d and graded per NCI CTCAE v4.0. Survival follow-up will be Q12W. Primary end points are PFS by blinded independent central review (BICR) per modified RECIST v1.1 (max target lesions: 10; 5 per organ) and OS. Secondary end points are ORR and DOR (by BICR per modified RECIST v1.1), safety, and pt-reported health outcomes. Exploratory biomarker and PK analyses of len plus pembro are planned.
Clinical trial identification
NCT03820986; release date: January 29, 2019.
Editorial acknowledgement
Doyel Mitra, PhD, CMPP, and Harleigh E. Willmott, PhD, CMPP, of the ApotheCom pembrolizumab team (Yardley, PA, USA).
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
A.M.M. Eggermont: Honoraria (self): Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech, IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Advisory / Consultancy: Actelion, BMS, GSK, Ellipses, Incyte, IO Biotech, IsaPhamaceuticals, MSD, Novartis, Pfizer, Sanofi, Sellas, SkylineDx; Speaker Bureau / Expert testimony: MSD. M.S. Carlino: Honoraria (self): MSD, BMS; Advisory / Consultancy: MSD, BMS, Novartis, Roche, Merck, Pierre Fabre. A. Hauschild: Honoraria (self): Amgen, BMS, MSD/Merck, Novartis, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Honoraria (institution), Support for clinical trials: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, Sanofi-Genzyme; Advisory / Consultancy: Amgen, BMS, MerckSerono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, OncoSec, Sanofi-Genzyme, Sun Pharma. P.A. Ascierto: Advisory / Consultancy: BMS, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, Newlink Genetics, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC; Research grant / Funding (self): BMS, Roche-Genentech, Array; Travel / Accommodation / Expenses: MSD. A. Arance: Advisory / Consultancy: BMS, MSD, Roche, Novartis, Merck; Travel / Accommodation / Expenses: BMS, MSD, Roche, Novartis, Merck. A. Daud: Advisory / Consultancy: Merck, Pfizer, BMS, Genentech, Incyte, Novartis; Shareholder / Stockholder / Stock options: SQZ; Research grant / Funding (self): BMS, Pfizer, Incyte, Checkmate, Merck. S.J. O’Day: Advisory / Consultancy: Biothera, BMS, Merck, RadImmune, ImaginAB; Speaker Bureau / Expert testimony: BMS; Travel / Accommodation / Expenses: Biothera, BMS, Merck, RadImmune, ImaginAB; Research grant / Funding (institution): Amgen, Biothera, Exicure, Genocea, Incyte, Oncothereapeutics, Ultimovacs, Viralytics. M.H. Taylor: Honoraria (self): BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Advisory / Consultancy: BMS, Eisai Inc, Array Biopharma, Arqule, Blueprint Medicines, Bayer, Loxo Oncology, Novartis; Speaker Bureau / Expert testimony: BMS, Eisai Inc. A. Smith: Full / Part-time employment: Eisai. A. Rodgers: Full / Part-time employment: Merck & Co., Inc. B. Homet Moreno: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.J. Diede: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. H. Kluger: Research grant / Funding (institution): Merck, BMS, Apexigen; Honoraria (self): Regeneron, Alexion, Prometheus, Corvus, Nektar, Biodesix, Roche/Genentech, Pfizer, Iovance, Immunocore, Celldex, Array BioPharma.
Resources from the same session
2316 - A 3D co-culture platform of breast cancer and patient derived immune cells to analyse the response to chemotherapy and immunotherapies
Presenter: Diana Saraiva
Session: Poster Display session 3
Resources:
Abstract
4290 - Characterization of the mechanism of action and efficacy of MEN1611 (PA799), a novel PI3K inhibitor, in breast cancer preclinical models.
Presenter: Alessio Fiascarelli
Session: Poster Display session 3
Resources:
Abstract
2167 - Neat-1: culprit lnRNA tying PIG-C, MSLN, CD80 in TNBC
Presenter: Nada Hussein
Session: Poster Display session 3
Resources:
Abstract
1829 - A novel RAF/MEK inhibitor CH5126766 in phase 1 clinical trial has an effectiveness in the combination with eribulin for the treatment of triple negative breast cancer
Presenter: Hisako Ono
Session: Poster Display session 3
Resources:
Abstract
4357 - Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer
Presenter: Eva Galan-Moya
Session: Poster Display session 3
Resources:
Abstract
5163 - Preclinical Evaluation targeting both IGF1R and IR in Triple Negative Breast Cancer
Presenter: Alex Eustace
Session: Poster Display session 3
Resources:
Abstract
832 - Monospecific antibody targeting of CDH11 inhibits epithelial-to-mesenchymal transition and represses cancer stem cell-like phenotype by up-regulating miR-335 in metastatic breast cancer, in vitro and in vivo.
Presenter: Jia-Hong Chen
Session: Poster Display session 3
Resources:
Abstract
3781 - Pharmacological screening with Chk1 inhibitors identify synergistic agents to overcome resistance to platinums in basal breast and ovarian cancer
Presenter: Ana Lucia Sanabria
Session: Poster Display session 3
Resources:
Abstract
3275 - Comparison of 11 circulating miRNAs and CA125 kinetics in ovarian cancer during first line treatment: data from the randomized CHIVA trial (a GINECO-GCIG study)
Presenter: Patrick Robelin
Session: Poster Display session 3
Resources:
Abstract
3391 - Inhibiting Ehmt2 and Ezh2 histone methyltransferases alters the immune microenvironment in a Trp53-/- murine ovarian cancer model
Presenter: Pavlina Spiliopoulou
Session: Poster Display session 3
Resources:
Abstract