All times are listed in CEST (Central European Summer Time)
- Andre P. Fay (Porto Alegre, Brazil)
- Laurence Albiges (Villejuif, Cedex, France)
LBA68 - Bempegaldesleukin (BEMPEG) plus nivolumab (NIVO) compared to the investigator’s choice of sunitinib or cabozantinib in previously untreated advanced renal cell carcinoma (RCC): Results from a phase III randomized study (PIVOT-09)
- Nizar Tannir (Houston, United States of America)
Abstract
Background
Checkpoint inhibitor (CPI) combinations improve clinical outcomes for patients (pts) with advanced RCC. BEMPEG is a pegylated IL-2 prodrug, designed with the intent to preferentially bind to IL-2Rβγ. PIVOT-09 is a Phase III, randomized trial of BEMPEG + NIVO vs VEGF-targeted tyrosine kinase inhibitor (TKI) of investigator’s choice for 1L RCC (NCT03729245).
Methods
Adult pts with measurable and untreated advanced/metastatic clear-cell RCC were randomized 1:1 (stratified by IMDC risk score and TKI choice) to receive BEMPEG IV 0.006 mg/kg + NIVO IV 360 mg q3w vs sunitinib 50 mg PO qd for 4 weeks followed by 2 weeks off, or cabozantinib 60 mg PO qd. Primary endpoints were objective response rate (ORR) by blinded independent central review (BICR) and overall survival (OS) in pts with IMDC intermediate (I) or poor (P) risk, and in IMDC all-risk disease. The overall study α is 0.05 (2-sided), which is split with 0.001 for ORR and 0.049 for OS.
Results
623 pts (IMDC I/P n=514; IMDC favorable n=109) were randomized and 616 pts (IMDC I/P n=509; IMDC favorable n=107) received ≥1 dose of treatment (sunitinib n=221; cabozantinib n=85). Efficacy results for the IMDC I/P groups are reported. At a median duration of follow-up of 15.5 months, ORR was 23.0% for BEMPEG + NIVO vs 30.6% for the TKI arm. OS in IMDC I/P with p-value of 0.19 did not pass the pre-specified alpha of 0.01 at the interim analysis. mOS was 29.0 months for BEMPEG + NIVO and not reached for the TKI arm (HR=0.82, 99% CI: 0.56-1.21). In IMDC all-risk group, the most common treatment-related adverse events (TRAEs, >20%) of any grade in BEMPEG + NIVO arm were pyrexia (32.6%), pruritus (31.3%), nausea (24.2%), eosinophilia (23.9%), hypothyroidism (22.9%), rash (22.9%), and arthralgia (20.0%). Grade ≥3 TRAEs occurred in 83 pts (26.8%) and 24 pts (7.7%) discontinued due to TRAEs for BEMPEG or NIVO. Grade 5 TRAEs occurred in 3/310 pts (1.0%).
Conclusions
In pts with treatment-naïve advanced/metastatic clear-cell RCC, BEMPEG + NIVO did not improve outcomes vs investigator’s choice of TKI. The combination’s safety profile was consistent with previous reported findings.
Clinical trial identification
NCT03729245; Trial protocol: 17-214-09 / CA045-002 (October 19, 2021).
Editorial acknowledgement
Medical writing and editorial assistance was provided by BOLDSCIENCE Inc. funded by Nektar Therapeutics.
Legal entity responsible for the study
Nektar Therapeutics, San Francisco, CA and Bristol Myers Squibb, Princeton, NJ.
Funding
This study is sponsored by Nektar Therapeutics, San Francisco, CA, and Bristol Myers Squibb, Princeton, NJ.
Disclosure
All authors have declared no conflicts of interest.
LBA73 - Study EV-103 Cohort K: Antitumor activity of enfortumab vedotin (EV) monotherapy or in combination with pembrolizumab (P) in previously untreated cisplatin-ineligible patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC)
- Jonathan E. Rosenberg (New York, United States of America)
Abstract
Background
There is a critical need for effective and tolerable 1L treatment options in la/mUC. Both EV and P have independently shown an OS benefit in previously treated la/mUC. EV preclinical studies have shown hallmarks of immune cell death potentially augmented by PD-1/PD-L1 inhibitors. Results from a previous cohort formed the rationale for this randomized Cohort K.
Methods
Previously untreated cisplatin-ineligible pts with la/mUC were randomized 1:1 to EV (1.25 mg/kg) as monotherapy on Days 1 and 8 or in combination with P (200 mg) on Day 1 of 3-week cycles (EV-103, NCT03288545). The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by BICR. Secondary endpoints included duration of response (DOR) and safety (treatment-related adverse events, TRAEs). There were no formal statistical comparisons between treatment arms.
Results
149 pts were treated: EV+P n=76; EV n=73. Confirmed ORR (95%CI) for EV+P, 64.5% (52.7, 75.1), median DOR was not reached. Confirmed ORR (95%CI) for EV, 45.2% (33.5, 57.3) and median DOR (95%CI) 13.2 mos (6.1, 16.0). TRAEs of special interest included skin reactions (EV+P, n=51 [67.1%]; EV, n=33 [45.2%]), peripheral neuropathy (EV+P, n=46 [60.5%]; EV, n=40 [54.8%]), ocular disorders (eg, dry eye and blurred vision; EV+P, n=20 [26.3%]; EV, n=21 [28.8%]), and hyperglycemia (EV+P, n=11 [14.5%]; EV, n=8 [11.0%]). The majority of treatment-related AESIs were Grade ≤2. Data cutoff: June 10, 2022; +Pts remain on treatment.
EV+P EV mono (N=76) (N=73) 64.5 (52.7, 75.1) 45.2 (33.5, 57.3) Complete Response 10.5 4.1 Partial Response 53.9 41.1 Stable Disease 22.4 34.2 Progressive Disease 7.9 9.6 Not Evaluable 3.9 6.8 No Assessment 1.3 4.1 2.1 (1.1, 6.6) 2.1 (1.9, 15.4) 9.0 (0.6, 26.1+) 5.5 (0.5, 26.9+) 14.8 (12.9, 17.3) 15.0 (12.7, 17.4)
Conclusions
EV+P showed high ORR with rapid responses and median DOR not reached in a 1L cisplatin-ineligible population. The safety profile was tolerable and generally consistent with the known profile for EV+P. EV monotherapy was consistent with prior experience. These data support ongoing investigations of 1L EV+P in patients with la/mUC who have a high unmet need.
Clinical trial identification
NCT03288545.
Editorial acknowledgement
Holly Tomlin, MPH, Ray Liao, and Nancy Chang (employees and stockholders, Seagen Inc.) provided writing and editorial assistance.
Legal entity responsible for the study
Seagen Inc., Astellas Pharma, and Merck & Co., Inc.
Funding
Seagen Inc., Astellas Pharma, Merck & Co., Inc.
Disclosure
J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Seagen, Astellas, AstraZeneca, EMD-Serono, Mirati, Tyra Biosciences, Alligator Biosciences, Gilead, QED Therapeutics, Boehringer Ingelheim, Genentech, Pfizer, Infinity Pharmaceuticals, BMS, Janssen, Merck, Lilly Oncology, NCCN; Financial Interests, Personal, Invited Speaker: EMD-Serono; Financial Interests, Personal, Invited Speaker, Medical education: Research to Practice, Physicians Education Resource, MJH Associates; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options; Financial Interests, Personal, Royalties: Wolters Kluyer/Uptodate; Financial Interests, Institutional, Invited Speaker, Coordinating PI of rogaratinib/atezolizumab trial; consultant, trial open at my institution: Bayer; Financial Interests, Personal and Institutional, Invited Speaker, EV-201, EV- 103; consultant, trial open at my institution: Seagen; Financial Interests, Personal and Institutional, Invited Speaker, EV-301, consultant, trial open at my institution: Astellas; Financial Interests, Institutional, Invited Speaker, Consultant, PI of trial, trial open at my institution: AstraZeneca; Financial Interests, Institutional, Invited Speaker, PI of IMVIGOR210 (still open at my institution): Genentech; Financial Interests, Institutional, Invited Speaker, Investigator initiated trial at my institution: QED; Non-Financial Interests, Leadership Role, Bladder Cadre leader for Alliance (NCTN): Alliance for Clinical Trials in Oncology. M. Milowsky: Financial Interests, Personal, Advisory Board: Loxo/Lilly; Financial Interests, Personal, Other, Co-Editor-in-Chief, Clinical Genitourinary Cancer: Elsevier; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Stocks/Shares: Pfizer, Merck, Gilead Sciences; Financial Interests, Institutional, Invited Speaker: Merck, Roche/Genentech, Bristol-Myers Squibb, Mirati Therapeutics, Incyte, Seagen, G1 Therapeutics, Alliance Foundation Trials, Alliance for Clinical Trials in Oncology, Clovis Oncology, Arvinas, Regeneron. C. Ramamurthy: Financial Interests, Advisory Board: Seagen; Financial Interests, Speaker’s Bureau: Gilead. N. Mar: Financial Interests, Speaker’s Bureau: Seagen, Astellas Pharma. R.R. McKay: Financial Interests, Advisory Board: Janssen, Novartis, Tempus, Exelixis, Pfizer, Bristol-Myers Squibb, Astellas Medivation, Dendreon, Bayer, Sanofi, Merck, Vividion Therapeutics, Calithera Biosciences, AstraZeneca, Myovant Sciences, Caris Life Sciences, Sorrento Therapeutics; Financial Interests, Funding: Pfizer, Bayer, Tempus. T. Friedlander: Financial Interests, Advisory Board: AbbVie, Dendreon, Dava Oncology, EMD Serono, Merck, Astellas Pharma, Foundation Medicine, Basilea; Financial Interests, Project Lead: Med BioGene; Financial Interests, Other, Travel Expenses: AstrtaZeneca/MedImmune, Genentech/Roche, Jounce Therapeutics; Financial Interests, Other, Honoria: EMD Serono, AstraZeneca/MedImmune, Astellas Scientific and Medical Affairs Inc; Financial Interests, Research Grant: Janssen, Seagen, Incyte, Bristol-Myers Squibb, Neon Therapeutics, Roche/Genetech. C. Ferrario: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bayer, Merck, Knights Therapeutics; Financial Interests, Institutional, Invited Speaker: Astellas, AstraZeneca, Lilly, Merck, Novartis, Roche - Genetech, Sanofi, Seattle Genetics, Sermonix, Zymeworks; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Bayer; Non-Financial Interests, Advisory Role: AstraZeneca, Knights Therapeutics, Merck. S. Bracarda: Financial Interests, Other, Travel Expenses: Astellas Pharma; Financial Interests, Other: Seagen. S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, pfizer, Exelixis, Corvus, Sanofi/ Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Calithera, Corvus, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. H. Moon: Financial Interests, Funding: Bristol-Myers Squibb, Amgen, Prometheus. D. Geynisman: Financial Interests, Personal, Advisory Board: Pfizer, Merck, Exelixis, Astellas, Genentech; Financial Interests, Institutional, Invited Speaker: Genentech, Merck, Harpoon, Seattle Genetics. D.P. Petrylak: Financial Interests, Advisory Role: Bayer, Exelixis, Pfizer, Roche, Astellas Pharma, AstraZeneca, Lilly, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Incyte, Janssen, Pharmacyclics, Seagen, Urogen pharma, Advanced Accelerator Applications, Ipsen, Bicycle Therapeutics, Mirati Therapeutics, Monopteros Therapeutics, Regeneron, Gilead Sciences; Financial Interests, Expert Testimony: Celgene, sanofi; Financial Interests, Stocks/Shares: Bellicum Pharmaceuticals, Tyme; Financial Interests, Funding: Progenics, Sanofi, Endocyte, Genentech, Merck, Astellas Medivation, Novartis, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Pfizer, Roche, Seagen, clovis Oncology, Bristol-Meyers Squibb, Advanced Accelerator Applications, Agensys, BioXCel Therapeutics, Eisai, Mirati Therapeutics, Replimune, Medivation, Gilead Sciences. D. Borchiellini: Financial Interests, Advisory Role: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Ipsen, Janssen-Cilag, MSD Oncology, Pfizer, Sanofi, Merck; Financial Interests, Other, Travel Expenses: Bristol-Myers Squibb, Janssen, Pfizer, Roche; Financial Interests, Funding: Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Infinity Pharmaceuticals, Janssen, MSD, Roche. E.F. Burgess: Financial Interests, Advisory Role: Johnson & Johnson; Financial Interests, Speaker’s Bureau: AstraZeneca, Exelixis; Financial Interests, Stocks/Shares: Exelixis, Becton Dickinson, Calithera Biosciences, Gilead Sciences, Medtronic, Macrogenics, Arvinas, Autolus; Financial Interests, Other, Honoraria: Exelixis, Janssen Oncology, Novartis, Pfizer, Merck; Financial Interests, Funding: Pfizer, Astellas Pharma. J.P. Maroto Rey: Financial Interests, Advisory Role: Astellas, Ipsen, Bristol-Myers Squibb. A. Carret: Financial Interests, Personal, Full or part-time Employment, Senior Medical Director in Clinical Development: Seagen; Financial Interests, Personal, Stocks/Shares, Stocks/Shares/ESPP: Seagen; Non-Financial Interests, Member, ASCO: Seagen; Non-Financial Interests, Member, SIOP: Seagen; Non-Financial Interests, Member, Histiocyte Society: Seagen. Y. Yu: Financial Interests, Stocks/Shares: Seagen; Financial Interests, Full or part-time Employment, Employee: Seagen. M.V. Guseva: Financial Interests, Stocks/Shares: Astellas Pharma. B. Homet Moreno: Financial Interests, Institutional, Full or part-time Employment: Merck Employee; Financial Interests, Institutional, Stocks/Shares: Merck. P.H. O'Donnell: Financial Interests, Stocks/Shares: Allergan; Financial Interests, Other, Honoraria: Genetech/Roche, Merck, Astellas Pharma, Seagen, Atheneum Partners, Health Advances, Janssen, Dedham Group, Pfizer, CLD, Axiom Healthcare Strategies, EMD Serono, IntrinsiQ Specialty Solutions, ISMIE; Financial Interests, Funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/MedImmune, Acerta Pharma, Janssen, Seagen, Bristol-Myers Squibb, Astellas Pharma; Financial Interests, Other, Travel Expenses: Seagen, Astellas, Genentech/Roche; Financial Interests, Other: Janssen, Janssen, Nektar, NIH, Dragonfly Therapeutics, G1 THerapeutics.
Invited Discussant LBA68 and LBA73
- Laurence Albiges (Villejuif, Cedex, France)
Q&A
- All Speakers (Lugano, Switzerland)
1447O - Phase II study of belzutifan plus cabozantinib as first-line treatment of advanced renal cell carcinoma (RCC): Cohort 1 of LITESPARK-003
- Jaime Merchan (Coral Gables, United States of America)
Abstract
Background
HIF-2α is constitutively activated in RCC and is a transcription factor of multiple oncogenic pathways including TGF-α, GLUT1, cyclin D1, CXCR4, and VEGF. VEGF, and its receptor, are key regulators of angiogenesis and are upregulated in RCC. Belzutifan, a first-in-class HIF-2α inhibitor, has shown antitumor activity and favorable safety in heavily pretreated advanced RCC. Cabozantinib, a multikinase inhibitor that targets VEGF, is approved for advanced RCC. We present the first data of the use of belzutifan plus cabozantinib for treatment-naive pts with advanced RCC (cohort 1) enrolled in the ongoing, open-label, phase 2 LITESPARK-003 study (NCT03634540).
Methods
Treatment-naïve pts with advanced clear cell RCC and ECOG PS of 0/1 received belzutifan 120 mg QD PO plus cabozantinib 60 mg QD PO. The primary end point was confirmed ORR (CR + PR) per RECIST v1.1 by investigator review. Secondary end points were DOR, PFS, OS, and safety.
Results
Of 35 pts enrolled in cohort 1, 10 (29%) discontinued treatment; primarily due to progressive disease (n=8; 23%). Median age was 64 years (range, 33-89) and most pts had an ECOG PS of 0 (n=21; 60%), and IMDC favorable risk (n=21; 60%). Median follow-up was 14.0 mo (range, 0.2-33.0). Confirmed ORR was 57% (2 CRs, 18 PRs) and 13 pts (37%) had a best response of SD. Median DOR was 28.6 mo (range, 1.7+ to 28.6); 13 pts remained in response for ≥6 mo. Median PFS was 30.3 mo (95% CI, 9.4 to not reached); the estimated 12-mo PFS rate was 67%. Median OS was not reached; the estimated 12-mo OS rate was 96%. By IMDC risk category, ORR was 62% in 21 pts with favorable risk and 50% in 14 pts with intermediate/poor risk. In all pts, the most common any grade treatment-related AEs were anemia (n=25; 71%) and diarrhea (n=25; 71%). Grade 3 treatment-related AEs occurred in 13 pts (37%), most commonly hypertension (n=4; 11%) and fatigue (n=3; 9%). There were no grade 4 or 5 treatment-related AEs. 1 pt (3%) discontinued cabozantinib due to an AE (abdominal abscess). No pt discontinued belzutifan due to an AE.
Conclusions
Belzutifan plus cabozantinib had manageable safety with promising antitumor activity in treatment-naïve pts with advanced clear cell RCC.
Clinical trial identification
NCT03634540 Release date: August 16, 2018.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Robert Steger, PhD and Matt Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network ($400): ORIEN; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk ($1000): UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association ($1300): France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC ($500.00): Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement ($432.00): Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Invited Speaker, unpaidhttps://www.accru.org/main/public/index.xhtml: ACCRU; Financial Interests, Personal, Invited Speaker, Unpaidhttps://kidneycan.org: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Nuscan ((not publicly traded)); Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Exelixis, AstraZeneca, Takeda, Tracon, Peloton; Financial Interests, Institutional, Invited Speaker: Roche, Surface Oncology, GSK; Financial Interests, Institutional, Funding, National co-chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Invited Speaker, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019-: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Other, Employee at DFCI. Please see https://www.dana-farber.org/ for mission statement (non-profit hospital). I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Professor at HMS, Please see https://hms.harvard.edu/ for mission statement (non-profit school): Harvard Medical School (HMS); Other, No financial interest. Institutional.Filed patents related to biomarkers of immune checkpoint blockers, and circulating free methylated DNA. No money made and some patents were abandoned: Filed patents. T. Bauer: Financial Interests, Personal and Institutional, Invited Speaker: Pfizer, Lilly, Bayer; Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Lilly, Bayer, AstraZeneca; Financial Interests, Personal and Institutional, Funding: Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer, Lilly, Bayer, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Speaker’s Bureau: Lilly, Bayer, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Lilly, Bayer, AstraZeneca, Bristol Myers Squibb. J. Merchan: Financial Interests, Personal, Advisory Board: Merck; Other, Institutional, Principal Investigator: Merck, Eisai, Genentech, Rubius Therapeutics, Trishula Therapeutics, Corvus Pharmaceuticals, BioNtech, Vyriad, Seattle Genetics, SillaJen, Exelixis; Other, Institutional, Research Grant: SillaJen. R. Figlin: Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Principal Investigator: Merck. A. Roy: Financial Interests, Institutional, Full or part-time Employment: Merck; Financial Interests, Institutional, Stocks/Shares: Merck. R. Perini: Financial Interests, Institutional, Full or part-time Employment: MSD; Financial Interests, Institutional, Stocks/Shares: MSD. D. Vickery: Financial Interests, Institutional, Full or part-time Employment: MSD. All other authors have declared no conflicts of interest.
1448O - Phase II KEYNOTE-B61 study of pembrolizumab (Pembro) + lenvatinib (Lenva) as first-line treatment for non-clear cell renal cell carcinoma (nccRCC)
- Laurence Albiges (Villejuif, Cedex, France)
Abstract
Background
In ccRCC, first-line pembro + lenva improved OS, PFS, and ORR vs sunitinib in the phase 3 KEYNOTE-581 study. In nccRCC, first-line pembro monotherapy showed promising antitumor activity in cohort B of the phase 2 KEYNOTE-427 study. We report the first results of KEYNOTE-B61, a single-arm, phase 2 study (NCT04704219) evaluating pembro + lenva as first-line treatment for nccRCC.
Methods
Adults with previously untreated advanced nccRCC and measurable disease per RECIST v1.1 received pembro 400 mg IV Q6W up to 18 cycles (∼2 y) + lenva 20 mg orally QD. Primary end point was confirmed ORR (CR + PR) per RECIST v1.1 by BICR; secondary end points were DOR, DCR (CR + PR + SD), PFS, OS, and safety. Efficacy was evaluated in treated pts who had the opportunity for ≥24 wk of follow-up. Safety was evaluated in all treated pts.
Results
Of 147 treated pts, 87 (59.2%), 26 (17.7%), and 19 (12.9%) had papillary, chromophobe, and unclassified histology, respectively; 15 pts had translocation (4.1%), medullary (0.7%), or other (5.4%) histology. As of January 31, 2022, median follow-up for pts who had the opportunity for ≥24 wk of follow-up (n=82) was 8.2 mo (range, 5.5-10.5). Of these 82 pts, confirmed ORR was 47.6% (95% CI, 36.4-58.9; 3 CRs [3.7%]; 36 PRs [43.9%]). DCR was 79.3% (95% CI, 68.9-87.4). Median DOR was not reached (range, 1.4+ to 7.2+ mo). ORR and DCR in histologic subgroups are shown in the table. The 6-month PFS rate was 72.3% (95% CI, 60.7-81.0) and the 6-month OS rate was 87.8% (95% CI, 78.5-93.2). In all treated pts (N=147), any grade treatment-related AEs (TRAEs) occurred in 127 pts (86.4%), most commonly hypertension (n=71; 48.3%), diarrhea (n=37; 25.2%), and hypothyroidism (n=37; 25.2%). Grade 3-4 TRAEs occurred in 51 pts (34.7%). No deaths occurred due to TRAEs.
Total N = 82 Papillary n = 51 Chromophobe n = 15 Unclassified n = 7 Translocation n = 5 Other n = 4 47.6 (36.4-58.9) 52.9 (38.5-67.1) 13.3 (1.7-40.5) 71.4 (29.0-96.3) 60.0 (14.7-94.7) 50.0 (6.8-93.2) 79.3 (68.9-87.4) 78.4 (64.7-88.7) 73.3 (44.9-92.2) 100.0 (59.0-100.0) 80.0 (28.4-99.5) 75.0 (19.4-99.4)
Conclusions
In this preliminary analysis, pembro + lenva showed promising antitumor activity and manageable safety in pts with advanced nccRCC. No new safety signals emerged with this combination.
Clinical trial identification
NCT04704219, Release date: January 11, 2021.
Editorial acknowledgement
Medical writing and/or editorial assistance was provided by Robert Steger, PhD, and Mallory Campbell, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Eisai Inc., Nutley, NJ, USA.
Disclosure
L. Albiges: Financial Interests, Institutional, Other, Consulting: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Pfizer, BMS, Ipsen, AVEO, AstraZeneca, MSD; Non-Financial Interests, Other, Clinical trial steering committee: Roche, Exelixis; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Other, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology (EAU); Non-Financial Interests, Other, Member of the Kidney Cancer Research Summit scientific committee 2021: Kidney Can; Other, Scientific Committee: BMS France. H.P. Gurney: Financial Interests, Personal, Advisory Board: Merck, Ipsen, Pfizer, MSD, Astellas, Parexel, BMS, AstraZeneca, Janssen, Eisai, Amgen. C. Suárez: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Ipsen, Pfizer, EUSA Pharma, Astellas Pharma, Merck Sharp & Dohme, Eisai; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Ipsen, Pfizer, Roche/Genentech, AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche, Ipsen; Financial Interests, Institutional, Research Grant: Astellas Pharma, Roche/Genentech, Exelixis, AstraZeneca, Bristol Myers Squibb, Pfizer, Novartis, Janssen Oncology, Calithera Biosciences, AB Science, Arog, AVEO, Bayer, SFJ Pharmaceuticals Group, Blueprint Medicines, Clovis Oncology, Boehringer Ingelheim, Cougar Biotechnology, Deciphera, GlaxoSmithKline, Incyte, Karyopharm Therapeutics, MedImmune, Nanobiotix, Millennium, Puma Biotechnology, Teva. M.A. Climent Duran: Financial Interests, Personal, Invited Speaker: BMS, MSD, Bayer, Pfizer, Merck, Astellas, Janssen, Ipsen, EUSA, Roche, Astra, Eisai; Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Pfizer, Merck, Astellas, Janssen, Ipsen, EUSA, Roche, Astra, Eisai. D. Pook: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme. T. Ferguson: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Funding: Merck, Roche, BMS. E. Gokmen: Financial Interests, Personal, Invited Speaker: BMS, Roche, Pfizer, AstraZeneca, Novartis, Eli Lilly, Astellas, Janssen, Gilead, Amgen, Abdi Ibrahim, Mustafa Nevzat, Gen Ilac; Financial Interests, Personal, Advisory Board: BMS, Roche, Pfizer, AstraZeneca, Novartis, Eli Lilly, Astellas, Janssen, Gilead, Amgen, Abdi Ibrahim, Mustafa Nevzat, Gen Ilac. L. Lacombe: Non-Financial Interests, Institutional, Principal Investigator: CHU de Quebec-Université Laval. C. Gedye: Financial Interests, Institutional, Advisory Board: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Invited Speaker: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Other, Consulting: Merck EMD Serono, MSD, BMS, Astellas, Pfizer, AstraZeneca, Ipsen; Financial Interests, Institutional, Advisory Role: Limbic; Financial Interests, Institutional, Other, Travel support: BMS, Astellas, MSD; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Amgen, Merck Sharp & Dohme; Non-Financial Interests, Institutional, Other, Consulting: Novotech-CRO PTY; Non-Financial Interests, Institutional, Advisory Role: ANZUP Cancer Trials Group, COGNO, Mark Hughes Foundation, International Kidney Cancer Consortium. R. Perini: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. M. Sharma: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck, Regeneron. C. lI: Financial Interests, Personal, Full or part-time Employment: Merck. C. Lee: Financial Interests, Personal and Institutional, Advisory Board: BMS, Eisai, Exelixis, Merck, Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: BMS, Eisai, Exelixis, Merck, Pfizer; Financial Interests, Institutional, Principal Investigator: Calithera, Eli Lilly; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Invited Speaker: AiCME, Intellisphere, Research to Practice. All other authors have declared no conflicts of interest.
Invited Discussant 1447O and 1448O
- Andre P. Fay (Porto Alegre, Brazil)
Q&A
- All Speakers (Lugano, Switzerland)