All times are listed in CEST (Central European Summer Time)
- Karin Jordan (Potsdam, Germany)
- Florian Lordick (Leipzig, Germany)
LBA4 - Adjuvant nivolumab plus ipilimumab (NIVO+IPI) vs placebo (PBO) for localized renal cell carcinoma (RCC) at high risk of relapse after nephrectomy: Results from the randomized, phase III CheckMate 914 trial
- Robert J. Motzer (New York, United States of America)
Abstract
Background
CheckMate 914 (NCT03138512) is a phase III, randomized, double-blind, multicenter, 2-part trial evaluating NIVO+IPI vs PBO (part A) or NIVO monotherapy vs NIVO+IPI vs PBO (part B) in mutually exclusive patients (pts) with localized RCC at high risk of post-nephrectomy relapse. We report the primary analysis for part A of this trial.
Methods
CheckMate 914 key inclusion criteria: radical or partial nephrectomy with negative surgical margins > 4 and ≤ 12 weeks before randomization; predominant clear cell histology; pathological TNM stage T2a (grade [G] 3 or 4) N0M0, T2b (any G) N0M0, T3 (any G) N0M0, T4 (any G) N0M0, or any T (any G) N1M0; and no clinical/radiological evidence of residual disease or distant metastases. Pts were randomized 1:1 to NIVO 240 mg Q2W (× 12 doses) + IPI 1 mg/kg Q6W (× 4 doses) or equivalent PBO for 24 weeks or until disease recurrence/unacceptable toxicity. Stratification factors: TNM stage and type of nephrectomy. Primary endpoint: disease-free survival (DFS) per blinded independent central review; secondary endpoints include overall survival and safety.
Results
816 pts were randomized to NIVO+IPI (n = 405) vs PBO (n = 411). With 37.0 months of median follow-up (range, 15.4–58.0), the primary efficacy endpoint of DFS was not met (HR, 0.92; 95% CI, 0.71–1.19;
Conclusions
The CheckMate 914 trial of NIVO+IPI vs PBO in pts with localized RCC at high risk of relapse after nephrectomy did not meet the primary endpoint of DFS. Safety of NIVO+IPI was consistent with its known profile in advanced RCC, although the rate of discontinuation due to treatment-related AEs was higher with adjuvant NIVO+IPI vs PBO in this trial.
Clinical trial identification
NCT03138512.
Editorial acknowledgement
Professional medical writing assistance was provided by Richard Daniel, PhD, of Parexel, funded by Bristol Myers Squibb.
Legal entity responsible for the study
Bristol Myers Squibb.
Funding
Bristol Myers Squibb.
Disclosure
R.J. Motzer: Financial Interests, Personal, Advisory Board: AstraZeneca, Aveo, Aveo Pharmaceuticals, Eisai, EMD Serono, Exelixis, Genentech/Roche, Incyte, Lilly Oncology, Merck, Novartis, Pfizer; Financial Interests, Personal, Coordinating PI, funding for trial conduct from sponsor to my employer MSKCC: Aveo, BMS, Eisai, Exelixis, Genentech/Roche, Merck, Pfizer. V. Gruenwald: Financial Interests, Personal, Advisory Board: Apogepha, AstraZeneca, BMS, Debiopharm, Eisai, EUSA Pharm, Merck Serono, MSD, Nanobiotix, Oncorena, PCI Biotech, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, BMS, Eisai, Ipsen, Janssen-Cilag, Merck Serono, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Stocks/Shares: AstraZeneca, BMS, MSD, Seattle Genetics; Financial Interests, Institutional, Research Grant: BMS, Ipsen, MSD; Non-Financial Interests, Personal, Steering Committee member: BMS; Financial Interests, Personal and Institutional, Steering Committee member: Eisai, Novartis; Non-Financial Interests, Institutional, Steering Committee member: Ipsen; Non-Financial Interests, Personal, Research Grant: Pfizer; Non-Financial Interests, Personal, Trial Chair: PharmaMar. Y. Tomita: Financial Interests, Personal, Invited Speaker: Astellas, BMS, Merck, Ono; Financial Interests, Institutional, Research Grant: Chugai, Ono; Non-Financial Interests, Advisory Board: Eisai, Ono. S. Buti: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Ipsen, MSD, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Ipsen, MSD, Novartis; Financial Interests, Personal, Expert Testimony: MSD, Pierre-Fabre; Non-Financial Interests, Institutional, Local PI: AstraZeneca, BMS, Ipsen; Non-Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Institutional, Research Grant: Novartis; Non-Financial Interests, Member of the panel for kidney cancer guidelines: AIOM (Italian Association of Medical Oncology); Non-Financial Interests, Member and Coordinator of the rate tumors group: Meet-URO group (Italian Network for Research in Urologic Oncology). P. Barthelemy: Financial Interests, Personal, Research Grant: BMS, Ipsen, MSD, Pfizer, AstraZeneca, Janssen; Financial Interests, Personal, Consulting fees: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Amgen; Financial Interests, Personal, Speaker’s Bureau: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Bayer, Sanofi, Seagen, Novartis; Financial Interests, Personal, Travel support: BMS, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Sanofi, Seagen, Novartis. J.C.H. Goh: Financial Interests, Personal, Advisory Board, Prior member of the BMS RCC Advisory Board: BMS; Financial Interests, Personal, Advisory Board, Uterine Cancer Advisory Board: GSK; Financial Interests, Personal, Chairing RCC meeting: Ipsen; Financial Interests, Personal, Invited Speaker, Speaking @ MSD sponsored event on Gynaecological cancer: MSD; Financial Interests, Personal, Asia-Pacific Advisory Board member for prostate cancer: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Private Cancer Centres in Australia: ICON Cancer Centres; Non-Financial Interests, Institutional, Funding, Funding for phase II metastatic cervical cancer trial: BeiGene; Financial Interests, Principal Investigator, local PI for CheckMate-914, CheckMate-9KD Trial, CheckMate-7DX & CheckMate-9ER trials: BMS. J. Lattouf: Financial Interests, Personal, Advisory Board, Regional consultation group on bladder cancer (Québec): BMS; Financial Interests, Personal, Advisory Board, Assessment of prostate cancer practices: Knights; Financial Interests, Institutional, Invited Speaker, A presentation for community urologists about salvage therapy inprostate cancer: Tersera; Financial Interests, Personal, Advisory Board, BCG use in bladder cancer: Verity; Financial Interests, Institutional, Other, Local PI Research fees for the BMS914 trial: BMS; Financial Interests, Member: AUA, Candian Uro-Oncology Group, Canadian Urological Associations. B. Escudier: Financial Interests, Personal, Advisory Board: Pfizer, BMS, Ipsen, Aveo, Eisai. S. George: Financial Interests, Personal, Advisory Board, Advisor/consultant: Aveo, Bayer, BMS, Corvus, Eisai, EMD Serono, Exelixis, Merck, Pfizer, QED Therapeutics, Sanofi/Genzyme, Seattle Genetics; Non-Financial Interests, Personal, Local PI: Agensys, Aravive, Aveo, Bayer, BMS, Calithera, Corvus, Eisai, Exelixis, Gilead, Merck, Novartis, Pfizer, Seattle Genetics, Surface Oncology. B. Shuch: Financial Interests, Personal, Advisory Board: Genentech, Merck; Personal, Consultant for new device testing: J&J; Financial Interests, Personal, Invited Speaker, for Welireg: Merck; Personal, Consulted on genomic testing in kidney cancer: Veracyte; Non-Financial Interests, Institutional, Research Grant, Research on CAR T target: Allogene; Non-Financial Interests, Institutional, Coordinating PI Research on microbiome: Rebiotix. B. Simsek: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. J. Spiridigliozzi: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. A. Chudnovsky: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. A. Bex: Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Principal Investigator, Steering Committee member: BMS,Roche Genentech; Financial Interests, Advisory Role: International Kidney Cancer Coalition, KCA. All other authors have declared no conflicts of interest.
LBA5 - Primary results of the phase III KEYNOTE-412 study: Pembrolizumab (pembro) with chemoradiation therapy (CRT) vs placebo plus CRT for locally advanced (LA) head and neck squamous cell carcinoma (HNSCC)
- Jean-Pascal Machiels (Brussels, Belgium)
Abstract
Background
Pembro is approved as monotherapy or in combination with chemotherapy for recurrent/metastatic HNSCC. The randomized, double-blind, phase 3 KEYNOTE-412 (NCT03040999) study investigated the efficacy and safety of pembro + CRT vs placebo + CRT in patients (pts) with LA-HNSCC.
Methods
Pts with newly diagnosed, pathologically proven, treatment-naive LA-HNSCC (T3–T4 [N0–N3] or any N2a–3 [T1–T4] larynx/hypopharynx/oral cavity/p16-negative oropharynx cancers and T4 or N3 p16-positive oropharynx cancer) who were eligible for definitive CRT were randomized (1:1) to pembro 200 mg Q3W + CRT (70Gy/35F + cisplatin 100 mg/m2 Q3W) followed by pembro or placebo Q3W + CRT followed by placebo. A pembro/placebo priming dose was given 1 wk before CRT, followed by 2 doses during CRT and 14 doses of maintenance therapy after CRT, for a total of 17 doses. Primary endpoint was EFS (Efficacy boundary, one-sided
Results
804 pts were randomized (402 pts in each arm). Overall, baseline characteristics were well balanced between arms. At data cutoff (May 31, 2022) for the final analysis, median time from randomization to data cutoff was 47.7 (range, 37.0-61.4) mo. There was a favorable trend toward improved EFS with adding pembro vs placebo to CRT (HR 0.83, *Per the statistical analysis plan, the OS difference would be tested only if there was a significant difference in EFS.
Pembro + CRT (N=402) Placebo + CRT (N=402) Median (95% CI), mo NR (44.7-NR) 46.6 (27.5-NR) HR (95% CI), 0.83 (0.68-1.03), EFS rate at 24 mo, % (95% CI) 63.2 (58.2-67.8) 56.2 (51.1-61.0) Median (95% CI), mo NR (NR-NR) NR (NR-NR) HR (95% CI) 0.90 (0.71-1.15) OS rate at 24 mo, % (95% CI) 77.9 (73.5-81.7) 76.8 (72.4-80.7) HR (95% CI) 0.80 (0.64-1.00) 1.09 (0.56-2.11)
Conclusions
Pembro + CRT was associated with a favorable trend toward improved EFS vs placebo + CRT in patients with LA-HNSCC, but the difference did not reach statistical significance. No new safety signals were seen.
Clinical trial identification
NCT03040999.
Editorial acknowledgement
Medical writing assistance was provided by Yue Liu of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
J. Machiels: Financial Interests, Institutional, Advisory Board: Novartis, Pfizer, Roche, Debio, AstraZeneca, Innate, Nanobiotix, Bayer, Merck-Serono, Boerhinger-Ingelheim, BMS, Pfizer, Cue Pharma, Incyte, Janssen, Johnson & Johnson, ALX Oncology; Financial Interests, Institutional, Advisory Board, uncompensated: MSD; Financial Interests, Institutional, Invited Speaker: AstraZeneca, MSD, MSD, iTeos, eTheRNA, Pfizer, Ceylad, MSD, Novartis, KURA, Roche, Lilly, Boehringer, Sanofi-Aventis, Incyte, Bayer, Merck - Serono, Janssen, Johnson & Johnson, Amgen, AbbVie, GalxoSmithKline; Non-Financial Interests, Leadership Role, Chair: EORTC Head and Neck Group. Y. Tao: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Sponsor/Funding: Travel with MSD and Merck Serono. B. Burtness: Financial Interests, Personal, Invited Speaker: Fred Hutchinson Cancer Center, Massachusetts General Hospital, Stand Up to Cancer; Non-Financial Interests, Personal, Invited Speaker: National Cancer Institute, American Society of Clinical Oncology, Gordon Research Conference; Financial Interests, Personal, Speaker’s Bureau: I3 Health Clinical Education Alliance; Financial Interests, Personal, Advisory Board: Merck, Merck KgA, Debio, Kura, AstraZeneca, Genentech, Nektar, ALX Oncology, Actinium, Cue BioPharma, Janssen, Vaccinex; Financial Interests, Personal, Full or part-time Employment: Yale University; Financial Interests, Institutional, Research Grant: Merck, Cue, Vaccinex; Financial Interests, Personal and Institutional, Principal Investigator: National Institutes of Health Department of Defense Stand Up to Cancer Fanconi Anemia Research Foundation; Non-Financial Interests, Personal, Member: ECOG-ACRIN Oncology Research Group ASCO AACR ESMO; Financial Interests, Personal, Advisory Role: Mirati. M. Tahara: Financial Interests, Personal, Advisory Board: Merck Biopharma, Ono Pharma, Bristol Myers Squibb, MSD, Pfizer, Bayer, Lilly, Rakuten Medical, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Institutional, Invited Speaker: MSD, AstraZeneca, Ono Pharma, Novartis, Pfizer, Bristol-Myers Squibb, Loxo, GlaxoSmithKline, Lilly, Rakuten Medical; Financial Interests, Institutional, Research Grant: Bayer. D. Rischin: Non-Financial Interests, Institutional, Invited Speaker: Sanofi, MSD; Non-Financial Interests, Institutional, Advisory Board: MSD, Regeneron, BMS, GSK, Sanofi; Non-Financial Interests, Personal and Institutional, Principal Investigator: MSD, Merck KGgA, Regeneron, Sanofi, Roche, BMS, GSK, Kura, ALX Oncology; Financial Interests, Institutional, Sponsor/Funding: MSD, Merck KGgA, Regeneron, Sanofi, Roche, BMS, GSK, ALX Oncology. G.V. Alves: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Advisory Board: Merck Seromo, MSD; Financial Interests, Personal and Institutional, Principal Investigator: Roche, AstraZeneca, MSD, Bristol, Janssen, Merck Seromo, Beigene, GSK. Y. Pointreau: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD BMS. S. Laban: Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Speaker’s Bureau: Merck Sharp & Dohme, Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board: Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme; Financial Interests, Institutional, Principal Investigator: ISA Pharmaceuticals. R. Greil: Financial Interests, Personal, Funding: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen, BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Research Grant: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo; Financial Interests, Personal, Sponsor/Funding: Roche, Amgen, Janssen, AstraZeneca, Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo. M. Burian: Financial Interests, Personal, Advisory Board: MSD Austria, BMS Austria. M. Hetnal: Financial Interests, Personal and Institutional, Principal Investigator: Rydygier Memorial Hospital in Krakow. L.F. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck Serono, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics e GSK.; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La roche ltd, IRX Therapeutics, Medpace, Merck–Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Buran. R. Swaby: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. B. Gumuscu: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. B. Bidadi: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. L.L. Siu: Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Roche, Oncorus, Seattle Genetics, Voronoi, Arvinas, Tessa, Navire, Relay Therapeutics, Janpix, Amgen, Marengo, InterRNA, Medicenna, Hoopika, Coherus; Financial Interests, Personal, Spouse is co-founder: Treadwell Therapeutics; Financial Interests, Personal, Stocks/Shares, Spouse has stock ownership: Agios; Financial Interests, Institutional, Invited Speaker: Novartis, Bristol-Myers Squibb, Pfizer, Boerhinger-Ingelheim, GlaxoSmithKline, Roche/Genentech, AstraZeneca, Merck, Astellas, Bayer, Amgen, Symphogen, Intensity Therapeutics, Shattucks, EMD Serono; Non-Financial Interests, Advisory Role: ICR. All other authors have declared no conflicts of interest.
LBA6 - Neoadjvuant versus adjuvant pembrolizumab for resected stage III-IV melanoma (SWOG S1801)
- Sapna Patel (Houston, United States of America)
Abstract
Background
Adjuvant therapy (AT) is currently considered for resected stage IIB-III melanoma and selected patients with resected stage IV melanoma. AT for melanoma is anti-PD-1 or targeted therapy in the presence of a
Methods
SWOG S1801 is a randomized phase II study of AT versus NAT with pembrolizumab (PEM, NCT03698019). Patients with histologically confirmed, measurable, clinically detectable and resectable Stage IIIB-IV cutaneous, acral and mucosal melanomas without brain metastasis were randomized 1:1 to AT (upfront surgery followed by 18 doses of PEM 200 mg IV q3w) or NAT (3 doses of preoperative PEM, surgery and 15 doses of adjuvant PEM q3w). Radiation therapy was allowed after surgery. The primary endpoint was event-free survival (EFS) measured from the date of randomization to the date of first protocol-defined event: documented progression that renders the patient unable to receive planned protocol surgery, failure to begin AT within 84 days of surgery, relapse after surgery, or death due to any cause.
Results
A total of 313 patients were randomized: 154 to NAT and 159 to AT. With a median follow-up of 14.7 months, EFS was significantly higher on NAT compared to AT (one-sided log-rank
Conclusions
Using single-agent PEM, NAT improves EFS compared to AT in high-risk resectable melanoma.
Clinical trial identification
NCT03698019.
Legal entity responsible for the study
SWOG.
Funding
Merck & Co.
Disclosure
S. Patel: Financial Interests, Personal, Advisory Board: TriSalus, Cardinal Health, Castle Biosciences, Novartis; Financial Interests, Personal, Other, Consultant for educational materials: Advance Knowledge in Healthcare; Financial Interests, Personal, Advisory Board, Advisory Board and Corporate Day speaker (unbranded): Delcath; Financial Interests, Personal, Independent Data Monitoring Committee: Immunocore; Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Institutional, Invited Speaker: Provectus, Lvgen, Bristol Myers Squibb, InxMed, Foghorn Therapeutics, Ideaya, Novartis, Seagen, Syntrix Bio, TriSalus Life Sciences; Non-Financial Interests, Member: ASCO, AACR, International Society of Ocular Oncology, Society for Melanoma Research; Non-Financial Interests, Leadership Role: SWOG. M. Othus: Financial Interests, Personal, Consultant: Merck, Biosight; Financial Interests, Personal, Independent Data Safety Monitoring Committee Member: Celgene, Glycomimetics. V. Prieto: Financial Interests, Personal, Advisory Role: Castle Biosciences, Roche, Merck. M. Lowe: Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb. E. Buchbinder: Financial Interests, Personal, Advisory Board: Instilbio, Nektar, Novartis, BMS; Financial Interests, Institutional, Invited Speaker: Genentech, Partners therapeutics; Spouse employment: AstraZeneca. Y. Chen: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myer Squibb, Mirati; Financial Interests, Personal, Speaker Faculty: AstraZeneca, Bristol Myer Squibb, Amgen, Pizer, Takeda, Jazz Pharmaceutical, Guardant Health; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Merck, Ipsen, Bristol Myer Squibb, Amgen, Helsinn, EMD/Sorono. J. Hyngstrom: Financial Interests, Personal, Advisory Board, Advisory Board participant 12/2020 BMS/Nektar; Financial Interests, Institutional, Invited Speaker, Local PI for trial sponsored by Merck: Merck; Financial Interests, Personal and Institutional, Invited Speaker, PI for a single institution, investigator initiated clinical trial receiving partial institutional/research funding: BMS; Financial Interests, Personal and Institutional, Invited Speaker, PI on investigator initiated clinical trial receiving institutional/research funding support: Takara; Financial Interests, Invited Speaker, Local PI for clinical trial: Oncosec; Financial Interests, Invited Speaker, Local PI for trial: Viralytics; Financial Interests, Invited Speaker, Local PI for trial: Philogen; Financial Interests, Invited Speaker, Local PI for trial: Morphogenesis; Financial Interests, Invited Speaker, Local PI for trial: Iovance. C.D. Lao: Financial Interests, Institutional, Invited Speaker, Research Funding: BMS, Novartis, Genentech, Oncosec. T. Truong: Financial Interests, Institutional, Institutional Trial Support, Subinvestigator: Merck; Non-Financial Interests, Member and Active Member and State Affiliate President (California): ASCO. S. Chandra: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Pfizer, Sanofi Genzyme, Regeneron, EMD Serono, Exicure; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Novartis, EMD Serono, Regeneron, Pfizer, Exicure, Checkmate Pharmaceuticals, Merck; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squibb. A. Mangla: Financial Interests, Invited Speaker, Local PI for clinical study: BioAtla, Tracon Pharma; Financial Interests, Invited Speaker: Nektar Therapeutics, Trillium Therapeutics. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for Consulting: Amgen, Apexigen, AstraZeneca, Merck, Novartis, Sanofi, Vedanta; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, Immpact, ImaginAb, Immunesensor, Inspirna, Lutris, MapKure, Merus, PACT Pharma, Pluto, Synthekine, Tango; Financial Interests, Personal, Invited Speaker, Member of the Board of Directors: Arcus, Lutris, PACT Pharma; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, ImaginAb, Immpact, Immunesensor, Inspirna, Isoplexis, Lutris, MapKure, Merus, Pluto, Synthekine, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Kite-Gilead; Financial Interests, Personal, Invited Speaker: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol Myers Squibb. All other authors have declared no conflicts of interest.
LBA7 - Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study
- Myriam Chalabi (Amsterdam, Netherlands)
Abstract
Background
Neoadjuvant immunotherapy has shown promising responses in several cancer types. For colon cancer (CC), NICHE was the first neoadjuvant immunotherapy study to show pathologic responses in 100% of dMMR tumors. Importantly, disease-free survival (DFS) in patients (pts) with stage III dMMR CC is similar to that of pMMR pts, with 3-year recurrence risks of over 40% in high-risk (T4 and/or N2) stage III tumors despite adjuvant chemotherapy. Improving outcome for this patient population is urgently needed.
Methods
In the NICHE-2 study, pts with non-metastatic dMMR CC were treated with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) and underwent surgery ≤6 weeks of registration. The co-primary endpoints were safety (ITT) and 3-year DFS (PP). Secondary endpoints included major pathologic response (MPR) and complete response (pCR) rates. Pathologic response was defined as ≤50% residual viable tumor (RVT), and MPR as ≤10% RVT. Here we present safety and pathologic response data.
Results
A total of 112 pts were treated. Grade 3-4 immune-related adverse events were observed in 3 (3%) patients and only 3 pts experienced delay in surgery, meeting the safety primary endpoint. In the PP population (
Pathologic response MPR pCR 11 (92%) 9 (75%) 13 (100%) 10 (77%) 16 (94%) 10 (59%) 62 (95%) 43 (66%) 102 (95%) 72 (67%)
Conclusions
In NICHE-2 we confirm the previously reported pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in a large cohort of dMMR CC pts, with an MPR rate of 95%, including 67% pCR. The first survival data suggest a strong potential for neoadjuvant immunotherapy to become standard of care and allow further exploration of organ-sparing approaches.
Clinical trial identification
NL58483.031.16, EudraCT 016-002940-17.
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Bristol-Myers Squibb.
Disclosure
T.N. Schumacher: Financial Interests, Personal, Consultant: Third Rock Ventures; Financial Interests, Personal, Advisory Board: Allogene Therapeutics, Merus, Celsius Therapeutics; Financial Interests, Personal, Founder, Advisor: Asher Bio, Neogene Therapeutics; Financial Interests, Personal, Invited Speaker: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Third Rock Ventures, Allogene Therapeutics, Asher Bio, Merus, Neogene Therapeutics, Celsius Therapeutics. E.E. Voest: Financial Interests, Personal, Advisory Board, Hourly rate, to charity: Biogeneration Ventures; Financial Interests, Institutional, Advisory Board, Hourly rate, no compensation in 2019-2020: InteRNA; Financial Interests, Institutional, Invited Speaker, DRUP trial: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Clovis Oncology, Eisai, Ipsen, MSD, Novartis, Pfizer, GSK, Seattle Genetics; Financial Interests, Institutional, Invited Speaker, DRUP trial DRUG Access Protocol: Bayer, Roche; Financial Interests, Institutional, Invited Speaker, DRUG Access Protocol: Sanofi; Non-Financial Interests, Supervisory Board: HMF – Hartwig Medical Foundation; Non-Financial Interests, Principal Investigator, Senior Group Leader: Oncode Institute; Non-Financial Interests, Advisory Role, Editorial Board: JAMA Oncology; Non-Financial Interests, Leadership Role, Board of Directors: Cancer Core Europe. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Immunocore, Gadeta, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Editor-in-Chief IOTECH: ESMO, Editorial Board ESMO Open: ESMO; Editorial Board: Kidney Cancer. All other authors have declared no conflicts of interest.
Invited Discussant LBA4, LBA5, LBA6, LBA7 - The immunologist point of view
- Sherene Loi (Melbourne, Australia)
Invited Discussant LBA4, LBA5, LBA6, LBA7 - The medical oncologist point of view
- James Larkin (London, United Kingdom)
Q&A and discussion
- All Speakers (Lugano, Switzerland)