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Found 3 Presentations For Request "lba38"
LBA38 - Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study
- Domenica Lorusso (Rome, Italy)
Abstract
Background
Pembrolizumab (pembro) has shown efficacy in patients (pts) with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18(NCT04221945) assessed the efficacy and safety of pembro + concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer.
Methods
Eligible pts with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. The CCRT regimen included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose. Primary endpoints were PFS per RECIST version 1.1 by investigator and OS.
Results
1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At the protocol-specified first interim analysis (January 9, 2023, data cutoff), median follow-up was 17.9 mo (range, 0.9-31.0). Pembro + CCRT showed a statistically significant improvement in PFS vs pbo + CCRT. 24-mo PFS was 67.8% with pembro + CCRT vs 57.3% with pbo + CCRT; median PFS was not reached in either group (HR=0.70 [95% CI, 0.55-0.89; P=0.0020]); results were consistent across all prespecified subgroups. With only 103 events (42.9% maturity), the addition of pembro to CCRT showed a favorable trend in OS (HR=0.73 [95% CI, 0.49-1.07]); these data have not crossed the boundary of statistical significance. Grade ≥3 TRAE incidence was 67.0% in the pembro + CCRT group and 60.0% in the pbo + CCRT group.
Conclusions
Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with pbo + CCRT in pts with high-risk locally advanced cervical cancer and had a manageable safety profile. These data suggest pembro + CCRT can be considered as a new standard of care for this population.
Clinical trial identification
NCT04221945.
Editorial acknowledgement
Editorial assistance in the writing of the abstract was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.
Legal entity responsible for the study
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.
Funding
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A.
Disclosure
D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. Y. Xiang: Financial Interests, Institutional, Funding, Study funding: MSD; Financial Interests, Personal, Advisory Role, Member of Scientific Advisory Committee for MK3475-A18 study: MSD. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi, GSK; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Baxter Healthcare, GSK, Intuitive Surgical Inc., AstraZeneca & MSD, Olympus Europa, GSK, AstraZeneca & MSD, Olympus Europa; Financial Interests, Personal, Advisory Board, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Coordinating PI, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Coordinating PI, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Coordinating PI, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib.: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, Phase 3, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Coordinating PI, Phase 2b randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Coordinating PI, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd; Financial Interests, Institutional, Coordinating PI, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial.: Merck. M.H. Leiva Galves: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Roche, MSD, BMS. P. Ramos Elias: Financial Interests, Personal, Invited Speaker, Guest speaker at educational events: MSD, Asofarma, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board, Participation as a local expert on advisory board meetings: Bristol Myers Squibb, Asofarma, AstraZeneca; Financial Interests, Personal, Advisory Board, local expert on advisory board meetings: Pfizer; Financial Interests, Personal and Institutional, Local PI, Fees for conducting clinical studies: MSD, Roche Genentech, Zymeworks. A. Acevedo: Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dohme. J. Vizkeleti: Financial Interests, Institutional, Principal Investigator: Merck & Co., Inc.. A.J.P.D.S. Gomes: Financial Interests, Personal, Invited Speaker: Astellas, Bayer, Janssen, AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer, Janssen. F. Contreras Mejia: Financial Interests, Personal, Invited Speaker: MSD, BMS, GSK, Eli Lillly, AstraZeneca, Novartis; Financial Interests, Personal, Expert Testimony: MSD, Janssen, GSK, Eli Lilly, BMS; Financial Interests, Personal, Other, Meeting and travel support: MSD, Amgen. A. Reiss: Financial Interests, Personal, Advisory Board: MSD Israel. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. F. Zagouri: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Writing Engagement: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Funding: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Principal Investigator: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead; Financial Interests, Personal, Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, Merck, MSD, Novartis, Pfizer, Genesis- Pharma, Roche and Gilead. K. Li: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. K. Ussui Yamada: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. S. Toker: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. S. Pignata: Financial Interests, Personal, Advisory Board: Roche, AZ, MSD, Clovis, GSK, PharmaMar; Financial Interests, Institutional, Funding: Roche, MSD, Pfizer, AZ. L.R. Duska: Financial Interests, Personal, Advisory Board, Scientific advisory board: Aadi Bioscience; Financial Interests, Personal, Royalties, I write expert content for UpToDate: UpToDate; Financial Interests, Personal, Other, I serve on the Editorial Board: British Journal of Obstetrics and Gynecology; Financial Interests, Institutional, Research Grant, Merck has provided funding for investigator initiated trials to my institution: Merck; Non-Financial Interests, Advisory Role, Acted as an expert advisor for: Merck. All other authors have declared no conflicts of interest.
Invited Discussant LBA38
- Bradley J. Monk (Tucson, United States of America)
LBA35 - BNT211-01: Interim results from a repeat dose escalation study of CLDN6 CAR-T cells manufactured with an automated process ± a CLDN6-encoding CAR-T cell-amplifying RNA Vaccine (CARVac)
- John B. Haanen (Amsterdam, Netherlands)
Abstract
Background
Chimeric antigen receptor (CAR) T cells targeting CLDN6 ± CARVac showed promising activity against relapsed/refractory (r/r) CLDN6+ tumors (
Methods
BNT211-01 is recruiting patients (pts) with CLDN6-positive r/r solid tumours and no further treatment options. Following lymphodepletion, CAR T cells are flat dosed at 4 dose levels (DLs, 1×106 up to 2-5×108 CAR-T cells) ± repeat CLDN6 CARVac dosing (1×50 μg, then 100 μg doses). Primary endpoints are safety and tolerability. Additional endpoints are efficacy and pharmacokinetics.
Results
As of 24.07.2023, 38 pts primarily with ovarian cancer (n=14) and germ cell tumors (n=11) have been treated. Treatment related TEAEs ≥G3 were observed in 23 (61%) pts, including 20 (53%) pts with TEAEs related to CAR T cells. From 21 pts treated with the combination, 9 (43%) pts had TEAEs ≥G3 related to both IMPs, and 2 (10%) to CARVac. Related TESAEs have been observed in 8 pts (21%). DLTs occurred in 2 pts from different cohorts, G4 CRS at 5×108 CAR-T cells and G4 pancytopenia at 1×108, hence an MTD could not be determined. One death was assessed as treatment-related after the data cut-off. CRS was predominantly (95%) G1-2 and observed in 18 (47%) pts. 2 cases each of G1 ICANS and G1 hemophagocytic lymphohistiocytosis were reported (both 5%). Of 28 efficacy-evaluable patients, 9 pts (32%) had partial responses (PRs) and a further 9 had stable disease ([SD], unconfirmed overall response rate [ORR]: 32%, disease control rate [DCR]: 64%). Of 19 pts treated with ≥ 1x108 CAR T cells, 8 PRs and 8 SDs resulted in an ORR of 42% and a DCR of 84%. CAR-T expansion was dose dependent, with improved persistence by addition of CARVac.
Conclusions
CLDN6 CAR T cells ± CARVac demonstrated encouraging antitumor activity. Addition of CARVac improved CAR-T cell persistence. The safety profile in terms of CRS, ICANS and DLTs observed is in line with previously reported observations. We intend to present data on up to 42 pts, with a data cut-off of 10.09.2023.
Clinical trial identification
NCT04503278.
Editorial acknowledgement
Medical writing support was provided by Andrew Finlayson of BioNTech SE.
Legal entity responsible for the study
BioNTech SE.
Funding
BioNTech SE.
Disclosure
A. Mackensen: Financial Interests, Personal, Speaker, Consultant, Advisor: Miltenyi Biomedicine, KITE/Gilead, Novartis, BMS/Celegene; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Advisory Board: Ixaka. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, 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, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; 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; Other, Editorial Board ESMO Open: ESMO; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board: Kidney Cancer. W. Alsdorf: Financial Interests, Institutional, Local PI: BioNTech. C. Koenecke: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Novartis, Roche, Pierre Fabre, AbbVie, Sanofi-Aventis, Takeda, Kite, BMS, Medigene, Janssen, Amgen; Financial Interests, Institutional, Research Funding: BioNTech. E. Wagner-Drouet: Financial Interests, Personal, Speaker, Consultant, Advisor: Kite Gilead, BMS, Novartis; Financial Interests, Personal and Institutional, Coordinating PI: BioNTech. P. Borchmann: Financial Interests, Personal, Advisory Board: Takeda Oncology, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Miltenyi Biotech, Incyte; Financial Interests, Institutional, Coordinating PI: Takeda Oncology, Roche, Novartis, Merck Sharp & Dohme, Amgen, Miltenyi Biotech. D. Heudobler: Financial Interests, Personal, Research Funding: BMS, Janssen-Cilag; Financial Interests, Institutional, Research Funding: BioNTech. S. Klobuch: Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Local PI: Neogene. N. Kutsch: Financial Interests, Institutional, Research Funding: Gilead, AstraZeneca, BioNTech; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca. F. Müller: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Research Grant: Medimmune. C. Bokemeyer: Financial Interests, Personal, Advisory Board, advisory boards and speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Roche Pharma, AOK Germany; Financial Interests, Personal, Advisory Board: Bayer Healthcare, AstraZeneca, Oncology Drug Consult CRO, Jansen Cilag, BioNTech; Financial Interests, Personal, Advisory Board, Boards attended and lectures given: Sanofi Aventis; Financial Interests, Personal, Advisory Board, and lectures given: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, orgaistion for medical education: med update; Financial Interests, Institutional, Local PI, our department is involved in several clincal trials sponsored by industry and cooperative groups where we hold praticipants roles and local PI roles and PI roles: more than 95 clinical trials; Non-Financial Interests, Member of Board of Directors: DGHO, Northern German Society of Internal Medicine; Non-Financial Interests, Leadership Role: Hamburg Cancer Society, National Network of German Cancer Centers (DKH); Non-Financial Interests, Advisory Role, Board of DGHO Advisors: DGHO. A. Desuki: Financial Interests, Institutional, Research Funding: BioNTech. F. Lueke: Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Personal, Advisory Board: Janssen, MSD; Financial Interests, Institutional, Funding: Novartis. T. Ho: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech. K. Vemuri: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US. L. Preussner: Financial Interests, Personal, Financially compensated role: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. B. Rengstl: Financial Interests, Personal, Financially compensated role: BioNTech; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Project Lead: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. Ö. Türeci: Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Ownership Interest, CMO: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. U. Sahin: Financial Interests, Personal, Leadership Role, CEO: BioNTech; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Ownership Interest: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. All other authors have declared no conflicts of interest.