Found 1 Presentation For Request "1548P"
1548P - A phase Ia/Ib, dose-escalation/expansion study of the MDM2–p53 antagonist BI 907828 in patients (pts) with advanced/metastatic sarcoma
- Mrinal Gounder (New York, NY, United States of America)
Abstract
Background
The MDM2-p53 antagonist BI 907828 showed anti-tumour efficacy
Methods
NCT03449381 is a phase I study of BI 907828 monotherapy in pts with solid tumours evaluating two dosing schedules (Arm A: day 1 of 21-day cycles; Arm B: days 1 and 8 of 28-day cycles). Dose-limiting toxicities (DLTs) were assessed during Cycle 1, along with pharmacokinetics (PK) and anti-tumour activity.
Results
As of April 2, 2021, 54 pts (29 in Arm A, 25 in Arm B) had been enrolled, among whom 27 had advanced sarcomas. Pts received a median of 2 prior therapies (range, 0–11). Five patients experienced DLTs in arm A: one grade 3 nausea (45 mg), one grade 3 thrombocytopenia (TCP; 45 mg), one grade 3 enterocolitis (60 mg), one grade 4 neutropenia (80 mg), and one grade 4 TCP (80 mg). In arm B, 3 patients experienced DLTs: one grade 4 TCP (45 mg), one grade 4 neutropenia associated with grade 4 TCP (60 mg), and one grade 3 neutropenia (60 mg). The MTD was determined as 60 mg in Arm A and 45 mg in Arm B. The most common G 3/4 AEs were TCP (29.6%) and neutropenia (22.2%). Mean plasma exposures (Cmax and AUC0-inf) increased with dose. In the 27 pts with sarcoma, the disease control rate (DCR defined as CR + PR + SD) was 88.9%. Three of 7 pts with well-differentiated LPS achieved a PR (all were
Conclusions
BI 907828 showed a manageable safety profile, favourable PK, and early signs of anti-tumour activity in patients with sarcoma, especially
Clinical trial identification
NCT03449381.
Editorial acknowledgement
Medical writing assistance, supported financially by Boehringer Ingelheim Pharmaceuticals Inc., was provided by Jane Saunders of Ashfield MedComms, an Ashfield Health Company, during the preparation of this abstract.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
M. Gounder: Financial Interests, Personal, Other, consulting fees: Ayala; Financial Interests, Personal, Other, consulting fees: Bayer; Financial Interests, Personal, Other, consulting fees: Boehringer Ingelheim; Financial Interests, Personal, Other, consulting fees: Daiichi; Financial Interests, Personal, Other, consulting fees: Epizyme; Financial Interests, Personal, Other, consulting fees: Karyopharm; Financial Interests, Personal, Other, consulting fees: Springworks; Financial Interests, Personal, Other, consulting fees: Tracon; Financial Interests, Personal, Other, consulting fees: TYME/Syneos; Financial Interests, Personal, Other, consultation fees: Flatiron Health; Financial Interests, Personal, Other, consultation fees: Guidepoint; Financial Interests, Personal, Other, consultation fees: GLG; Financial Interests, Personal, Other, consultation fees: Medscape; Financial Interests, Personal, Other, consultation fees: More Health; Financial Interests, Personal, Other, consultation fees: Physicians Education Resource ; Financial Interests, Personal, Other, consultation fees: touchIME; Financial Interests, Personal, Royalties: UpToDate; Other, Personal, Other, uncompensated research: Foundation Medicine; Other, Personal, Other, uncompensated research: Rain; Other, Personal, Other, uncompensated research: Athenex; Financial Interests, Personal, Research Grant, Food and Drug Administration (R01 FD005105): Food and Drug Administration (R01 FD005105); Financial Interests, Personal, Research Grant, National Cancer Institute, National Institutes of Health (P30CA008748)—core grant (CCSG shared resources and core facility): National Cancer Institute, National Institutes of Health (P30CA008748)—core grant (CCSG shared resources and core facility). M.R. Patel: Financial Interests, Personal, Other, Consulting or advisory role: Pharmacyclics/Janssen; Financial Interests, Personal, Other, Consulting or advisory role: Pfizer/EMD Serono; Financial Interests, Personal, Speaker’s Bureau: Exelixis; Financial Interests, Personal, Speaker’s Bureau: Genentech/Roche; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Pharmacyclics; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Institutional, Research Grant: Acerta Pharma; Financial Interests, Institutional, Research Grant: ADC Therapeutics; Financial Interests, Institutional, Research Grant: Agenus; Financial Interests, Institutional, Research Grant: Aileron Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Bicycle Therapeutics; Financial Interests, Institutional, Research Grant: BioNTech AG; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Calithera Biosciences; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Checkpoint Therapeutics; Financial Interests, Institutional, Research Grant: CicloMed; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Cyteir; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: eFFECTOR Therapeutics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: EMD Serono; 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Financial Interests, Institutional, Research Grant: Artios; Financial Interests, Institutional, Research Grant: Treadwell Therapeutics; Financial Interests, Institutional, Research Grant: MabSpace Biosciences; Financial Interests, Institutional, Research Grant: IgM Biosciences; Financial Interests, Institutional, Research Grant: Puretech; Financial Interests, Institutional, Research Grant: Erasca, Inc. N. Yamamoto: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Chugai Pharma; Financial Interests, Personal, Other, Honoraria: Bristol-Myers Squibb Japan; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Lilly Japan; Financial Interests, Personal, Other, Honoraria: Sysmex; Financial Interests, Personal, Other, Consulting or advisory role: Eisai; Financial Interests, Personal, Other, Consulting or advisory role: Takeda; Financial Interests, Personal, Other, Consulting or advisory role: Otsuka; Financial Interests, Personal, Other, Consulting or advisory role: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting or advisory role: Cimic; Financial Interests, Personal, Other, Consulting or advisory role: Chugai Pharma; Financial Interests, Personal, Other, Research funding (received by immediate family member): Chiome Bioscience; Financial Interests, Personal, Other, Research funding (received by immediate family member): Otsuka; Financial Interests, Institutional, Research Grant: Chugai Pharma; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Astellas Pharma; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly Japan; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Kyowa Hakko Kirin; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: IQVIA; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon; Financial Interests, Institutional, Research Grant: Sumitomo Dainippon. T.M. Bauer: Financial Interests, Personal, Full or part-time Employment: Tennessee Oncology; Financial Interests, Institutional, Advisory Role: Ignyta; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Moderna Therapeutics; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Foundation Medicine; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Celgene; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Clovis Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: EMD Serono; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pharmacyclics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sysmex; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Institutional, OtherDaiichi Sankyo; Financial Interests, Institutional, Other, Research FResearch Fundingunding: MedPacto; Financial Interests, Institutional, OtherIncyte; Financial Interests, Institutional, OtherMirati Therapeutics; Financial Interests, Institutional, OtherMedImmune; Financial Interests, Institutional, OtherAbbvie; Financial Interests, Institutional, OtherAstraZeneca; Financial Interests, Institutional, OtherLeap Therapeutics; Financial Interests, Institutional, OtherMabVax; Financial Interests, Institutional, Other, ResearcResearch Fundingh Funding: Stemline Therapeutics; Financial Interests, Institutional, OtherMerck; Financial Interests, Institutional, OtherLilly; Financial Interests, Institutional, OtherGlaxoSmithKline; Financial Interests, Institutional, OtherNovartis; Financial Interests, Institutional, OtherPfizer; Financial Interests, Institutional, OtherGenentech/Roche; Financial Interests, Institutional, OtherDeciphera; Financial Interests, Institutional, OtherMerrimack; Financial Interests, Institutional, OtherImmunogen; Financial Interests, Institutional, OtherMillennium; Financial Interests, Institutional, OtherIgnyta; Financial Interests, Institutional, OtherCalithera Biosciences; Financial Interests, Institutional, OtherKolltan Pharmaceuticals; Financial Interests, Institutional, OtherPrincipa Biopharma; Financial Interests, Institutional, OtherPeleton; Financial Interests, Institutional, OtherImmunocore; Financial Interests, Institutional, OtherRoche; Financial Interests, Institutional, OtherAileron Therapeutics; Financial Interests, Institutional, OtherBristol-Myers Squibb; Financial Interests, Institutional, OtherAmgen; Financial Interests, Institutional, OtherModerna Therapeutics; Financial Interests, Institutional, OtherSanofi; Financial Interests, Institutional, OtherBoehringer Ingelheim; Financial Interests, Institutional, OtherAstellas Pharma; Financial Interests, Institutional, OtherFive Prime Therapeutics; Financial Interests, Institutional, OtherJacobio; Financial Interests, Institutional, OtherTop Alliance BioScience; Financial Interests, Institutional, OtherLoxo; Financial Interests, Institutional, OtherJanssen; Financial Interests, Institutional, OtherClovis Oncology; Financial Interests, Institutional, Other, ReseaResearch Fundingrch Funding: Takeda; Financial Interests, Institutional, OtherKaryopharm Therapeutics; Financial Interests, Institutional, OtherOnyx; Financial Interests, Institutional, OtherPhosplatin Therapeutics; Financial Interests, Institutional, OtherFoundation Medicine; Financial Interests, Institutional, OtherARMO BioSciences. A. Perez-Pitarch: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Geng: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Cheng: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim . M. Lahmar: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. P. Lorusso: Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: CytomX Therapeutics; Financial Interests, Personal, Advisory Role: Roche/Genentech; Financial Interests, Personal, Advisory Role: Halozyme; Financial Interests, Personal, Advisory Role: Five Prime Therapeutics; Financial Interests, Personal, Advisory Role: Agenus; Financial Interests, Personal, Advisory Role: Agios; Financial Interests, Personal, Advisory Role: Cybrexa Therapeutics; Financial Interests, Personal, Advisory Role: Sotio; Financial Interests, Personal, Advisory Role: Abbvie; Financial Interests, Personal, Advisory Role: Genmab; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Tyme; Financial Interests, Personal, Advisory Role: IQvia; Financial Interests, Personal, Advisory Role: Trial to Reduce IDDM in the Genetically at Risk (TRIGR); Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: ImmunoMet; Financial Interests, Personal, Advisory Role: Black Diamond Therapeutics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: QED Therapeutics; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Shattuck Labs; Financial Interests, Personal, Advisory Role: Astellas Pharma; Financial Interests, Personal, Advisory Role: Salarius Pharmaceuticals; Financial Interests, Personal, Advisory Role: Silverback Therapeutics; Financial Interests, Personal, Advisory Role: Macrogenics; Financial Interests, Personal, Advisory Role: Kyowa Kirin International; Financial Interests, Personal, Advisory Role: Kineta; Financial Interests, Personal, Advisory Role: Zentalis; Financial Interests, Personal, Advisory Role: Molecular Templates; Financial Interests, Personal, Advisory Role: Molecular Templates; Financial Interests, Personal, Advisory Role: ABL Bio; Financial Interests, Personal, Advisory Role: SK Life Sciences; Financial Interests, Personal, Advisory Role: ST Cube; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genentech; Financial Interests, Personal, Other, Honoraria: Five Prime Therapeutics; Financial Interests, Institutional, OtherGenentech. All other authors have declared no conflicts of interest.