Abstract 620P
Background
MGC018 is an investigational ADC with a duocarmycin payload linked to an anti-B7-H3 monoclonal antibody. B7-H3 is expressed on multiple solid tumors with limited normal tissue expression. It is hypothesized that MGC018 may exert activity against B7-H3-expressing tumors with an acceptable safety profile. Phase I dose escalation was completed with two dose-limiting toxicities: one neutropenia grade 4 and one grade 3 fatigue of 72 hrs. There was 1 confirmed partial response in a melanoma patient, and 5/9 patients with 50% prostate-specific antigen (PSA) reduction in metastatic castration resistant prostate cancer (mCRPC).
Methods
The cohort expansion characterizes safety and preliminary efficacy with the recommended phase II dose of 3 mg/kg IV every 3 weeks. Patients with advanced mCRPC, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), squamous cell carcinoma of the head and neck (SCCHN), and melanoma are eligible for enrollment. Response is evaluated per RECIST v1.1 for all participants. mCRPC tumor response and PSA are evaluated using Prostate Cancer Working Group 2 criteria.
Results
The cohort expansion enrolled and dosed 49/80 patients as of May 3, 2021. mCRPC n=26/40, NSCLC, n=16/20, and TNBC n=7/20. At least 1 treatment emergent adverse event occurred in 43 patients (87.7%); the most common (≥10%) were neutropenia/neutrophil count decreased, fatigue, asthenia, palmar plantar erythrodysesthesia, and headache. Febrile neutropenia was not reported. Of 13 mCRPC patients with measurable disease, six were not yet evaluable, and seven had first 9-week imaging. Of the seven, four had reductions in target lesion sums of 13%, 21%, 27%, and 35% (unconfirmed partial response); 12 of the 13 remain on treatment. There are 11/22 evaluable patients with ≥50% PSA reduction.
Conclusions
Results to date have demonstrated a manageable safety profile with evidence of clinical activity by PSA and tumor responses in mCRPC. Enrollment is ongoing in advanced mCRPC, NSCLC, TNBC, SCCHN, and melanoma. Updated data will be provided.
Clinical trial identification
NCT03729596.
Editorial acknowledgement
Legal entity responsible for the study
MacroGenics, Inc.
Funding
MacroGenics, Inc.
Disclosure
E. Shenderov: Financial Interests, Personal, Stocks/Shares: LifeImmune; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Personal, Other, Patent pending in the field of allergy immunology and blood diagnostics: N/A. P.J. Wysocki: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Immunicom; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Immunicom; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Personal, Principal Investigator: Astellas; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Principal Investigator: Boehringer Ingelheim; Financial Interests, Personal, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Principal Investigator: Ipsen; Financial Interests, Personal, Principal Investigator: Immunicom; Financial Interests, Personal, Principal Investigator: Janssen; Financial Interests, Personal, Principal Investigator: Eli Lilly; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Merck; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Principal Investigator: Pierre Fabre; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Principal Investigator: Sanofi; Financial Interests, Personal, Principal Investigator: Servier. W. Xu: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Funding: Merck; Financial Interests, Personal, Other, Speaker Fees: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Speaker Fees: MSD; Financial Interests, Personal, Other, Speaker Fees: AstraZeneca. R. Ramlau: Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Roche; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Boehringer Ingelheim; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Novartis; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Amgen; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Pfizer; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: BMS; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Takeda; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Parexel; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: MSD; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: Merck; Financial Interests, Personal, Other, Speaker, Advisory Board, or Advisor: AstraZeneca. A.J. Weickhardt: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: BMS. A. Spira: Financial Interests, Personal, Stocks/Shares: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Institutional, Advisory Role: Array BioPharma; Financial Interests, Institutional, Advisory Role: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: ADC Therapeutics; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Arch Therapeutics; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: Astex Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: CytomX Therapeutics; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Gritstone Oncology; Financial Interests, Institutional, Funding: Ignyta; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Funding: LAM Therapeutics; Financial Interests, Institutional, Funding: Loxo; Financial Interests, Institutional, Funding: MacroGenics, Inc.; Financial Interests, Institutional, Funding: MedImmune; Financial Interests, Institutional, Funding: Newlink Genetics; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Plexxikon; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Trovagene. J. Powderly: Financial Interests, Institutional, Funding: Nucleus Inc.; Financial Interests, Institutional, Funding: MT Group; Financial Interests, Institutional, Funding: STEMCELL; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Institutional, Funding: InCyte; Financial Interests, Institutional, Funding: Top Alliance BioScience; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Funding: Corvus; Financial Interests, Institutional, Funding: Curis; Financial Interests, Institutional, Funding: RAPT Therapeutics; Financial Interests, Institutional, Funding: Alkermes; Financial Interests, Institutional, Funding: Arcus BioSciences; Financial Interests, Institutional, Funding: Tempest Therapeutics; Financial Interests, Institutional, Funding: Calico Life Sciences; Financial Interests, Institutional, Funding: Apros; Financial Interests, Institutional, Funding: Jounce; Financial Interests, Institutional, Funding: Atreca; Financial Interests, Institutional, Funding: BioBank Online; Financial Interests, Institutional, Funding: Sequenom; Financial Interests, Institutional, Funding: Replimmune; Financial Interests, Institutional, Funding: Engineered Pharma; Financial Interests, Institutional, Funding: CEM Corporation; Financial Interests, Institutional, Funding: Therapeutic BrainPower LLC; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Conjupro; Financial Interests, Institutional, Funding: Repertoire Medicines; Financial Interests, Personal, Advisory Role: TerumoBCT; Financial Interests, Institutional, Other, Joint IP: Atreca Inc.; Financial Interests, Institutional, Other, Developing IP for BioCytics and CBOI for cell therapies: BioCytics; Other, Personal, Other, Data Safety Monitoring Board/Advisory Board: AbbVie; Financial Interests, Personal, Stocks/Shares: BioCytics; Financial Interests, Personal, Stocks/Shares, Manager of CBOI PLLC: Carolina Biooncology Institute. E.S. Antonarakis: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Dendreon; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: ESSA; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Medivation; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Bristol-Myers Squibb; Financial Interests, Institutional, Funding: Celgene; Financial Interests, Institutional, Funding: Clovis Oncology; Financial Interests, Institutional, Funding: Dendreon; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Johnson & Johnson; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Funding: Tokai; Financial Interests, Personal, Other, Licensing/Royalties: Qiagen. S. Jang: Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Sun Biopharma; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb. J. Aragon-Ching: Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: EMD; Financial Interests, Personal, Advisory Board: Serono; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Immunomedics; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Astellas/Seattle Genetics. J. Shen: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Institutional, Funding: Arvinas. N.J. Vogelzang: Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Aravive; Financial Interests, Institutional, Principal Investigator: Arrowhead; Financial Interests, Institutional, Principal Investigator: Arvinas; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Invited Speaker: Aveo; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: Calithera; Financial Interests, Personal, Advisory Role: Cancer Expert Now; Financial Interests, Personal, Advisory Board: Caris; Financial Interests, Institutional, Principal Investigator: Clovis; Financial Interests, Institutional, Principal Investigator: Corvus; Financial Interests, Institutional, Principal Investigator: Dendreon; Financial Interests, Institutional, Principal Investigator: eFFECTOR; Financial Interests, Institutional, Principal Investigator: Eisai; Financial Interests, Institutional, Principal Investigator: Endocyte; Financial Interests, Institutional, Principal Investigator: Epizyme; Financial Interests, Institutional, Principal Investigator: ESSA; Financial Interests, Institutional, Principal Investigator: Exelexis; Financial Interests, Personal, Advisory Board: GeneCentric; Financial Interests, Institutional, Principal Investigator: Genentech; Financial Interests, Institutional, Principal Investigator: Immunomedics; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Principal Investigator: Kangpu; Financial Interests, Institutional, Principal Investigator: Kintor Suzhou; Financial Interests, Institutional, Principal Investigator: MacroGenics; Financial Interests, Institutional, Principal Investigator: Merck; Financial Interests, Institutional, Principal Investigator: Mirati; Financial Interests, Institutional, Principal Investigator: Modra; Financial Interests, Institutional, Principal Investigator: Myovant; Financial Interests, Institutional, Principal Investigator: Nektar; Financial Interests, Institutional, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Board: OnQuality Pharma; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Sanofi-Genzyme; Financial Interests, Institutional, Principal Investigator: Seattle Genetics; Financial Interests, Personal, Leadership Role, Vice Chair, GU committee: SWOG; Financial Interests, Institutional, Principal Investigator: Tolero; Financial Interests, Personal, Other, Section editor on prostate cancer: Up-To-Date; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Caris; Financial Interests, Personal, Speaker’s Bureau: Clovis; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: Corvus; Financial Interests, Personal, Advisory Board: Exelexis; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Board: Myovant; Financial Interests, Personal, Other, Legal defense advisor: Novartis; Financial Interests, Personal, Advisory Board: Sanofi-Genzyme; Financial Interests, Personal, Other, Legal defense advisor: Sanofi-Genzyme; Financial Interests, Personal, Speaker’s Bureau: Seattle Genetics. J. Cortés: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Cellestia; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Biothera Pharmaceutical; Financial Interests, Personal, Advisory Role: Merus; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Erytech; Financial Interests, Personal, Advisory Role: Athenex; Financial Interests, Personal, Advisory Role: Polyphor; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Merck Sharp&Dohme; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Leuko; Financial Interests, Personal, Advisory Role: Bioasis; Financial Interests, Personal, Advisory Role: Clovis Oncology; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Kyowa Kirin; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Samsung Bioepis; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Merck Sharp&Dohme; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Ariad Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Baxalta GMBH/Servier Affaires; Financial Interests, Institutional, Funding: Bayer Healthcare; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: F. Hoffman-LaRoche; Financial Interests, Institutional, Funding: Guardant Health; Financial Interests, Institutional, Funding: Merck Sharp&Dohme; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Piqur Therapeutics; Financial Interests, Institutional, Funding: Puma C; Financial Interests, Institutional, Funding: Queen Mary University of London; Financial Interests, Personal, Other, Stock, patents and intellectual property: MedSIR; Financial Interests, Personal, Other, Travel, accomodation, expenses: Roche; Financial Interests, Personal, Other, Travel, accomodation, expenses: Novartis; Financial Interests, Personal, Other, Travel, accomodation, expenses: Eisai; Financial Interests, Personal, Other, Travel, accomodation, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accomodation, expenses: Daiichi Sankyo. C. Bohac: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc.; Financial Interests, Personal, Stocks/Shares: MacroGenics, Inc. I. Lugowska: Financial Interests, Personal and Institutional, Principal Investigator: Roche; Financial Interests, Personal and Institutional, Principal Investigator: BMS; Financial Interests, Personal and Institutional, Principal Investigator: MSD; Financial Interests, Personal and Institutional, Principal Investigator: Janssen; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: Amgen; Financial Interests, Personal and Institutional, Principal Investigator: Pfizer; Financial Interests, Personal and Institutional, Principal Investigator: Boehringer Ingelhem; Financial Interests, Personal and Institutional, Principal Investigator: Novartis; Financial Interests, Personal and Institutional, Principal Investigator: Checkpoint; Financial Interests, Personal and Institutional, Principal Investigator: Agenus; Financial Interests, Personal and Institutional, Principal Investigator: MacroGenics; Financial Interests, Personal and Institutional, Principal Investigator: Incyte; Financial Interests, Personal and Institutional, Principal Investigator: Celon; Financial Interests, Personal and Institutional, Principal Investigator: Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Genmab; Financial Interests, Personal and Institutional, Principal Investigator: Loxo; Financial Interests, Personal and Institutional, Principal Investigator: Menarini; Financial Interests, Personal and Institutional, Principal Investigator: Blueprint; Financial Interests, Personal and Institutional, Principal Investigator: Odonate; Financial Interests, Personal and Institutional, Principal Investigator: Debio. All other authors have declared no conflicts of interest.