Abstract 1497P
Background
Several malignant solid tumors are characterized by high fibroblast activation protein alpha (FAPα) expression. FAPI-46 is a theranostic ligand for FAPα-directed PET imaging and subsequent radioligand therapy (RLT). We report efficacy and safety of 90Y-FAPI-46 RLT in patients with advanced sarcoma, pancreatic cancer (PDAC) and other cancer entities.
Methods
Up to four cycles of RLT were offered to patients with (a) progressive metastatic malignancy, (b) exhaustion of approved therapies, and (c) high FAPα expression, defined as SUVmax ≥10 in more than 50% of tumor lesions. Primary study endpoint was the disease control rate according to RECIST. Secondary endpoints included PET response rate according to PERCIST, overall survival, dosimetry and safety of FAPα-targeting RLT.
Results
In total, 21 patients (n=16/3/1/1 with sarcoma/PDAC/prostate/gastric cancer; 38% with ECOG PS ≥2) received n=47 90Y-FAPI-46 RLT cycles; n=16/21 (76%) patients underwent repeat RLT. By RECIST disease control was confirmed in n=8 of 21 patients (38%; 8 of 16 [50%] of evaluable patients), of which one had partial response and seven had stable disease after RLT. Disease control was associated with prolonged overall survival (log rank p=0.013). PERCIST response was noted in n=8 of 21 patients (38%; 8 of 15 [53%] of evaluable patients). Dosimetry was acquired for n=19 patients (90%). Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow and <0.14 Gy/GBq in liver and lung. Treatment-related grade 3/4 adverse events were observed in n=8 (38%) patients with thrombocytopenia (n=6) and anemia (n=6) being most prevalent.
Conclusions
FAPα-directed RLT using 90Y-FAPI-46 was safe, with radiation doses below critical range for organs at risk, and led to disease control in more than one third of patients, particularly patients with sarcoma. Discontinuation after the first cycle and a low rate of partial response require for future improvement of FAPα-directed RLT and should be assessed prospectively in patients with metastatic sarcoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Deutsche Forschungsgemeinschaft (DFG).
Disclosure
R.W. Hamacher: Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Invited Speaker: PharmaMar, Lilly; Financial Interests, Personal, Other, travel grant: PharmaMar, Lilly, Novartis. K.M. Pabst: Financial Interests, Personal, Funding: Bayer. L. Kessler: Financial Interests, Personal, Advisory Role: AAA, BTG; Financial Interests, Personal, Other, Personal fees: Sanofi. J. Ferdinandus: Financial Interests, Personal, Other, Personal fees: Eisai. M. Weber: Financial Interests, Personal, Speaker’s Bureau: Boston scientific. K. Lueckerath: Financial Interests, Personal, Advisory Role: SOFIE Bioscience, Enlaza Therapeutics. M.H.H. Schuler: Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Novartis, Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, Takeda; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb, AstraZeneca; Non-Financial Interests, , Principal Investigator, Member, Study Steering Board: Janssen. S. Bauer: Financial Interests, Personal, Advisory Board, Recurring Advisory Role since 2017 in the context of clinical trial development: Deciphera; Financial Interests, Personal, Advisory Board, Advisory role in the context of clinical trial development: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory role for clinical trial development: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board, Clinical trial developemnt: Daiichi-Sankyo; Financial Interests, Personal, Advisory Board, 2017: Plexxikon; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker, CME-related presentations: PharmaMar; Financial Interests, Personal, Advisory Board, Advisory role drug development: Roche; Financial Interests, Personal, Advisory Board, Advisory role drug development,: GSK; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Invited Speaker, PI for Enliven trial: Daiichii-Sankyo; Financial Interests, Institutional, Invited Speaker, Local PI for Avelumab Phase I trial: Roche; Financial Interests, Institutional, Invited Speaker, PI for Intrigue, Invictus and DCC-2618-Phase I trial; Lead PI for INtrigue trial, Scientific Committee for Invictus and Intrigue: Deciphera; Financial Interests, Institutional, Invited Speaker, PI for JGDJ trial Phase I Olaratumab plus Doxo/Ifos: Lilly; Financial Interests, Institutional, Invited Speaker, PI for Phase I trials cCGM097, HDM201, STI571-2103: Novartis; Financial Interests, Institutional, Invited Speaker, Local PI und national PI for Voyager and Navigator trial (BLU-285 / Avapritinib): Blueprint Medicines; Financial Interests, Institutional, Invited Speaker, PI (national) for Relatlimab (BMS-CA224-020): BMS; Financial Interests, Institutional, Invited Speaker, PI for IIT with ponatinib in GIST; research Grant (institutional for IIT): Incyte; Non-Financial Interests, , Advisory Role, Off-label committee: BfArm; Non-Financial Interests, , Invited Speaker, Founding Member of German Sarcoma Foundation: Deutsche Sarkomstiftung (German SarcomaFoundation). K. Herrmann: Financial Interests, Personal, Advisory Board: Bayer, Adacap/Novartis, Curium, Boston Scientific, GE Healthcare; Financial Interests, Personal, Invited Speaker: Sirtex, Siemens Healthineers, Sofie Biosciences, Theragnostics, Pharma 15; Financial Interests, Personal, Other, Consultant: Amgen; Financial Interests, Personal, Other, DMSB: ymabs; Financial Interests, Personal, Ownership Interest: Sofie Biosciences; Financial Interests, Personal, Stocks/Shares: Aktis Oncology; Non-Financial Interests, , Leadership Role, CEO, non-paid: Nuklearmedizin Interaktion GmbH; Non-Financial Interests, , Leadership Role, Chair Oncology&Theragnostics Committee: EANM. J.T. Siveke: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Immunocore, MSD, Roche, Servier; Financial Interests, Institutional, Funding: Bristol-Myers Squibb, Celgene, Roche, Eisbach; Financial Interests, Personal, Ownership Interest, and serves on the Board of Directors: Pharma15. W.P. Fendler: Financial Interests, Personal, Research Grant, Research: SOFIE Bioscience; Financial Interests, Personal, Speaker’s Bureau: Janssen, Bayer, AAA; Financial Interests, Personal, Advisory Role: Calyx, Bayer, Parexel; Financial Interests, Personal, Funding, Research: Bayer. All other authors have declared no conflicts of interest.