60MO - Theranostics in soft tissue sarcoma using a vascular disruption approach: Preliminary results of a proof-of-concept pilot study

Background

Patients with advanced soft tissue sarcomas (STSs) have very poor prognosis and systemic chemotherapy is the mainstay of therapy. Prostate-specific membrane antigen (PSMA) is highly expressed on the neovasculature of solid tumors, including 20% of STS lesions. PSMA theranostics using Gallium-68 PSMA-11 PET including contrast-enhanced CT (PSMA PET/ceCT) and Lutetium-177 ITG PSMA radioligand therapy (PSMA RLT) could be an interesting alternative for STS patients after standard therapy. Our single center, prospective clinical trial aims to evaluate feasibility and efficacy in advanced heavily treated patients with STS.

Methods

Patients with STS, progressing after standard therapy, ECOG 0-2 and a life expectancy of >3 months and adequate organ function qualify for study inclusion. Patients were screened by PSMA PET/CT and if uptake was relevant (higher than liver) were proposed to receive two standard cycles of 7400 MBq PSMA RLT in a classical six-week interval. Toxicity was noted using CTCAE v5.0 criteria, efficacy was measured by follow-up PSMA/ceCT to measure changes in PSMA uptake and according to RECIST 1.1. Secondary endpoints include dosimetry, progression-free survival (PFS), adverse events (AEs), overall survival (OS) and changes in immunological markers.

Results

Preliminary results show a high frequency of relevant PSMA uptake in sarcoma lesions of STS patients by PSMA PET/ceCT. Patients amenable for PSMA RLT did well tolerate two cycles of PSMA RLT. Efficacy analysis, toxicity and dosimetry data are currently being analyzed and will be presented at the congress.

Conclusions

PSMA theranostics show an unexpected high number PSMA positive in PSMA PET/ceCT in STS patients. The study is ongoing and final results will be presented at the congress. It might be that PSMA RLT could be a viable alternative for STS patients after exhausting standard treatment however larger trials are needed to better understand the real value of this approach in STS patients.

Clinical trial identification

NCT05420727.

Editorial acknowledgement

Legal entity responsible for the study

Nuclear Medicine CHUV.

Funding

The Alfred and Annemarie von Sick Grant (Zurich, Switzerland) and the Departments of Oncology and Nuclear Medicine & Molecular Imaging, Lausanne University Hospital (Lausanne, Switzerland).

Disclosure

A. Digklia: Financial Interests, Institutional, Invited Speaker: BMS, Roche; Financial Interests, Institutional, Advisory Board: AstraZeneca. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. G. Coukos: Financial Interests, Institutional, Advisory Board, CHF 2000 were provided to the CHUV but Dr Coukos did not receive any compensation.: Genentech; Financial Interests, Institutional, Advisory Board, CHF 2400 were provided to the CHUV but Dr Coukos did not receive any compensation.: AstraZeneca; Financial Interests, Institutional, Advisory Board, CHF 1500 were provided to the CHUV but Dr Coukos did not receive any compensation: EVIR; Financial Interests, Personal, Royalties, Dr Coukos has patents in the domain of antibodies and vaccines targeting the tumor vasculature as well as technologies related to T-cell expansion and engineering for T-cell therapy. Dr Coukos holds patents around TEM1 antibodies and receives royalties from the University of Pennsylvania regarding technology licensed to Novartis.: Novartis; Financial Interests, Personal, Royalties, Patent description: CAR T cells. Payment through the University of Pennsylvania: Tmunity Therapeutics; Financial Interests, Institutional, Invited Speaker, Patent description: Methods for expansion of lymphocytes.: Tigen Pharma; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche, BMS, Iovance Therapeutics, Tigen Pharma. All other authors have declared no conflicts of interest.