Abstract CT112: Phase I open-label, multi-center study to evaluate the safety, tolerability, dosimetry, and preliminary activity of FXX489 ([<i>177</i>Lu]Lu-NNS309) in patients with pancreatic, lung, breast and colorectal cancers
Bibliographic record
Abstract
Abstract Background: Fibroblast activation protein (FAP) is a type II integral membrane glycoprotein, highly expressed on the cell surface of cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers and showing limited expression in normal tissues. Given this expression profile, FAP appears to be a promising target for radioligand therapy that has pan-cancer potential. [177Lu]Lu-NNS309 is a FAP-targeted radiopharmaceutical that shows improved tumor retention and demonstrates promising anti-tumor activity in translationally relevant preclinical models (e.g., PDAC, NSCLC) where FAP is expressed on CAFs. Methods: CFXX489A12101 (NCT06562192) is a first-in-human phase I, open-label, multi-center study of [177Lu]Lu-NNS309 in patients with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), breast cancer (BC), and colorectal cancer (CRC). The study includes a dose escalation part followed by a dose expansion part. Key eligibility criteria include prior treatment for locally advanced unresectable or metastatic disease and having all measurable lesions (per RECIST 1.1) showing [68Ga]Ga-NNS309 uptake on positron emission tomography/computed tomography (PET/CT). Patients who are eligible for treatment receive one dose of [177Lu]Lu-NNS309 on day 1 of each cycle. A 6-week and a 4-week dosing schedule will be explored. Dosimetry data will be obtained from patients in the dose escalation part after the first dose and will be used to calculate the cumulative radiation exposure. Dose escalation will be guided by a Bayesian hierarchical logistic regression model with overdose control (EWOC) principle, and assessment of all relevant data available from all dose levels including safety, tolerability, clinical dosimetry, pharmacodynamics, and preliminary efficacy. Once the recommended dose(s) (RD) and schedule(s) of [177Lu]Lu-NNS309 are determined, the expansion part may open and will include patients with locally advanced or metastatic PDAC (n∼20), locally advanced or metastatic NSCLC (n∼20), HR+/HER2- ductal BC (n∼15), HR+/HER2- lobular BC (n∼15), and triple negative BC (; n∼24).The primary objectives of the study are to evaluate the safety and tolerability of [177Lu]Lu-NNS309 and to identify the RD(s) and regimen(s) of [177Lu]Lu-NNS309 for further clinical evaluation. Secondary objectives of the study are to evaluate the preliminary anti-tumor activity of [177Lu]Lu-NNS309, characterize the pharmacokinetics of [177Lu]Lu-NNS309 in blood and urine, the radiation dosimetry for organs and tumor lesions, and to evaluate the safety and imaging properties of [68Ga]Ga-NNS309. Conclusion: The study is currently enrolling in the dose escalation part. Citation Format: Ravit Geva, Daniel Juneau, Shadi Abdar Esfahani, Cristiano Ferrario, Farshad Moradi, Amir Iravani, Jordi Ahnert, Ivan Manuel Victoria Ruiz, Thibaud Koessler, Aitana Calvo Ferrandiz, Bernard Doger de Speville, Patrick Flamen, Albiruni Razak, Desiree Deandreis, Laure Al-Mansour, Niklaus Schaefer, James Nagarajah, Hilde Nienhuis, Marco Maccauro, Angelina Filice, Jonathan Goldman, Ken Herrmann, Matthias Eiber, Alexander Drzezga, Martin Heuschkel, Jonathan McConathy, Johnson Geoffrey, Ephraim Parent, Yasutoshi Kuboki, Shizuka Origuchi, Xuan Mai Couillebault, Elisa Garcia Garayoa, Jayarama Naidu Roopa, Christopher Straub, Dominik Hainzl, Xinyu Chen, Fang Yang, Eirini Pectasides, Brandon Mancini. Phase I open-label, multi-center study to evaluate the safety, tolerability, dosimetry, and preliminary activity of FXX489 ([177Lu]Lu-NNS309) in patients with pancreatic, lung, breast and colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT112.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".